Alnylam Pharmaceuticals (ALNY) 10-K 14 Feb 19 2018 FY Annual report Financial data

Document and Entity Information

Document and Entity Information - USD ($)	12 Months Ended
	Dec. 31, 2018	Jan. 31, 2019	Jun. 29, 2018
Document And Entity Information [Abstract]
Document Type	10-K
Amendment Flag	false
Document Period End Date	Dec. 31, 2018
Document Fiscal Year Focus	2,018
Document Fiscal Period Focus	FY
Trading Symbol	ALNY
Entity Registrant Name	ALNYLAM PHARMACEUTICALS, INC.
Entity Central Index Key	1,178,670
Current Fiscal Year End Date	--12-31
Entity Well-known Seasoned Issuer	Yes
Entity Current Reporting Status	Yes
Entity Voluntary Filers	No
Entity Filer Category	Large Accelerated Filer
Entity Small Business	false
Entity Emerging Growth Company	false
Entity Shell Company	false
Entity Common Stock, Shares Outstanding		106,258,250
Entity Public Float			$ 9,819,826,967

CONSOLIDATED BALANCE SHEETS

CONSOLIDATED BALANCE SHEETS - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
Current assets:
Cash and cash equivalents	$ 420,146	$ 645,361
Marketable debt securities	662,803	1,045,257
Marketable equity securities	1,206
Accounts receivable, net	18,760	34,002
Inventory	24,068
Prepaid expenses and other current assets	73,713	40,120
Total current assets	1,200,696	1,764,740
Marketable debt securities		13,919
Property, plant and equipment, net	320,658	181,900
Restricted investments	44,825	30,000
Other assets	8,623	4,171
Total assets	1,574,802	1,994,730
Current liabilities:
Accounts payable	59,708	28,355
Accrued expenses	112,719	72,203
Deferred rent	3,571	1,988
Deferred revenue	3,496	41,705
Total current liabilities	179,494	144,251
Deferred rent, net of current portion	57,920	6,626
Deferred revenue, net of current portion	458	43,075
Long-term debt	30,000	30,000
Other liabilities	4,965	4,347
Total liabilities	272,837	228,299
Commitments and contingencies (Note 9)
Stockholders’ equity:
Preferred stock, $0.01 par value per share, 5,000,000 shares authorized and no shares issued and outstanding at December 31, 2018 and 2017
Common stock, $0.01 par value per share, 125,000,000 shares authorized; 101,177,007 shares issued and outstanding at December 31, 2018; 99,666,549 shares issued and outstanding at December 31, 2017	1,011	997
Additional paid-in capital	4,175,139	3,947,552
Accumulated other comprehensive loss	(33,213)	(34,433)
Accumulated deficit	(2,840,972)	(2,147,685)
Total stockholders’ equity	1,301,965	1,766,431
Total liabilities and stockholders’ equity	$ 1,574,802	$ 1,994,730

CONSOLIDATED BALANCE SHEETS (Pa

CONSOLIDATED BALANCE SHEETS (Parenthetical) - $ / shares	Dec. 31, 2018	Dec. 31, 2017
Statement Of Financial Position [Abstract]
Preferred stock, par value	$ 0.01	$ 0.01
Preferred stock, shares authorized	5,000,000	5,000,000
Preferred stock, shares issued	0	0
Preferred stock, shares outstanding	0	0
Common stock, par value	$ 0.01	$ 0.01
Common stock, shares authorized	125,000,000	125,000,000
Common stock, shares issued	101,177,007	99,666,549
Common stock, shares outstanding	101,177,007	99,666,549

CONSOLIDATED STATEMENTS OF COMP

CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS - USD ($) shares in Thousands, $ in Thousands		12 Months Ended
		Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Revenues:
Revenues		$ 74,908	$ 89,912	$ 47,159
Costs and expenses:
Cost of goods sold		1,802
Research and development	[1]	505,420	390,635	382,392
Selling, general and administrative	[1]	382,359	199,365	89,354
Total costs and expenses		889,581	590,000	471,746
Loss from operations		(814,673)	(500,088)	(424,587)
Other income (expense):
Interest income		29,262	12,236	8,308
Other income (expense)		4,173	(3,022)	6,171
Gain on litigation settlement		20,564
Total other income		53,999	9,214	14,479
Loss before income taxes		(760,674)	(490,874)	(410,108)
Provision for income taxes		(823)	0	0
Net loss		$ (761,497)	$ (490,874)	$ (410,108)
Net loss per common share — basic and diluted		$ (7.57)	$ (5.42)	$ (4.79)
Weighted-average common shares used to compute basic and diluted net loss per common share		100,590	90,554	85,596
Comprehensive loss:
Net loss		$ (761,497)	$ (490,874)	$ (410,108)
Unrealized gain (loss) on marketable securities, net of tax		1,220	(2,886)	(30,833)
Reclassification adjustment for realized loss (gain) on marketable securities included in net loss			1,894	(6,977)
Comprehensive loss		(760,277)	(491,866)	(447,918)
Product Revenues, Net
Revenues:
Revenues		12,535
Net Revenues from Collaborators
Revenues:
Revenues		$ 62,373	$ 89,912	$ 47,159
[1]	Stock-based compensation expenses included in operating costs and expenses are as follows: Research and development $80,509 $51,872 $42,946 Selling, general and administrative 77,243 40,947 32,582

CONSOLIDATED STATEMENTS OF CO_2

CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS (Parenthetical) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Stock-based compensation	$ 157,752	$ 92,819	$ 75,528
Research and Development
Stock-based compensation	80,509	51,872	42,946
Selling, General and Administrative
Stock-based compensation	$ 77,243	$ 40,947	$ 32,582

CONSOLIDATED STATEMENTS OF STOC

CONSOLIDATED STATEMENTS OF STOCKHOLDERS' EQUITY - USD ($) $ in Thousands	Total	Sanofi Genzyme	Common Stock	Common StockSanofi Genzyme	Additional Paid-in Capital	Additional Paid-in CapitalSanofi Genzyme	Accumulated Other Comprehensive Income (Loss)	Accumulated Deficit
Balance at Dec. 31, 2015	$ 1,264,714		$ 851		$ 2,506,197		$ 4,369	$ (1,246,703)
Balance (in shares) at Dec. 31, 2015			85,090,968
Exercise of common stock options, net of tax withholdings	11,608		$ 5		11,603
Exercise of common stock options, net of tax withholdings (in shares)			559,344
Issuance of common stock under other types of equity plans	3,648		$ 1		3,647
Issuance of common stock under other types of equity plans (in shares)			75,453
Issuance of common stock under equity plans, net of tax withholdings	(314)				(314)
Issuance of common stock under equity plans, net of tax withholdings (in shares)			10,549
Issuance of common stock, net of offering costs		$ 14,301		$ 2		$ 14,299
Issuance of common stock, net of offering costs (in shares)				205,030
Stock-based compensation expense related to equity-classified awards	74,182				74,182
Other comprehensive gain (loss), net of tax	(37,810)						(37,810)
Net loss	(410,108)							(410,108)
Balance at Dec. 31, 2016	920,221		$ 859		2,609,614		(33,441)	(1,656,811)
Balance (in shares) at Dec. 31, 2016			85,941,344
Exercise of common stock options, net of tax withholdings	80,546		$ 19		80,527
Exercise of common stock options, net of tax withholdings (in shares)			1,841,566
Issuance of common stock under other types of equity plans	5,907		$ 2		5,905
Issuance of common stock under other types of equity plans (in shares)			134,615
Issuance of common stock under equity plans, net of tax withholdings	(707)				(707)
Issuance of common stock under equity plans, net of tax withholdings (in shares)			11,523
Issuance of common stock, net of offering costs	1,139,625	$ 21,381	$ 114	$ 3	1,139,511	$ 21,378
Issuance of common stock, net of offering costs (in shares)			11,440,000	297,501
Stock-based compensation expense related to equity-classified awards	91,324				91,324
Other comprehensive gain (loss), net of tax	(992)						(992)
Net loss	(490,874)							(490,874)
Balance at Dec. 31, 2017	$ 1,766,431		$ 997		3,947,552		(34,433)	(2,147,685)
Balance (in shares) at Dec. 31, 2017	99,666,549		99,666,549
Cumulative effect adjustment from the adoption of new revenue standard	$ 68,210							68,210
Exercise of common stock options, net of tax withholdings	60,743		$ 12		60,731
Exercise of common stock options, net of tax withholdings (in shares)			1,267,728
Issuance of common stock under other types of equity plans	8,985		$ 1		8,984
Issuance of common stock under other types of equity plans (in shares)			108,539
Issuance of common stock under equity plans, net of tax withholdings	(769)		$ 1		(770)
Issuance of common stock under equity plans, net of tax withholdings (in shares)			134,191
Stock-based compensation expense related to equity-classified awards	158,642				158,642
Other comprehensive gain (loss), net of tax	1,220						1,220
Net loss	(761,497)							(761,497)
Balance at Dec. 31, 2018	$ 1,301,965		$ 1,011		$ 4,175,139		$ (33,213)	$ (2,840,972)
Balance (in shares) at Dec. 31, 2018	101,177,007		101,177,007

CONSOLIDATED STATEMENTS OF CASH

CONSOLIDATED STATEMENTS OF CASH FLOWS - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Cash flows from operating activities:
Net loss	$ (761,497)	$ (490,874)	$ (410,108)
Adjustments to reconcile net loss to net cash used in operating activities:
Depreciation, amortization and accretion, net	6,435	13,367	15,130
Stock-based compensation	157,752	92,819	75,528
Non-cash gain on litigation settlement	(10,000)
Charge for 401(k) company stock match	3,159	2,302	1,507
Fair value adjustments on marketable equity securities	(3,564)	1,894	(6,977)
Other		608
Changes in operating assets and liabilities:
Proceeds from landlord lease incentive for tenant improvements	25,350		2,145
Accounts receivable, net	15,242	(10,668)	(15,036)
Inventory	(22,645)
Prepaid expenses and other assets	(35,067)	(20,711)	(5,276)
Accounts payable	15,478	(4,939)	10,098
Accrued expenses and other	59,357	31,568	10,673
Deferred revenue	(12,616)	1,848	14,615
Net cash used in operating activities	(562,616)	(382,786)	(307,701)
Cash flows from investing activities:
Purchases of property, plant and equipment	(126,887)	(104,209)	(64,557)
Purchases of restricted investments	(14,825)		(150,000)
Purchases of marketable debt securities	(1,104,046)	(903,457)	(759,310)
Sales and maturities of marketable securities	1,518,703	597,305	1,116,458
Sale of restricted investments		120,000
Net cash provided by (used in) investing activities	272,945	(290,361)	142,591
Cash flows from financing activities:
Proceeds from exercise of stock options and other types of equity	68,939	84,142	14,127
Proceeds from issuance of common stock, net of offering costs		1,139,625
Proceeds from issuance of common stock to Sanofi Genzyme		21,381	14,301
Proceeds from issuance of long-term debt			150,000
Repayment of long-term debt		(120,000)
Payments for repurchase of common stock for employee tax withholding	(3,469)	(257)	(596)
Net cash provided by financing activities	65,470	1,124,891	177,832
Net (decrease) increase in cash, cash equivalents and restricted cash	(224,201)	451,744	12,722
Cash, cash equivalents and restricted cash, beginning of period	646,832	195,088	182,366
Cash, cash equivalents and restricted cash, end of period	422,631	646,832	195,088
Supplemental disclosure of cash flows:
Cash paid for interest	775	2,430	1,096
Cash paid for income taxes	1,066	114	111
Supplemental disclosure of noncash investing and financing activities:
Capital expenditures included in accounts payable and accrued expenses	33,274	8,176	33,153
Fair value of common stock received in the period for collaboration agreement in other assets	1,327	2,700
Receipt of common stock for exercises of stock options	$ 2,420	653	$ 1,260
Repurchase of common stock for employee tax withholding in accrued expenses		$ 450

CONSOLIDATED STATEMENTS OF CA_2

CONSOLIDATED STATEMENTS OF CASH FLOWS (Parenthetical) - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Statement Of Cash Flows [Abstract]
Cash and cash equivalents	$ 420,146	$ 645,361	$ 193,617
Restricted cash included in prepaid expenses and other current assets	$ 225
Restricted Cash and Cash Equivalents, Current, Asset, Statement of Financial Position [Extensible List]	us-gaap:PrepaidExpenseAndOtherAssetsCurrent	us-gaap:PrepaidExpenseAndOtherAssetsCurrent	us-gaap:PrepaidExpenseAndOtherAssetsCurrent
Restricted cash included in long-term other assets	$ 2,260	$ 1,471	$ 1,471
Restricted Cash and Cash Equivalents, Noncurrent, Asset, Statement of Financial Position [Extensible List]	us-gaap:OtherAssetsNoncurrent	us-gaap:OtherAssetsNoncurrent	us-gaap:OtherAssetsNoncurrent
Total cash, cash equivalents, and restricted cash shown in the consolidated statements of cash flows	$ 422,631	$ 646,832	$ 195,088

NATURE OF BUSINESS

NATURE OF BUSINESS	12 Months Ended
	Dec. 31, 2018
Organization Consolidation And Presentation Of Financial Statements [Abstract]
NATURE OF BUSINESS	1. NATURE OF BUSINESS We commenced operations on June 14, 2002 as a biopharmaceutical company seeking to develop and commercialize novel therapeutics based on RNA interference, or RNAi. We are committed to the advancement of our company strategy of building a multi-product, commercial biopharmaceutical company with a sustainable pipeline of RNAi therapeutics to address the needs of patients who have limited or inadequate treatment options. Since inception, ® During 2018, we also submitted regulatory applications for the approval of ONPATTRO in Japan, Canada and Switzerland, and we plan to make regulatory filings in additional markets in Europe and elsewhere throughout 2019. We are subject to risks common to companies in our industry including, but not limited to, uncertainties relating to conducting clinical research and development, the manufacture and supply of products for clinical and commercial use, obtaining and maintaining regulatory approvals and pricing and reimbursement for our products, market acceptance, managing global growth and operating expenses, availability of additional capital, competition, obtaining and enforcing patents, stock price volatility, dependence on collaborative relationships and third-party service providers, dependence on key personnel, potential litigation, product liability claims and government investigations.

SUMMARY OF SIGNIFICANT ACCOUNTI

SUMMARY OF SIGNIFICANT ACCOUNTING POLICIES	12 Months Ended
	Dec. 31, 2018
Accounting Policies [Abstract]
SUMMARY OF SIGNIFICANT ACCOUNTING POLICIES	2 . SUMMARY OF SIGNIFICANT ACCOUNTING POLICIES Basis of Presentation and Principles of Consolidation The accompanying consolidated financial statements reflect the operations of Alnylam and our wholly-owned subsidiaries. All intercompany accounts and transactions have been eliminated. Use of Estimates The preparation of financial statements in conformity with accounting principles generally accepted in the United States of America, or Liquidity Based on our current operating plan, we believe that our cash, cash equivalents and marketable debt securities at December 31, 2018, together with the cash we expect to generate from product sales and under our current alliances, will be sufficient to enable us to advance our Alnylam 2020 Concentrations of Credit Risk and Significant Customers Financial instruments that potentially expose us to concentrations of credit risk consist primarily of cash, cash equivalents and marketable debt securities. At December 31, 2018 and 2017, substantially all of our cash, cash equivalents and marketable debt securities were invested in money market funds, certificates of deposit, commercial paper, corporate notes, U.S. government-sponsored enterprise securities and U.S. treasury securities through highly rated financial institutions. Corporate notes may also include foreign bonds denominated in U.S. dollars. Investments are restricted, in accordance with our investment policy, to a concentration limit per issuer. In recent periods, our revenues have been generated primarily from collaborations with strategic partners, including Sanofi Genzyme, the specialty care global business unit of Sanofi, Vir Biotechnology, Inc., or Vir, and The Medicines Company, or MDCO. We began to record product revenues in the second half of 2018 following the approval of ONPATTRO by the The following table summarizes customers that represent greater than 10 percent of our consolidated total gross revenues for the periods indicated: Year Ended December 31, 2018 2017 2016 Sanofi Genzyme 58 % 61 % 68 % Vir Biotechnology 16 % * N/A Distributor A 13 % N/A N/A MDCO * 34 % 24 % * Represents 10 percent or less The following table summarizes customers with amounts due that represent greater than 10 percent of our gross accounts receivable balance, at the periods indicated: At December 31, 2018 2017 Distributor A 44 % N/A Sanofi Genzyme 29 % 39 % MDCO * 59 % * Represents 10 percent or less Fair Value Measurements The fair value is the price that would be received to sell an asset or paid to transfer a liability in an orderly transaction between market participants at the measurement date. In general, fair values determined by Level 1 inputs utilize quoted prices (unadjusted) in active markets for identical assets or liabilities. Fair values determined by Level 2 inputs utilize data points that are observable, such as quoted prices (adjusted), interest rates and yield curves. Fair values determined by Level 3 inputs utilize unobservable data points for the asset or liability, and include situations where there is little, if any, market activity for the asset or liability. The fair value hierarchy level is determined by the lowest level of significant input. Investments in Marketable Securities and Cash Equivalents We invest our excess cash balances in short-term and long-term marketable debt securities. We classify our investments in marketable debt securities as either held-to-maturity or available-for-sale based on facts and circumstances present at the time we purchased the securities. At each balance sheet date presented, we classified all of our investments in debt securities as available-for-sale. We report available-for-sale debt securities at fair value at each balance sheet date and include any unrealized holding gains and losses (the adjustment to fair value) in accumulated other comprehensive income (loss), a component of stockholders’ equity. At December 31, 2018, the balance in our accumulated other comprehensive loss was composed solely of activity related to our marketable debt securities and our investment in equity securities of Regulus Therapeutics Inc., or Regulus. Realized gains and losses are determined using the specific identification method and are included in other income (expense). We did not recognize any realized gains or losses from sales of our available-for-sale debt securities during the years ended December 31, 2018, 2017 or 2016, and as a result, did not reclassify any amount out of accumulated other comprehensive loss for the respective period related to our available-for-sale debt securities. If any adjustment to fair value reflects a decline in the value of the marketable debt securities, we consider all available evidence to evaluate the extent to which the decline is “other than temporary,” including our intention to sell and, if so, mark the investment to market through a charge to our consolidated statements of comprehensive loss. We did not record any impairment charges related to our marketable debt securities during the years ended December 31, 2018, 2017 or 2016. Our marketable debt securities are classified as cash equivalents if the original maturity, from the date of purchase, is 90 days or less, and as marketable debt securities if the original maturity, from the date of purchase, is in excess of 90 days. Our cash equivalents are generally composed of commercial paper, corporate notes, U.S. government-sponsored enterprise securities, U.S. treasury securities and money market funds. Upon the adoption of the new accounting standard, discussed below under the heading “Recent Accounting Pronouncements,” effective January 1, 2018, we measure marketable equity investments (except those accounted for under the equity method of accounting or those that result in consolidation of an investee), which have readily available prices, at fair value with changes in fair value recognized in other income (expense) on our consolidated statements of comprehensive loss During the second quarter of 2017, we sold all our remaining holdings in Regulus. We accounted for our investment in Regulus as an available-for-sale marketable equity security. We recognized $1.9 million of realized losses and $7.0 million of realized gains from sales of our Regulus available-for-sale securities as other income (expense) in our consolidated statement of comprehensive loss during the year ended December 31, 2017 and 2016, respectively. Intraperiod tax allocation rules require us to allocate our provision for income taxes between continuing operations and other categories of earnings, such as other comprehensive income. In periods in which we have a year-to-date pre-tax loss from continuing operations and pre-tax income in other categories of earnings, such as other comprehensive income, we must allocate the tax provision to the other categories of earnings. We then record a related tax benefit in continuing operations. Upon sales of our marketable equity securities, we apply the aggregate portfolio approach to recognize the related tax provision or benefit into income (loss) from continuing operations. As a result, the disproportionate tax effect remains in accumulated other comprehensive income (loss) as long as we maintain an investment portfolio. At December 31, 2018 and 2017, there was $32.8 million of accumulated other comprehensive loss, net of tax, recorded on our consolidated balance sheets related to our investment in Regulus. Accounts Receivable We record accounts receivable net of customer allowances for distribution services, prompt payment discounts and chargebacks based on contractual terms. As of December 31, 2018, we determined an allowance for doubtful accounts was not required based upon our review of contractual payment terms and individual customer circumstances. We have standard payment terms that generally require payment within approximately 30 to 50 days. Accounts receivable, net on our consolidated balance sheets also includes billed and unbilled collaboration receivables. Inventory Prior to initial regulatory approval, we expense costs relating to the production of inventory as research and development expenses on our consolidated statements of comprehensive loss in the period incurred, unless we believe regulatory approval and subsequent commercialization of the product candidate is probable and we expect the future economic benefit from sales of the product to be realized, at which point we capitalize the costs as inventory. Inventory is measured at the lower of cost or estimated net realizable value. We use a standard cost basis, which approximates average cost determined on a first-in, first-out basis. Inventory costs include all raw materials, direct conversion costs and overhead. Raw and intermediate materials that may be used for either research and development or commercial purposes are classified as inventory until the material is consumed or otherwise allocated for research and development. If the material is used for research and development, it is expensed as research and development once that determination is made. We capitalize inventory costs that are expected to be sold commercially once we determine there is a high probability that the inventory costs will be recovered through commercial sale based on the review of several factors, including (i) the likelihood that all required regulatory approvals will be obtained, (ii) the expected timing of validation of manufacturing processes in the associated facility (if not yet completed), (iii) the expected expiration of the inventory, (iv) logistical or commercial constraints that may impede the timely distribution and sale of the product, including transport requirements and reimbursement status, (v) the history of approvals of similar products or formulations, and (vi) potential legal challenges. We reduce our inventory to net realizable value for potentially excess, dated or obsolete inventory based on our quarterly assessment of the recoverability of our capitalized inventory. Through December 31, 2018, we had not identified any impairment of our capitalized inventory. Property, Plant and Equipment Property, plant and equipment are stated at cost, net of accumulated depreciation. Depreciation expense is recorded on a straight-line basis over the estimated useful life of the asset. Leasehold improvements are amortized over the shorter of the asset’s estimated useful life or the lease term. Construction in progress reflects amounts incurred for construction or improvements of property, plant or equipment that have not been placed in service. Costs of construction of certain long-lived assets include capitalized interest, which is amortized over the estimated useful life of the related asset. The cost and accumulated depreciation of assets retired or sold are removed from the respective asset category, and any gain or loss is recognized in our consolidated statements of comprehensive loss. The estimated useful lives of property, plant and equipment are as follows: Asset Category Useful Life Laboratory equipment 5 years Computer equipment and software 3-10 years Furniture and fixtures 5 years Leasehold improvements Shorter of asset life or lease term Land — Construction in progress — Estimated Liability for Development Costs We record accrued liabilities related to expenses for which service providers have not yet billed us with respect to products we have received or services that we have incurred, specifically related to ongoing pre-clinical studies and clinical trials. These costs primarily relate to third-party clinical management costs, laboratory and analysis costs, toxicology studies and investigator fees. We have multiple product candidates in concurrent pre-clinical studies and clinical trials at multiple clinical sites throughout the world. In order to ensure that we have adequately provided for ongoing pre-clinical and clinical development costs during the period in which we incur such costs, we maintain an accrual to cover these expenses. We update the estimate for this accrual on at least a quarterly basis. The assessment of these costs is a subjective process that requires judgment. Upon settlement, these costs may differ materially from the amounts accrued in our consolidated financial statements. Our historical accrual estimates have not been materially different from our actual costs. Revenue Recognition We began to record revenues from product sales in the third quarter of 2018 subsequent to the approval of ONPATTRO by the FDA in August 2018. Prior to the third quarter of 2018, all of our revenues were derived from collaboration agreements that we have entered into with leading pharmaceutical and life sciences companies, including Sanofi Genzyme and MDCO. The terms of our collaboration agreements may include consideration such as non-refundable license fees, funding of research and development services, payments due upon the achievement of clinical and pre-clinical performance-based development milestones, regulatory milestones, manufacturing services, sales-based milestones and royalties on product sales. On January 1, 2018, we adopted the new revenue standard, discussed below under the heading “Recent Accounting Pronouncements,” which amended revenue recognition principles and provides a single, comprehensive set of criteria for revenue recognition within and across all industries. Our adoption of the new revenue standard had a material impact on our consolidated financial statements, as discussed below under the heading “Recent Accounting Pronouncements.” This new revenue standard applies to all contracts with customers, except for contracts that are within the scope of other standards, such as leases, insurance, collaboration arrangements and financial instruments. The new revenue standard provides a five-step framework whereby revenue is recognized when control of promised goods or services is transferred to a customer at an amount that reflects the consideration to which the entity expects to be entitled in exchange for those goods or services. To determine revenue recognition for arrangements that we determine are within the scope of the new revenue standard, we perform the following five steps: (i) identify the contract(s) with a customer; (ii) identify the performance obligations in the contract; (iii) determine the transaction price; (iv) allocate the transaction price to the performance obligations in the contract; and (v) recognize revenue when (or as) we satisfy a performance obligation. We only apply the five-step model to contracts when collectability of the consideration to which we are entitled in exchange for the goods or services we transfer to the customer is determined to be probable. At contract inception, once the contract is determined to be within the scope of the new revenue standard, we assess whether the goods or services promised within each contract are distinct and, therefore, represent a separate performance obligation. Goods and services that are determined not to be distinct are combined with other promised goods and services until a distinct bundle is identified. We then allocate the transaction price (the amount of consideration we expect to be entitled to from a customer in exchange for the promised goods or services) to each performance obligation and recognize the associated revenue when (or as) each performance obligation is satisfied. Our estimate of the transaction price for each contract includes all variable consideration to which we expect to be entitled. Amounts are recorded as accounts receivable when our right to consideration is unconditional. We do not assess whether a contract has a significant financing component if the expectation at contract inception is that the period between payment by the customer and the transfer of the promised goods or services to the customer will be one year or less. We expense incremental costs of obtaining a contract as and when incurred if the expected amortization period of the asset that we would have recognized is one year or less or the amount is immaterial. At December 31, 2018, we had not capitalized any costs to obtain any of our contracts. Product revenues, net In the third quarter of 2018, following FDA approval in August 2018, we began to ship ONPATTRO in the U.S. to specialty pharmacies, or SPs, and a specialty distributor, or SD, referred to as our customers. Our U.S. customers subsequently resell ONPATTRO to health care providers. We also received approval from the EC in August 2018 and launched ONPATTRO in several countries in Europe during the fourth quarter of 2018, where we primarily sell to government-owned and supported customers, including hospitals. The following are the components of variable consideration related to product revenues. We record reserves, based on contractual terms, for these components related to product sold during the reporting period, as well as our estimate of product that remains in the distribution channel inventory at the end of the reporting period that we expect will be sold to qualified healthcare providers. On a quarterly basis, we will update our estimates and record any needed adjustments in the period we identify the adjustments. Chargebacks: We estimate obligations resulting from contractual commitments with the government and other entities to sell products to qualified healthcare providers at prices lower than the list prices charged to the SD who purchases ONPATTRO from us. The SD charges us for the difference between what the SD pays to us for the product and the selling price to the qualified healthcare providers. Rebates : We are subject to discount obligations under government programs, including Medicaid in the U.S. and similar programs in certain countries in Europe. We are also subject to potential rebates in connection with our value-based agreements with certain commercial payors. We record reserves for rebates in the same period the related product revenue is recognized, resulting in a reduction of ONPATTRO product revenues and a current liability that is included in accrued expenses on our consolidated balance sheet. Our estimate for rebates is based on statutory discount rates and expected utilization. Trade discounts and allowances: We provide customary invoice discounts on ONPATTRO sales to our customers for prompt payment and we pay fees for distribution services, such as fees for certain data that customers provide to us. We estimate our customers will earn these discounts and fees, and deduct these discounts and fees in full from gross ONPATTRO revenues and accounts receivable at the time we recognize the related revenues. Product returns: ONPATTRO may be returned if it is damaged, defective or expired, with “expired” defined as having three months or less to expiry or within three months past expiry. We estimate the amount of product that will be returned using a probability-weighted estimate, initially calculated based on a portfolio of data from similar products and industry experience for SP products. Based on the distribution model for ONPATTRO, contractual inventory limits with our customers, the price of ONPATTRO and limited contractual return rights, we believe there will be minimal ONPATTRO returns. We have recorded an initial refund liability for our estimate of ONPATTRO returns related to sales during the year ended December 31, 2018. We will update our estimated refund liability, on at least a quarterly basis, based on actual shipments of ONPATTRO subject to contractual return rights, changes in expectations about the amount of estimated refunds or actual returns, as data is known Other incentives: Other incentives include co-payment assistance we provide to patients with commercial insurance that have coverage and reside in states that allow co-payment assistance. We estimate the average co-payment assistance amounts for ONPATTRO based on expected customer demographics and record any such amounts within accrued expenses on our consolidated balance sheet. Revenues from Collaborators We recognize the transaction price allocated to upfront license payments as revenue upon delivery of the license to the customer and resulting ability of the customer to use and benefit from the license, if the license is determined to be distinct from the other performance obligations identified in the contract. we exercise judgment to assess the nature of the combined performance obligation to determine whether the combined performance obligation is satisfied (i) at a point in time, but only for licenses determined to be distinct from other performance obligations in the contract, or (ii) over time; and, if over time, the appropriate method of measuring progress for purposes of recognizing revenue from license payments. We evaluate the measure of progress each reporting period and, if necessary, adjust the measure of performance and related revenue recognition. Many of our collaboration agreements entitle us to additional payments upon the achievement of performance-based milestones. These milestones are generally categorized into three types: development milestones, which are generally based on the advancement of our pipeline and initiation of clinical trials; regulatory milestones, which are generally based on the submission, filing or approval of regulatory applications such as an NDA in the U.S.; and sales-based milestones, which are generally based on meeting specific thresholds of sales in certain geographic areas. For each collaboration that includes development milestone payments, we evaluate whether it is probable that the consideration associated with each milestone will not be subject to a significant reversal in the cumulative amount of revenue recognized. Amounts that meet this threshold are included in the transaction price using the most likely amount method, whereas amounts that do not meet this threshold are considered constrained and excluded from the transaction price until they meet this threshold. At the end of each subsequent reporting period, we re-evaluate the probability of a significant reversal of the cumulative revenue recognized for our milestones, and, if necessary, adjust our estimate of the overall transaction price. Any such adjustments are recorded on a cumulative catch-up basis, which would affect revenues from collaborators and loss in the period of adjustment. have not recognized any royalty revenue resulting from any of our agreements. The new revenue standard, which was adopted in January 2018, requires us to allocate the arrangement consideration on a relative standalone selling price basis for each performance obligation after determining the transaction price of the contract and identifying the performance obligations to which that amount should be allocated. The relative standalone selling price is defined in the new revenue standard as the price at which an entity would sell a promised good or service separately to a customer. If other observable transactions in which we have sold the same performance obligation separately are not available, we are required to estimate the standalone selling price of each performance obligation. Key assumptions to determine the standalone selling price may include forecasted revenues, development timelines, reimbursement rates for personnel costs, discount rates and probabilities of technical and regulatory success. Whenever we determine that a contract should be accounted for as a combined performance obligation over time, we determine the period over which the performance obligations will be performed and revenue will be recognized. Revenue is recognized using a cost-to-cost input model. Direct labor hours or full-time equivalents are typically used as the measure of performance. Significant management judgment is required in determining the level of effort required under an arrangement and the period over which we are expected to complete our performance obligations under an arrangement. We evaluate our collaborative agreements for proper classification in our consolidated statements of comprehensive loss based on the nature of the underlying activity. Transactions between collaborators recorded in our consolidated statements of comprehensive loss are recorded on either a gross or net basis, depending on the characteristics of the collaborative relationship. We generally reflect amounts due under our collaborative agreements related to cost-sharing of development activities as revenue if we have a vendor-customer relationship with our collaborator. Costs incurred or shared with our collaboration partners that are deemed to be joint-risk sharing activities are recorded as an adjustment to the related operating expense captions. For revenue generating arrangements where we, as a vendor, provide consideration to a licensor or collaborator, as a customer, we apply the accounting standard that governs such transactions. This standard addresses the accounting for revenue arrangements where both the vendor and the customer make cash payments to each other for services and/or products. A payment to a customer is presumed to be a reduction of the transaction price unless we receive an identifiable benefit for the payment and we can reasonably estimate the fair value of the benefit received. Payments to a customer that are deemed a reduction of the transaction price are recorded first as a reduction of revenue, to the extent of both cumulative revenue recorded to date and probable future revenues, which include any unamortized deferred revenue balances, under all arrangements with such customer, and then as an expense. Payments that are not deemed to be a reduction of the transaction price are recorded as an expense. Consideration that does not meet the requirements to satisfy the above revenue recognition criteria is recorded as deferred revenue in the accompanying consolidated balance sheets. Although we follow detailed guidelines in measuring revenue, certain judgments affect the application of our revenue policy. For example, in connection with our existing collaboration agreements, we have recorded on our consolidated balance sheets short-term and long-term deferred revenue based on our best estimate of when such revenue will be recognized. Short-term deferred revenue consists of amounts that are expected to be recognized as revenue in the next 12 months. Amounts that we expect will not be recognized within the next 12 months are classified as long-term deferred revenue. However, this estimate is based on our current operating plan and, if our operating plan should change in the future, we may recognize a different amount of deferred revenue over the next 12-month period. The estimate of deferred revenue also reflects management’s estimate of the periods of our involvement in certain of our collaborations. Our performance obligations under these collaborations consist of participation on steering committees and the performance of other research and development services. In certain instances, the timing of satisfying these obligations can be difficult to estimate. Accordingly, our estimates may change in the future. Such changes to estimates would result in a change in revenue recognition amounts. If these estimates and judgments change over the course of these agreements, it may affect the timing and amount of revenue that we recognize and record in future periods. At December 31, 2018, we had short-term and long-term deferred revenue of $3.5 million and $0.5 million, respectively, all of which was related to our collaboration with Vir. Cost of Goods Sold Cost of goods sold includes the cost of producing and distributing inventories that are related to product revenues during the respective period (including salary-related and stock-based compensation expenses for employees involved with production and distribution, freight and indirect overhead costs), third-party royalties payable on our net product revenues and amortization of intangible assets associated with ONPATTRO. Cost of goods sold may also include costs related to excess or obsolete inventory adjustment charges, abnormal costs, unabsorbed manufacturing and overhead costs, and manufacturing variances. Other Income As described more fully below in Note 9, Dicerna Pharmaceuticals, Inc., or During the fourth quarter of 2018, in connection with the completion of certain business development activities by Dicerna, the $13.0 million cash payment, included in prepaid expenses and other current assets on our consolidated balance sheet, became due and we accreted the remaining discount and recorded $4.0 million in interest income on our consolidated statements of comprehensive loss. Income Taxes We use the asset and liability method of accounting for income taxes. Under the asset and liability method, deferred tax assets and liabilities reflect the impact of temporary differences between amounts of assets and liabilities for financial reporting purposes and such amounts as measured under enacted tax laws. A valuation allowance is required to offset any net deferred tax assets if, based upon the available evidence, it is more likely than not that some or all of the deferred tax asset will not be realized. Accounting for income taxes requires a two-step approach to recognize and measure uncertain tax positions. The first step is to evaluate the tax position for recognition by determining if, based on the technical merits, it is more likely than not that the position will be sustained upon audit, including resolution of related appeals or litigation processes, if any. The second step is to measure the tax benefit as the largest amount that is more than 50 percent likely of being realized upon ultimate settlement. We re-evaluate these uncertain tax positions on a quarterly basis. This evaluation is based on factors including, but not limited to, changes in facts or circumstances, changes in tax law, effectively settled issues under audit and new audit activity. Any change in these factors could result in the recognition of a tax benefit or an additional charge to the tax provision. As of December 31, 2018, we have recorded no interest and penalty expense related to uncertain tax positions. Research and Development Expenses We record research and development expenses as incurred. Included in research and development expenses are wages, stock-based compensation expenses, benefits and other operating costs, facilities, supplies, external services, clinical trial and manufacturing costs, costs related to our collaboration arrangements and overhead directly related to our research and development operations, as well as costs to acquire technology licenses. We have entered into several license agreements for rights to utilize certain technologies. The terms of the licenses may provide for upfront payments, annual maintenance payments, milestone payments based upon certain specified events being achieved and royalties on product sales. We charge costs to acquire and maintain licensed technology that has not reached technological feasibility and does not have alternative future use to research and development expense as incurred. During the years ended December 31, 2018, 2017 and 2016, we charged to research and development expense costs associated with license fees of $8.0 million, $7.7 million and $2.4 million, respectively. Stock-Based Compensation We have stock incentive plans and an employee stock purchase plan under which we grant equity instruments. We may also grant inducement stock grants outside of our stock incentive plans. We account for all stock-based awards granted to employees at their fair value and generally recognize compensation expense over the vesting period of the award. Determining the amount of stock-based compensation to be recorded requires us to develop estimates of fair values of stock options as of the grant date. We calculate the grant date fair values of stock options using the Black-Scholes valuation model. Our expected stock price volatility assumption is based on the historical volatility of our publicly traded stock. The fair value of restricted stock awards granted to employees is based upon the quoted closing market price per share on the date of grant. Expense for time-based restricted stock awards is recognized over the vesting period. For performance-based stock option and restricted stock awards, we begin to recognize expense when we determine that the achievement of such performance conditions is deemed probable. This determination requires significant judgment by management. At the probable date, we record a cumulative

PRODUCT REVENUES, NET

PRODUCT REVENUES, NET	12 Months Ended
	Dec. 31, 2018
Revenue From Contract With Customer [Abstract]
PRODUCT REVENUES, NET	3. PRODUCT REVENUES, NET During the year ended December 31, 2018, we recorded product revenues, net of $12.5 million, which consisted of commercial sales of ONPATTRO in the U.S. and several countries in Europe. The following table summarizes balances and activity in each product revenue allowance and reserve category during the year ended December 31, 2018, in thousands, related to sales of ONPATTRO subsequent to its approval by the FDA and EC in August 2018: Chargebacks Rebates Trade Discounts and Allowances Returns Reserve Other Incentives Total Beginning balance $ — $ — $ — $ — $ — $ — Provision related to current period sales 1,553 2,528 292 106 551 5,030 Credit or payments made during the period (640 ) — (74 ) — (336 ) (1,050 ) Total $ 913 $ 2,528 $ 218 $ 106 $ 215 $ 3,980

SIGNIFICANT AGREEMENTS

SIGNIFICANT AGREEMENTS	12 Months Ended
	Dec. 31, 2018
Organization Consolidation And Presentation Of Financial Statements [Abstract]
SIGNIFICANT AGREEMENTS	4 . SIGNIFICANT AGREEMENTS The following table summarizes our total consolidated net revenues from collaborators, for the periods indicated, in thousands: Year Ended December 31, Description 2018 2017 2016 Sanofi Genzyme $ 46,000 $ 54,625 $ 32,015 Vir Biotechnology 12,778 1,464 — MDCO 2,789 30,217 11,220 Other 806 3,606 3,924 Total net revenues from collaborators $ 62,373 $ 89,912 $ 47,159 The following table summarizes our total consolidated net revenues from collaborators, using the prior revenue standard, for the periods indicated, in thousands: Year Ended December 31, Description 2018 2017 2016 Sanofi Genzyme $ 91,738 $ 54,625 $ 32,015 Vir Biotechnology 12,778 1,464 — MDCO 7,184 30,217 11,220 Other 806 3,606 3,924 Total net revenues from collaborators $ 112,506 $ 89,912 $ 47,159 The following table presents the balance of our contract liabilities related to our collaboration agreements at December 31, 2018 and January 1, 2018, in thousands: At December 31, 2018 At January 1, 2018 Contract liabilities: Deferred revenues $ 3,954 $ 16,570 During the year ended December 31, 2018, we recognized the following revenues as a result of the change in the contract liability balances related to our collaboration agreements, in thousands: Revenue recognized in the period from: Year Ended December 31, 2018 Amounts included in contract liability at the beginning of the period $ 16,570 The following table provides the research and development expenses incurred by type that are directly attributable to our collaboration agreements by collaboration partner for the periods indicated, in thousands: Year Ended December 31, 2018 2017 2016 Sanofi Genzyme Vir MDCO Ionis Sanofi Genzyme Vir MDCO Ionis Sanofi Genzyme Vir MDCO Ionis Research and development Clinical trial and manufacturing $ 36,600 $ 7,272 $ 1,664 $ — $ 174,901 $ 1,134 $ 5,421 $ — $ 150,179 $ — $ 1,211 $ — External services 5,340 8,251 2 2,150 4,475 926 — 3,250 7,366 — — — Other 1,279 548 203 1,097 5,327 — 106 — 3,035 — 64 525 Total research and development expenses $ 43,219 $ 16,071 $ 1,869 $ 3,247 $ 184,703 $ 2,060 $ 5,527 $ 3,250 $ 160,580 $ — $ 1,275 $ 525 The research and development expenses incurred for each agreement listed in the table above consist of costs incurred for external development and manufacturing services for which we are reimbursed, licensing payments made to the counterparty to such agreement and costs directly attributable to Sanofi Genzyme transition services. In addition, these expenses include a reasonable estimate of compensation and related costs as billed to our counterparties. As part of our revenue recognition policy adopted January 1, 2018, the costs in the above table are considered an input in our determination of transaction price when they relate to consideration received for the delivery of goods or services. For the years ended December 31, 2018, 2017 and 2016, we did not incur material selling, general and administrative expenses related to our significant agreements. Product Alliances Sanofi Genzyme Collaboration In January 2014, we entered into a global, strategic collaboration with Sanofi Genzyme to discover, develop and commercialize RNAi therapeutics as Genetic Medicines to treat orphan diseases, referred to as the 2014 Sanofi Genzyme collaboration. The 2014 Sanofi Genzyme collaboration superseded and replaced the previous collaboration between us and Sanofi Genzyme entered into in October 2012 to develop and commercialize RNAi therapeutics targeting TTR for the treatment of hereditary ATTR amyloidosis, including patisiran and revusiran, in Japan and the Asia-Pacific region. On January 6, 2018, we and Sanofi Genzyme entered into an amendment to our 2014 Sanofi Genzyme collaboration. In connection and simultaneously with entering into the amendment to the 2014 Sanofi Genzyme collaboration, we and Sanofi Genzyme also entered into the Exclusive TTR License and the AT3 License Terms. As a result, we have the exclusive right to pursue the further global development and commercialization of all TTR products, including ONPATTRO, vutrisiran and any back-up products, and Sanofi Genzyme has the exclusive right to pursue the further global development and commercialization of fitusiran and any back-up products. The January 2018 transaction was subject to customary closing conditions and clearances, including clearance under the Hart-Scott-Rodino Antitrust Improvements Act, and closed during the first quarter of 2018. 2012 Sanofi Genzyme Agreement Under the 2012 Sanofi Genzyme agreement, Sanofi Genzyme paid us an upfront cash payment of $22.5 million. We were also entitled to receive certain milestone payments under the 2012 Sanofi Genzyme agreement. In the fourth quarter of 2013, we earned $11.0 million in patisiran development milestones under the 2012 Sanofi Genzyme agreement. We determined that the deliverables under the 2012 Sanofi Genzyme agreement included the license, a joint steering committee and any additional TTR-specific RNAi therapeutic compounds that comprised the TTR program. We also determined that, pursuant to the accounting guidance governing revenue recognition on multiple element arrangements, the license and undelivered joint steering committee and any additional TTR-specific RNAi therapeutic compounds did not have standalone value due to the specialized nature of the services to be provided by us. In addition, while Sanofi Genzyme had the ability to grant sublicenses, it could not sublicense all or substantially all of its rights under the 2012 Sanofi Genzyme agreement. The uniqueness of our services and the limited sublicense right were indicators that standalone value was not present in the arrangement. Therefore, the deliverables were not separable and, accordingly, the license and undelivered services were treated as a single unit of accounting. We were unable to reasonably estimate the period of performance under the 2012 Sanofi Genzyme agreement, as we were unable to estimate the timeline of our deliverables related to the deliverable for any additional TTR-specific RNAi therapeutic compounds. Through December 31, 2013, under the prior revenue standard, we had deferred all revenue, or $33.5 million, under the 2012 Sanofi Genzyme agreement. 2014 Sanofi Genzyme Collaboration, as amended in January 2018 In January 2014, we entered into the 2014 Sanofi Genzyme collaboration. As noted above, the 2014 Sanofi Genzyme collaboration superseded and replaced the 2012 Sanofi Genzyme agreement and was amended in January 2018, at which time we also entered into the Exclusive TTR License and the AT3 License Terms. The 2014 Sanofi Genzyme collaboration is structured as an exclusive relationship for the worldwide development and commercialization of RNAi therapeutics in the field of Genetic Medicines, which includes our current and future Genetic Medicine programs that reach Human Proof-of-Principle Study Completion (as defined in the Sanofi Genzyme master agreement), or Human POP, by the end of 2019, subject to extension to the end of 2021 in various circumstances. We will retain product rights in the U.S., Canada and Western Europe, referred to as the Alnylam Territory, while Sanofi Genzyme will obtain exclusive rights to develop and commercialize collaboration products in the rest of the world, referred to as the Sanofi Genzyme Territory, together with worldwide rights for one product. Sanofi Genzyme’s rights under the 2014 Sanofi Genzyme collaboration, described in detail below, are structured as an opt-in that is triggered upon achievement of Human POP. We maintain development control for all programs prior to Sanofi Genzyme’s opt-in and maintain development and commercialization control after Sanofi Genzyme’s opt-in for all programs in the Alnylam Territory. We will retain global rights to any RNAi therapeutic Genetic Medicine program that does not reach Human POP by the end of 2019, subject to certain limited exceptions. We retain full rights to all current and future RNAi therapeutic programs outside of the field of Genetic Medicines, including the right to form new collaborations. Under the 2014 Sanofi Genzyme collaboration, Sanofi Genzyme’s specific license rights and the programs which Sanofi Genzyme opted into prior to the 2018 amendment include the following: • Regional license terms and programs — Upon opt-in, we will retain product rights in the Alnylam Territory, while Sanofi Genzyme will obtain exclusive rights to develop and commercialize the product in the Sanofi Genzyme Territory. Sanofi Genzyme can elect this license for any of our current and future Genetic Medicine programs that complete Human POP by the end of 2019, subject to limited extension. Development costs for products once Sanofi Genzyme exercises an option will be shared between Sanofi Genzyme and us, with Sanofi Genzyme responsible for twenty percent of the global development costs. Sanofi Genzyme will be required to make payments totaling up to $75.0 million per regional product, consisting of up to $55.0 million in development milestones and $20.0 million in commercial milestones. Sanofi Genzyme will also be required to pay tiered double-digit royalties up to twenty percent for each regional product based on annual net sales, if any, of such regional product by Sanofi Genzyme, its affiliates and sublicensees. Upon the effective date of the 2014 Sanofi Genzyme collaboration, Sanofi Genzyme expanded the scope of its regional license and collaboration for patisiran, which was originally established under the 2012 Sanofi Genzyme agreement. In September 2015, Sanofi Genzyme elected to opt into our fitusiran clinical development program for the treatment of hemophilia and other rare bleeding disorders under the regional license terms. Cost-sharing for the fitusiran program began in January 2016 under the regional license terms. Sanofi Genzyme also had the right to elect to co-develop and co-commercialize fitusiran in the Alnylam Territory pursuant to the co-development/co-commercialize license terms described below. In November 2016, Sanofi Genzyme exercised that right and elected to co-develop and co-commercialize fitusiran in the Alnylam Territory. In addition, during 2016, Sanofi Genzyme elected not to opt into the development and commercialization of givosiran or cemdisiran in the Sanofi Genzyme Territory. Sanofi Genzyme’s rights with respect to patisiran and fitusiran were modified in connection with the 2018 amendment, the Exclusive TTR License the AT3 License Terms, as described below. Sanofi • Co-development/co-commercialize license terms and programs — Upon opt-in, we retained product rights in the Alnylam Territory, while Sanofi Genzyme obtained exclusive rights to develop and commercialize the product in the Sanofi Genzyme Territory, and to co-commercialize the product in the Alnylam Territory. Upon the effective date of the 2014 Sanofi Genzyme collaboration, Sanofi Genzyme expanded its regional rights for revusiran, which were originally granted under the 2012 Sanofi Genzyme agreement, to include a co-development/co-commercialize license and collaboration. In October 2016, we decided to discontinue development of revusiran. In our TTR program, we are also developing vutrisiran. Sanofi Genzyme had a right to elect a co-development/co-commercialize license for vutrisiran. As noted above, in November 2016, Sanofi Genzyme exercised its right to elect a co-development/co-commercialize license for fitusiran. Development costs for co-development/co-commercialize products, once Sanofi Genzyme exercised an option, were shared between Sanofi Genzyme and us, with Sanofi Genzyme responsible for fifty percent of the global development costs. In connection with the exercise of its co-development/co-commercialize rights for fitusiran, Sanofi Genzyme paid us approximately $6.0 million in January 2017 for its incremental share of co-development costs incurred from January 2016 through September 2016. Sanofi Genzyme was required to make certain milestone payments for fitusiran, and, prior to the discontinuation of the revusiran program, was required to make certain milestone payments for revusiran. In December 2014, we earned a development milestone payment of $25.0 million based upon the initiation of the first global Phase 3 clinical trial for revusiran. Sanofi Genzyme was also obligated to pay us a milestone of $25.0 million upon the dosing of the first patient in our ATLAS Phase 3 program for fitusiran. In addition, Sanofi Genzyme was required to pay tiered double-digit royalties up to twenty percent for each co-development/co-commercialize product based on annual net sales, if any, in the Sanofi Genzyme Territory for such co-development/co-commercialize product by Sanofi Genzyme, its affiliates and sublicensees. The parties were to share profits equally and we expected to book product sales in the Alnylam Territory. In connection with the 2018 amendment, the Exclusive TTR License the AT3 License Terms, as described below • Global license terms and programs — Sanofi Genzyme continues to have one right to a global license through 2019, subject to limited extension, for a future Genetic Medicine program that was not one of our defined Genetic Medicine programs as of the effective date of the 2014 Sanofi Genzyme collaboration. Upon opt-in, Sanofi Genzyme will obtain a worldwide license to develop and commercialize the product. Sanofi Genzyme Exclusive TTR License and AT3 License Terms As noted above, the 2018 amendment, together with the Exclusive TTR License and the AT3 License Terms, revise the terms and conditions of the 2014 Sanofi Genzyme collaboration to (i) provide us the exclusive right to pursue the further global development and commercialization of all TTR products, including ONPATTRO, vutrisiran and any back-up products, (ii) provide Sanofi Genzyme the exclusive right to pursue the further global development and commercialization of fitusiran and any back-up products and (iii) terminate the previous co-development and co-commercialization rights related to revusiran, vutrisiran and fitusiran under the 2014 Sanofi Genzyme collaboration. Going forward, we are funding all development and commercialization costs for ONPATTRO and vutrisiran. We also funded development and commercialization costs for fitusiran through the transition period, up to a cap of $50.0 million, after which Sanofi Genzyme became responsible for funding all development and commercialization costs for fitusiran. We completed the transition period relating to the transition of the fitusiran program to Sanofi Genzyme in 2018. Each party was responsible for its costs associated with the transfer of the respective program to the other party. Under the 2018 amendment and the Exclusive TTR License, Sanofi Genzyme will be eligible to receive (i) royalties up to twenty-five percent, increasing over time, based on annual net sales of ONPATTRO in territories excluding the U.S., Canada and Western Europe, provided royalties on annual net sales of ONPATTRO in Japan will be twenty-five percent beginning as of the effective date of the Exclusive TTR License, (ii) tiered royalties of fifteen to thirty percent based on global annual net sales of vutrisiran (consistent with the royalties due to us from Sanofi Genzyme on fitusiran), and (iii) tiered royalties of up to fifteen percent based on global annual net sales of any back-up products, in each case by us, our affiliates and our sublicensees. Except as described below, there will be no additional milestones due to either party with respect to ONPATTRO, vutrisiran or fitusiran. In consideration for the rights granted to Sanofi Genzyme under the 2018 amendment and the AT3 License Terms, Sanofi Genzyme was required to make one milestone payment of $50.0 million following the dosing of the first patient in the ATLAS Phase 3 program for fitusiran. This milestone was achieved in the first quarter of 2018. In addition, we will be eligible to receive tiered royalties of fifteen to thirty percent based on global annual net sales of fitusiran and up to fifteen percent based on global annual net sales of any back-up products, in each case by Sanofi Genzyme, its affiliates and its sublicensees. We intend to continue to work with Sanofi Genzyme to ensure continuity for the supply of fitusiran for ongoing clinical studies, and, at Sanofi Genzyme’s request, commercial sales. Sanofi Genzyme also has the right to manufacture fitusiran. Due to the uncertainty of pharmaceutical development and the high historical failure rates generally associated with drug development, we may not receive any additional milestone payments or any royalty payments from Sanofi Genzyme under the 2014 Sanofi Genzyme collaboration, as amended, or any royalty payments under the AT3 License Terms. The 2014 Sanofi Genzyme collaboration, as amended, will continue to be governed by an alliance joint steering committee that is comprised of an equal number of representatives from each party. Additional committees manage various aspects of each regional and global program and oversee certain matters that may arise under the Exclusive TTR License and the AT3 License Terms. The original master agreement (including the license terms appended thereto), as well as the Exclusive TTR License and the AT3 License Terms, contain certain termination provisions, including for material breach by the other party. In addition, we have the right to terminate Exclusive TTR License without cause with respect to any or all licensed products at any time upon six months’ prior written notice and Sanofi Genzyme has the right to terminate the AT3 License Terms without cause with respect to any particular licensed product at any time upon six months’ prior written notice. Unless terminated earlier pursuant to its terms, the master agreement will terminate upon the last to expire of any of the option periods under the master agreement or the license terms appended thereto. The term of the Exclusive TTR License expires on a licensed product-by-licensed product and country-by-country basis upon expiration of the last royalty term to expire under the agreement, where a royalty term is defined as the latest to occur of (a) expiration of the last valid claim of patent rights covering a licensed product; (b) the expiration of Regulatory Exclusivity for a licensed product, as defined in the Exclusive TTR License; or (c) the twelfth anniversary of the first commercial sale of the licensed product in such country. The term of the AT3 License Terms expires on a licensed product-by-licensed product and country-by-country basis upon expiration of the last royalty term to expire under the agreement, where a royalty term is defined as the latest to occur of (x) the expiration of the last valid claim of patent rights covering a licensed product; (y) the expiration of Regulatory Exclusivity for a licensed product, as defined in the AT3 License Terms; or (z) the twelfth anniversary of the first commercial sale of the licensed product in such country. As noted above, the Sanofi Genzyme collaboration originally entered into in 2012 was materially modified during its term when the agreement was amended in 2014, prior to our adoption of the new revenue standard on January 1, 2018. In accordance with the new revenue standard, we evaluated the Sanofi Genzyme collaboration with the aggregate effect of all modifications when identifying performance obligations, determining the transaction price and allocating the transaction price. We determined that certain promises included in these agreements are within the scope of the new revenue standard since Sanofi Genzyme is a customer with respect to the license of the rights to its territories. We also determined, however, that certain aspects of these agreements are within the scope of the collaboration accounting guidance with respect to co-commercialization activities as these activities are joint risk-sharing and are not reflective of a vendor-customer relationship. We apply the new revenue standard to all promises associated with the transfer of goods and services to a customer. We concluded that Sanofi Genzyme meets the definition of a customer as we were delivering intellectual property and know-how rights as well as research and development activities for the TTR programs and fitusiran programs in support of territories in which we are not jointly sharing the risks and rewards. We concluded that the accounting for the original 2014 Sanofi Genzyme collaboration, and the collaboration, as amended, should be assessed as separate contracts for (i) the patisiran and revusiran (TTR) programs, upon the initiation of the 2014 Sanofi Genzyme collaboration, and (ii) the subsequent opt-in by Sanofi Genzyme for the fitusiran program. In addition, we determined that the Sanofi Genzyme collaboration met the requirements to be accounted for as a contract, including that it is probable that we will collect the consideration to which we are entitled in exchange for the goods or services that will be delivered to Sanofi Genzyme. We identified contract promises or deliverables for licenses to our intellectual property and know-how rights, associated development activities, joint steering committee participation and information exchange. We determined that, pursuant to the new revenue standard (and consistent with our accounting prior to the adoption of the new revenue standard), the performance obligations were not separately identifiable and were not distinct (and did not have standalone value) due to the specialized nature of the services to be provided by us and the dependent relationship between the performance obligations. Given this fact pattern, we concluded each of the TTR and fitusiran contracts have a single identified or combined performance obligation. When applying the previous revenue standard, we determined that the co-commercialization activities prior to the 2018 amendment were within the scope of the collaboration accounting standard since both parties would actively participate in the co-commercialization and be subject to significant risks and rewards. As a result of this determination, we recorded any payments or cash receipts for these joint risk-sharing activities as an adjustment to the related operations expense captions. The amounts recorded as a reduction of our selling, general and administrative activities were not material. The transaction price as of January 1, 2018 of $127.6 million for the 2014 Sanofi Genzyme collaboration related to the license to the TTR programs included the $22.5 million upfront payment and $11.0 million of development milestone payments earned under the now superseded 2012 Sanofi Genzyme agreement, a $25.0 million development milestone payment for revusiran achieved in 2014, the estimated patisiran and revusiran cost-share reimbursements, net of payments to Sanofi Genzyme, of $63.6 million and $57.0 million, respectively, and the $51.5 million equity discount related to the stock purchase agreement, described below. Since the fair value of the stock at the time of closing was more than the consideration received by us by $51.5 million, we reduced the transaction price of the license and collaboration contract, treating the equity discount in a manner consistent with a payment to the customer. The transaction price related to our license to the fitusiran program as of January 1, 2018, accounted for as a separate agreement, included estimated fitusiran development cost-share reimbursements of $147.3 million, net of payments to Sanofi Genzyme. There are no refund provisions in the agreement and, therefore, none of the consideration received to date has been excluded from the transaction price calculation. None We allocated the transaction price to the combined performance obligation. We have determined that this combined performance obligation is satisfied over time based on our performance that is creating or enhancing an asset that Sanofi Genzyme controls. In this instance, Sanofi Genzyme received control over the asset, or the licensed intellectual property, and know-how, at the time the contract was executed since the licensed intellectual property and know-how meet the definition of functional intellectual property per the new revenue standard, which defines functional intellectual property as intellectual property that derives a substantial portion of its utility from its standalone functionality rather than the entity’s ongoing activities (thus, once the asset is fully developed, our ongoing involvement is not required for the licensee to derive value). The other promises included in the performance obligation, however, are enhancing the controlled asset, and thus the combined performance obligation is being satisfied over time. The new revenue standard requires a single method of measuring performance for each performance obligation satisfied over time. Since we do not have a reliable method of estimating progress based upon its outputs, it was determined that the most reliable method of estimating progress would be using a cost-to-cost input method. We have determined that our completion of certain clinical and regulatory development tasks is relevant and directly related to our progress in completing the combined performance obligation. As such, we measured our progress upon adoption and will continue to measure our progress during each reporting period based upon the amount of development costs incurred divided by the total amount of development costs expected to be incurred over the course of the agreement. We exclude costs that are not related to our completion of this performance obligation, such as the completion of tasks (and incurring of costs) associated with the marketing and commercialization of the drug. We estimated our internal costs during the last three years, excluding non-reimbursable costs that were not deemed to directly relate to the delivery of the development services to Sanofi Genzyme. Historically, we have been unable to reliably measure our performance based upon our lack of historical experience in completing the development of a drug candidate and have, as a result, defaulted to straight-line attribution for many of our licensing agreements. At the time of adoption of the new revenue standard, however, we have completed a substantial portion of our development obligations and determined we have sufficient information to estimate the remaining development costs for the fitusiran program and sufficient experience to reasonably estimate our development costs. We determined that the 2018 amendment, together with the Exclusive TTR License and the AT3 License Terms, referred to as the 2018 restructured agreement, are included in the scope of the modification provisions of the new revenue standard. We had identified that the agreement for the TTR programs under the 2014 Sanofi Genzyme collaboration should be accounted for separately from any subsequent option exercises, including with respect to fitusiran. Therefore, we concluded it is appropriate to account for the 2018 restructured agreement as two separate modifications to the 2014 Sanofi Genzyme collaboration: one related to the TTR programs and one related to the fitusiran program. Our conclusions related to scoping under the prior revenue standard are consistent with the new revenue standard. As noted above, the 2018 amendment, together with the Exclusive TTR License, provide us with the exclusive right to pursue the further global development and commercialization of all TTR products, including ONPATTRO. We are responsible for all development and commercialization costs for ONPATTRO and vutrisiran . As of the 2018 restructured agreement, we are no longer required to complete the delivery of any of the performance obligations under the agreement related to the TTR programs. As a result, the transaction price prior to the 2018 amendment has been reduced as we are no longer entitled to cost-share reimbursements or any of the previously constrained consideration, such as milestones and royalties. Since the 2018 amendment affected the transaction price but did not add any incremental and distinct performance obligations, we concluded this amendment should be accounted for as a change to the existing agreement and recorded the revenue on a cumulative catch-up basis. At the time of the 2018 amendment, we had $2.9 million in revenue deferred as a contract liability on our consolidated balance sheet related to this contract for TTR programs, all of which we recognized in the first quarter of 2018 under a cost-to-cost input model as we no longer expected to incur costs associated with the delivery of goods or services. If we had not adopted the new revenue standard, at the time of the 2018 restructured agreement, we would have had $25.8 million of deferred revenues on our consolidated balance sheet that would have been recognized in full upon the date of the 2018 restructured agreement as we would have similarly concluded there were no ongoing deliverables under the 2018 restructured agreement related to the TTR programs. We expect to record future royalties payable to Sanofi Genzyme with respect to any sales of ONPATTRO within cost of goods sold on our consolidated statements of comprehensive loss as Sanofi Genzyme is no longer considered our customer after the 2018 restructured agreement for sales of all TTR products, including ONPATTRO, and as such, these royalty payments are outside of the scope of the new revenue standard, including with respect to principal versus agent guidance. The 2018 amendment, together with the AT3 License Terms, as noted above, provide Sanofi Genzyme the exclusive right to pursue the further global development and commercialization of fitusiran and any back-up products and terminates the previous co-development and co-commercialization rights related to fitusiran under the 2014 Sanofi Genzyme collaboration. The 2018 restructured agreement provides a broader license that permits global development, manufacturing and commercialization, and we were required to facilitate the transfer of all ongoing activities, contracts, intellectual property, know-how and other materials and information related to fitusiran to Sanofi Genzyme. In connection with the 2018 restructured agreement for fitusiran, we funded development and commercialization costs for fitusiran through the transition period, which was completed in 2018, up to a limit of $50.0 million. The only milestone under the 2018 restructured agreement, which was achieved in the first quarter of 2018 , was considered variable consideration for the license and transition services related to the fitusiran program. We agreed to reimburse Sanofi Genzyme for certain transition activities that are reflected as a reduction in the transaction price. As a result, the transaction price has been reduced as we are no longer entitled to cost-share reimbursements or any of the previously constrained consideration, such as milestones and royalties. We concluded that the modification that resulted from the 2018 restructured agreement related to fitusiran would be treated as a termination and replacement of the 2014 Sanofi Genzyme collaboration and accounted for prospectively as the remaining license and transition services are considered distinct from that under the agreement prior to this modification. However, the incremental consideration under the 2018 restructured agreement does not directly reflect the standalone selling price of the incremental performance obligation. Therefore, we concluded the 2018 restructured agreement for fitusiran should be accounted for on a prospective basis. At the time of the 2018 amendment, we had $0.6 million in revenue deferred as a contract liability on our consolidated balance sheet related to the 2014 Sanofi Genzyme collaboration for the fitusiran program. The transaction price of the 2018 restructured agreement for fitusiran is $37.6 million, primarily related to the $50.0 million milestone that was achieved in the first quarter of 2018, . Consistent with our accounting prior to this 2018 modification, we are applying the sales-based royalty under the new revenue standard to exclude from the transaction price the royalties earned on Sanofi Genzyme’s sales of fitusiran as we have determined in the context of all the performance obligations, including those delivered prior to the 2018 modification, that the value of the broader license will continue to represent a substantial portion of the value provided to Sanofi Genzyme; and therefore the license to the intellectual property is the predomi

INVENTORY

INVENTORY	12 Months Ended
	Dec. 31, 2018
Inventory Disclosure [Abstract]
INVENTORY	5. INVENTORY The following table presents our inventory of ONPATTRO at December 31, 2018 and 2017, in thousands: At December 31, 2018 2017 Raw materials $ 8,709 $ — Work in process 15,262 — Finished goods 97 — Total inventory $ 24,068 $ — At December 31, 2018, all of our inventory was related to ONPATTRO, which was approved by the FDA and the EC in August 2018. In the third quarter of 2018, we began to capitalize inventory costs for ONPATTRO as a result of the approval of ONPATTRO by the FDA and commercial sales forecasts for ONPATTRO. Prior to the third quarter of 2018, we recorded the costs associated with manufacturing ONPATTRO as research and development expenses on our consolidated statements of comprehensive loss. At December 31, 2018, we determined a reserve related to ONPATTRO inventory is not required based on our evaluation of factors including commercial sales forecasts for ONPATTRO and the shelf life of ONPATTRO inventory.

FAIR VALUE MEASUREMENTS

FAIR VALUE MEASUREMENTS	12 Months Ended
	Dec. 31, 2018
Fair Value Disclosures [Abstract]
FAIR VALUE MEASUREMENTS	6 . FAIR VALUE MEASUREMENTS The following tables present information about our assets that are measured at fair value on a recurring basis at December 31, 2018 and 2017, and indicate the fair value hierarchy of the valuation techniques we utilized to determine such fair value, in thousands: Description At December 31, 2018 Quoted Prices in Active Markets (Level 1) Significant Observable Inputs (Level 2) Significant Unobservable Inputs (Level 3) Cash equivalents: U.S. treasury securities $ 221,281 $ — $ 221,281 $ — Money market funds 102,445 102,445 — — Marketable debt securities: — Certificates of deposit 8,951 — 8,951 — Commercial paper 57,197 — 57,197 — Corporate notes 232,410 — 232,410 — U.S. government-sponsored enterprise securities 39,018 — 39,018 — U.S. treasury securities 325,227 — 325,227 — Marketable equity securities 1,206 1,206 — Restricted cash (money market funds) 1,477 1,477 — — Total $ 989,212 $ 105,128 $ 884,084 $ — Description At December 31, 2017 Quoted Prices in Active Markets (Level 1) Significant Observable Inputs (Level 2) Significant Unobservable Inputs (Level 3) Cash equivalents: Commercial paper $ 82,262 $ — $ 82,262 $ — Corporate notes 18,116 — 18,116 — U.S. government-sponsored enterprise securities 231,122 — 231,122 — U.S. treasury securities 62,855 — 62,855 — Money market funds 122,986 122,986 — — Marketable debt securities: — Certificates of deposit 30,200 — 30,200 — Commercial paper 56,951 — 56,951 — Corporate notes 373,252 — 373,252 — U.S. government-sponsored enterprise securities 398,298 — 398,298 — U.S. treasury securities 200,475 — 200,475 — Restricted cash (money market funds) 1,471 1,471 — — Total $ 1,577,988 $ 124,457 $ 1,453,531 $ — For the years ended The fair value of our long-term debt at December 31, 2018, computed pursuant to a discounted cash flow technique using a market interest rate, was $30.1 million and is considered a Level 3 fair value measurement. The effective interest rate reflects the current market rate.

MARKETABLE DEBT SECURITIES

MARKETABLE DEBT SECURITIES	12 Months Ended
	Dec. 31, 2018
Investments Debt And Equity Securities [Abstract]
MARKETABLE DEBT SECURITIES	7 . MARKETABLE DEBT SECURITIES We obtain fair value measurement data for our marketable debt securities from independent pricing services. We perform validation procedures to ensure the reasonableness of this data. This includes meeting with the independent pricing services to understand the methods and data sources used. Additionally, we perform our own review of prices received from the independent pricing services by comparing these prices to other sources and confirming those securities are trading in active markets. The following tables summarize our marketable debt securities at December 31, 2018 and 2017, in thousands: At December 31, 2018 Amortized Cost Gross Unrealized Gains Gross Unrealized Losses Fair Value Certificates of deposit $ 8,951 $ — $ — $ 8,951 Commercial paper 57,197 — — 57,197 Corporate notes 232,695 — (285 ) 232,410 U.S. government-sponsored enterprise securities 39,031 — (13 ) 39,018 U.S. treasury securities 325,350 1 (124 ) 325,227 Total $ 663,224 $ 1 $ (422 ) $ 662,803 At December 31, 2017 Amortized Cost Gross Unrealized Gains Gross Unrealized Losses Fair Value Certificates of deposit $ 30,200 $ — $ — $ 30,200 Commercial paper 56,951 — — 56,951 Corporate notes 373,736 11 (495 ) 373,252 U.S. government-sponsored enterprise securities 399,281 — (983 ) 398,298 U.S. treasury securities 200,649 1 (175 ) 200,475 Total $ 1,060,817 $ 12 $ (1,653 ) $ 1,059,176 We classify our debt security investments based on their contractual maturity dates. The following table summarizes our available-for-sale debt securities by contractual maturity, at December 31, 2018, in thousands: At December 31, 2018 Amortized Cost Fair Value Less than one year $ 663,224 $ 662,803 Greater than one year but less than five years — — Total $ 663,224 $ 662,803

PROPERTY, PLANT AND EQUIPMENT,

PROPERTY, PLANT AND EQUIPMENT, NET	12 Months Ended
	Dec. 31, 2018
Property Plant And Equipment [Abstract]
PROPERTY, PLANT AND EQUIPMENT, NET	8 . PROPERTY, PLANT AND EQUIPMENT, NET Property, plant and equipment, net consist of the following at December 31, 2018 and 2017, in thousands: At December 31, 2018 2017 Laboratory equipment $ 43,427 $ 40,462 Computer equipment and software 13,495 9,608 Furniture and fixtures 7,238 5,844 Leasehold improvements 65,928 50,612 Land 9,080 9,080 Construction in progress 260,975 133,645 400,143 249,251 Less: accumulated depreciation (79,485 ) (67,351 ) $ 320,658 $ 181,900 During the years ended December 31, 2018, 2017 and 2016, we recorded $12.8 million, $11.9 million and $9.6 million, respectively, of depreciation expense related to our property, plant and equipment. Manufacturing Facility In April 2016, we purchased 12 acres of undeveloped land in Norton, Massachusetts. We are constructing a manufacturing facility at this site for drug substance for clinical and commercial use. At December 31, 2018 and 2017, property, plant and equipment, net, on our consolidated balance sheets reflects $227.7 million and $140.5 million, respectively, of land and associated costs related to the construction of our drug substance manufacturing facility.

COMMITMENTS AND CONTINGENCIES

COMMITMENTS AND CONTINGENCIES	12 Months Ended
	Dec. 31, 2018
Commitments And Contingencies Disclosure [Abstract]
COMMITMENTS AND CONTINGENCIES	9 . COMMITMENTS AND CONTINGENCIES Technology License and Other Commitments We have licensed from third parties the rights to use certain technologies and information in our research processes as well as in ONPATTRO and any other products that we may develop. In accordance with the related license or technology agreements, we are required to make certain fixed payments to the counterparty over various agreement terms. Many of these agreement terms are consistent with the remaining lives of the underlying intellectual property that we have licensed. At December 31, 2018, we expect to make the following fixed and cancelable payments under existing license agreements, in thousands: Year Ending December 31, 2019 $ 1,453 2020 795 2021 745 2022 545 2023 525 Thereafter 525 Total $ 4,588 We in-license technology from a number of sources, including Ionis, Merck Sharp & Dohme Corp, or Merck, and Arbutus Biopharma Corporation Facility Leases 300 Third Street We lease office and laboratory space located at 300 Third Street, Cambridge, Massachusetts which to date has served as our corporate headquarters under a non-cancelable real property lease agreement by and between us and ARE-MA Region No. 28, LLC, or ARE-MA, dated as of September 26, 2003, as amended by five amendments, referred to collectively as the 300 Third Street Lease. Pursuant to the 300 Third Street Lease, we lease a total of approximately 129,000 square feet of office and laboratory space. The term of the 300 Third Street Lease was set to expire on September 30, 2021. On August 14, 2018, we and ARE-MA entered into a Sixth Amendment to Lease, or the Sixth Amendment, pursuant to which the term of the 300 Third Street Lease was extended for an additional twelve years and four months, through January 31, 2034. Under the Sixth Amendment, we have the option to extend the 300 Third Street Lease, as amended, for two additional five-year terms. Beginning in October 2021, annual rent under the 300 Third Street Lease, as amended by the Sixth Amendment, exclusive of operating expenses and real property taxes, will be $10.5 million for the first twelve months, with annual increases of 2.5 percent thereafter. Under the terms of the Sixth Amendment, ARE-MA will provide a tenant improvement allowance up to $8.4 million, which may be used to fund appropriate improvements to the premises. 665 Concord Avenue On February 10, 2012, we entered into a non-cancelable real property lease agreement, or the BMR-665 Concord Avenue Lease, with BMR-Fresh Pond Research Park LLC for our manufacturing facility for patisiran formulated bulk drug product. In August 2016, we amended the BMR-665 Concord Avenue Lease to extend the term. Under the BMR-665 Concord Avenue Lease, we lease approximately 15,000 square feet of office and laboratory space located at 665 Concord Avenue, Cambridge, Massachusetts. The term of the BMR-665 Concord Avenue Lease expires on August 31, 2022. Under the amended BMR-665 Concord Avenue Lease, we have the option to extend the term for one additional five-year period. 675 West Kendall Street In April 2015, we entered into a non-cancelable real property lease, or the BMR-675 West Kendall Lease, with BMR-675 West Kendall Street, LLC, or BMR, for laboratory and office space located at 675 West Kendall Street, Cambridge, Massachusetts. We intend to move our corporate headquarters and research facility to this location in 2019. Under the terms of the BMR-675 West Kendall Lease, we lease approximately 295,000 square feet of laboratory and office space. The term of the BMR-675 West Kendall Lease commenced on May 1, 2018 and monthly rent payments became due commencing on February 1, 2019 upon substantial completion of the building improvements, and continue for 15 years, with options to renew for two terms of five years each, subject to the terms of the BMR-675 West Kendall Lease. Annual rent under the BMR-675 West Kendall Lease, exclusive of operating expenses and real property taxes, is $19.8 million for the first year, with annual increases of 3 percent thereafter. Under the terms of the BMR-675 West Kendall Lease, BMR will contribute a total of $56.1 million toward the cost of base building and tenant improvements. As of December 31, 2018, in connection with base building and tenant improvements to date, we received $25.4 million and have $12.5 million due to us from BMR that is included in prepaid expenses and other current assets on our consolidated balance sheet. In addition, in connection with the May 1, 2018 commencement of the BMR-675 West Kendall Lease, we were required to provide a $14.8 million security deposit that is recorded as restricted investments on our consolidated balance sheet as of December 31, 2018. 101 Main Street In May 2015, we entered into a non-cancelable real property lease agreement with RREEF America REIT II CORP. PPP, or RREEF, for office space located on several floors at 101 Main Street, Cambridge, Massachusetts. This lease supplements the initial lease entered into in March 2015 between us and RREEF for office space on a separate floor at the 101 Main Street location. Under the terms of the 101 Main Street leases, we lease approximately 72,000 square feet of office space at the 101 Main Street location. The term of the initial 101 Main Street lease, that commenced in March 2015, was set to expire on March 31, 2019. On September 27, 2018, we and RREEF entered into a Second Amendment to Lease, pursuant to which the term of the initial 101 Main Street lease was extended for an additional five years, through March 31, 2024, with an option to renew for one five-year term. The term of the additional 101 Main Street lease commenced in January 2016, and continues for five and a half years, with an option to renew for one five-year term. Initial annual rent for the initial lease and the additional lease, exclusive of operating expenses and real property taxes, was $1.7 million and $3.5 million, respectively, with annual increases of $1/square foot under each lease thereafter. Rent payments commenced in May 2015 under the initial lease and rent payments commenced in May 2016 under the additional lease. Beginning in April 2019, annual rent under the initial lease, as amended by the Second Amendment, will be $2.1 million for the first twelve months, with annual increases of 2.0 percent thereafter. We have $1.5 million in restricted cash that is recorded in long-term other assets as of December 31, 2018 and 2017 in connection with an irrevocable standby letter of credit with RREEF. Our facility leases described above generally contain customary provisions allowing the landlords to terminate the leases if we fail to remedy a breach of any of our obligations under any such lease within specified time periods, or upon our bankruptcy or insolvency. Total rent expense, including operating expenses, under our real property leases was $40.6 million, $18.7 million and $15.9 million for the years ended December 31, 2018, 2017 and 2016, respectively. In addition to the lease agreements described above, we also lease additional office space in several locations in and outside of the U.S. to support our operations and growth. Future minimum payments under our non-cancelable facility leases, including rent payments for the BMR-675 West Kendall Lease which commenced in February 2019, are approximately as follows, in thousands: Year Ending December 31, 2019 $ 32,228 2020 34,826 2021 34,410 2022 34,826 2023 35,270 Thereafter 390,455 Total $ 562,015 Credit Agreements On April 29, 2016, we entered into (i) a Credit Agreement, or the BOA Credit Agreement, with Alnylam U.S., Inc., our wholly-owned subsidiary, as the borrower, us, as a guarantor, and Bank of America N.A., or BOA, as the lender and (ii) a Credit Agreement, or the Wells Credit Agreement, together with the BOA Credit Agreement, the Credit Agreements, by and among Alnylam U.S., Inc., as the borrower, us, as a guarantor, and Wells Fargo Bank, National Association, or Wells, as the lender. The Credit Agreements were entered into in connection with the planned build out of our new drug substance manufacturing facility. The BOA Credit Agreement provided for a $120.0 million term loan facility and was scheduled to mature on April 29, 2021. In December 2017, we repaid in full the $120.0 million outstanding principal amount under the BOA Credit Agreement and the BOA Credit Agreement terminated in accordance with its terms upon repayment of the outstanding indebtedness. The Wells Credit Agreement provides for a $30.0 million term loan facility and matures on April 29, 2021. The proceeds of the borrowing under the BOA Credit Agreement were, and under the Wells Credit Agreement are, to be used for working capital and general corporate purposes. Interest on borrowings under the BOA Credit Agreement was, and under the Wells Credit Agreement is calculated based on LIBOR plus 0.45 percent, except in the event of default. The borrower may prepay loans under the Wells Credit Agreement at any time, without premium or penalty, subject to certain notice requirements and LIBOR breakage costs. The obligations of the borrower and us under the BOA Credit Agreement were, and under the Wells Credit Agreement are secured by cash collateral in an amount equal to, at any given time, at least 100 percent of the principal amount of all term loans outstanding under such Credit Agreement at such time. At December 31, 2018 and 2017, we had recorded $30.0 million of cash collateral in connection with the Wells Credit Agreement as restricted investments on our consolidated balance sheets. The Wells Credit Agreement contains limited representations and warranties and limited affirmative and negative covenants, including quarterly reporting obligations, as well as certain customary events of default. Litigation From time to time, we are a party to legal proceedings in the course of our business, including the matters described below. The claims and legal proceedings in which we could be involved include challenges to the scope, validity or enforceability of patents relating to our product candidates, and challenges by us to the scope, validity or enforceability of the patents held by others. These include claims by third parties that we infringe their patents. The outcome of any such legal proceedings, regardless of the merits, is inherently uncertain. In addition, litigation and related matters are costly and may divert the attention of our management and other resources that would otherwise be engaged in other activities. If we were unable to prevail in any such legal proceedings, our business, results of operations, liquidity and financial condition could be adversely affected Silence Litigation In October 2017, Silence Therapeutics plc served its previously announced claim in the High Court of England and Wales, issued in the name of Silence Therapeutics GmbH, and together with Silence Therapeutics plc, referred to as Silence, against Alnylam UK Ltd., Alnylam Pharmaceuticals, Inc., and The Medicines Company UK Limited, seeking a declaration that Silence was entitled to a Supplementary Protection Certificate for Silence’s European Patent No. 2 258 847, when each of patisiran, fitusiran, givosiran and inclisiran obtained a marketing authorization in Europe. In June 2018, Silence withdrew this claim against both us and The Medicines Company UK Limited. Silence also withdrew its previously filed claim alleging infringement of its European Patent No. 1 857 547, referred to as the ‘547 patent, by fitusiran. Silence also served patent infringement proceedings against us in Portugal alleging that patisiran infringes the ‘547 patent as granted. Silence was seeking a permanent injunction against the commercialization of patisiran in Portugal. On October 10, 2018, Silence filed for Preliminary Relief with the District Court of The Hague, The Netherlands, related to its European Patent No. 3 222 724, referred to as the ‘724 patent, alleging that ONPATTRO infringes one or more claims of the ‘724 patent, seeking a cross-border preliminary injunction in those European countries where the patent has been validated On December 9, 2018, we and our wholly owned subsidiary, Alnylam UK Ltd. and Silence entered into a settlement and license agreement resolving all ongoing claims, administrative proceedings, and regulatory proceedings worldwide between the companies regarding, among other issues, patent infringement, patent invalidity and breach of contract, referred to collectively as the Proceedings. The terms of the settlement and license agreement include mutual releases and provide for the dismissal, withdrawal or discontinuation with prejudice of all claims and counterclaims in the Proceedings between the parties. Each party will bear its own attorney fees and costs incurred in the Proceedings. The settlement and license agreement does not include any admission of liability or wrongdoing by any party. Under terms of the settlement and license agreement, beginning on January 1, 2019 through 2023, Silence will be entitled to receive a low, tiered royalty ranging from 0.33 percent to 1.0 percent on annual net sales of ONPATTRO in the European Union, or EU, only. The settlement and license agreement includes the grant from Silence to us of a non-exclusive, global, irrevocable license, with the right to sublicense to affiliates and additional licensees (including our current and future collaborators and distributors), to all relevant patents for all current and future products of ours, whether commercialized by us or a collaborator or licensee (including without limitation ONPATTRO, vutrisiran, givosiran, lumasiran, inclisiran, fitusiran, cemdisiran, ALN-HBV02, ALN-AAT02, and all other investigational therapeutics in our current and future pipeline). Such license is fully paid up with no milestones or royalties, except for the limited royalty on ONPATTRO net sales in the EU only, as described above. Securities Litigation By stipulation of the parties and Order of the Court dated November 20, 2018, the action was transferred to the United States District Court for the District of Massachusetts. Motions for the appointment of lead plaintiff and lead counsel were required to be filed by November 26, 2018. There are three such motions currently pending. We anticipate the filing of an amended complaint following the Court’s appointment of lead plaintiff and lead counsel. We believe that the allegations contained in the complaint are without merit and intend to defend the case vigorously. We cannot predict at this point the length of time that this action will be ongoing or the liability, if any, which may arise therefrom. Dicerna Litigation On June 10, 2015, we filed a trade secret misappropriation lawsuit against Dicerna in the Superior Court of Middlesex County, Massachusetts seeking to stop misappropriation by Dicerna of our confidential, proprietary and trade secret information related to the RNAi assets we purchased from Merck, including certain N-acetylgalactosamine, or GalNAc, conjugate technology. In addition to permanent injunctive relief, we were also seeking monetary damages from Dicerna. In August 2017, Dicerna successfully added counterclaims against us in the trade secret lawsuit alleging that our lawsuit represented abuse of process and claiming tortious interference with its business. In September 2017, we filed a motion to dismiss Dicerna’s counterclaims, which motion was denied. In addition, in August 2017, Dicerna filed a lawsuit against us in the United States District Court of Massachusetts alleging attempted monopolization by us under the Sherman Antitrust Act. In October 2017, we filed a motion to dismiss the antitrust lawsuit. On April 18, 2018, we and Dicerna entered into a Settlement Agreement resolving all ongoing litigation between the companies. The terms of the Settlement Agreement include mutual releases and dismissal with prejudice of all claims and counterclaims in the following litigation between the parties: (i) Alnylam Pharmaceuticals, Inc. v. Dicerna Pharmaceuticals, Inc. Dicerna Pharmaceuticals, Inc. v. Alnylam Pharmaceuticals, Inc. Under the terms of the Settlement Agreement, Dicerna will pay us an aggregate of $25.0 million, including an upfront cash payment of $2.0 million and 983,208 shares of Dicerna common stock, valued at $10.0 million, that were received in the second quarter of 2018, and an additional $13.0 million due over the next four years, the timing of which was dependent upon revenue Dicerna received pursuant to future partnerships and collaborations related to GalNAc-conjugated RNAi research and development. As a result of Dicerna collaborations entered into subsequent to the Settlement Agreement, we were due the additional $13.0 million as of December 31, 2018, of which $2.5 million and $10.5 million was received in December 2018 and January 2019, respectively. In addition, Dicerna is restricted in its development and other activities relating to oligonucleotide-based therapeutics directed toward a defined set of targets, for periods ranging from 18 months up to four years. The Settlement Agreement does not include any license to our GalNAc conjugate intellectual property or any licenses to any other intellectual property from either party. Nor does the Settlement Agreement include any admission of liability or wrongdoing by either company. Indemnifications In connection with our license agreements with Max Planck relating to the Tuschl I and Tuschl II patent applications, we are required to indemnify Max Planck Gesellschaft zur Foerderung der Wissenschaften e.V., or Max Planck, for certain damages arising in connection with the intellectual property rights licensed under the agreements. Under the Max Planck indemnification agreement, we are responsible for paying the costs of any litigation relating to the license agreements or the underlying intellectual property rights, including the costs associated with certain litigation regarding the Tuschl patents, which was settled during 2011, as well as certain costs associated with defending prior litigation with the University of Utah, or Utah, which was fully resolved in 2017. In connection with the settlement of the litigation regarding the Tuschl patents, we also agreed to indemnify the Whitehead Institute for Biomedical Research, or Whitehead, Massachusetts Institute of Technology and the University of Massachusetts for certain costs associated with defending the Utah litigation. In connection with our research agreement with Acuitas Therapeutics Inc., or Acuitas (formerly AlCana Technologies, Inc.), we agreed to indemnify Acuitas for certain legal costs, subject to certain exceptions and limitations, associated with certain litigation with Arbutus, which has been settled. These indemnification costs were charged to selling, general and administrative expense. We are also a party to a number of agreements entered into in the ordinary course of business, which contain typical provisions that obligate us to indemnify the other parties to such agreements upon the occurrence of certain events. Such indemnification obligations are usually in effect from the date of execution of the applicable agreement for a period equal to the applicable statute of limitations. Our maximum potential future liability under any such indemnification provisions is uncertain. However, to date, other than certain costs associated with certain previously settled litigation related to the Tuschl patents and the litigation with Arbutus referenced above, and certain defense costs related to the Utah litigation described above, we have not incurred material costs to defend lawsuits or settle claims related to these indemnification provisions. We have determined that the estimated aggregate fair value of our potential liabilities under all such indemnification provisions is minimal and had not recorded any liability related to such indemnification provisions at December 31, 2018 or 2017.

STOCKHOLDERS' EQUITY

STOCKHOLDERS' EQUITY	12 Months Ended
	Dec. 31, 2018
Equity [Abstract]
STOCKHOLDERS' EQUITY	10 . STOCKHOLDERS’ EQUITY Preferred Stock We have authorized up to 5,000,000 shares of preferred stock, $0.01 par value per share, for issuance. The preferred stock will have such rights, preferences, privileges and restrictions, including voting rights, dividend rights, conversion rights, redemption privileges and liquidation preferences, as shall be determined by our board of directors upon its issuance. At December 31, 2018 and 2017, there were no shares of preferred stock outstanding. Public Offerings In January 2019, we sold an aggregate of 5,000,000 shares of our common stock through an underwritten public offering at a price to the public of $77.50 per share. As a result of the offering, we received aggregate net proceeds of $381.9 million, after deducting underwriting discounts and commissions and other estimated offering expenses of $5.6 million. In November 2017, we sold an aggregate of 6,440,000 shares of our common stock through an underwritten public offering at a price to the public of $125.00 per share. As a result of the offering, which included the full exercise of the underwriters’ option to purchase additional shares, we received aggregate net proceeds of $784.5 million, after deducting underwriting discounts and commissions and other offering expenses of $20.5 million. In May 2017, we sold an aggregate of 5,000,000 shares of our common stock through an underwritten public offering at a price to the public of $71.87 per share. As a result of the offering, we received aggregate net proceeds of $355.2 million, after deducting underwriting discounts and commissions and other offering expenses of $4.2 million.

STOCK-BASED COMPENSATION

STOCK-BASED COMPENSATION	12 Months Ended
	Dec. 31, 2018
Disclosure Of Compensation Related Costs Sharebased Payments [Abstract]
STOCK-BASED COMPENSATION	11 . STOCK-BASED COMPENSATION Stock Plans In June 2009, our stockholders approved our 2009 Stock Incentive Plan which was amended and restated in May 2015 with stockholder approval to increase the number of shares of common stock authorized for issuance from 5,900,000 to 11,700,000. In May 2017, our stockholders approved a second amendment and restatement of the 2009 Stock Incentive Plan, or the Second Amended and Restated 2009 Plan, which increased the number of shares of common stock authorized for issuance from 11,700,000 to 15,480,000. In May 2018, our stockholders approved our 2018 Stock Incentive Plan, or the 2018 Plan, which provides for the issuance of up to 3,500,000 shares in addition to the shares that remained available for grant under our Second Amended and Restated 2009 Plan as of May 10, 2018, the date of approval of the 2018 Plan by stockholders, and any shares underlying any awards granted under the Second Amended and Restated 2009 Plan that expire, or are terminated, surrendered or canceled without having been fully exercised or are forfeited in whole or in part after the date of our 2018 annual meeting. Consistent with the terms of the Second Amended and Restated 2009 Plan, the 2018 Plan provides for the granting of stock options, restricted stock and restricted stock units (together, restricted stock awards), stock appreciation rights and other stock-based awards, and has a fungible share pool. Any award that is not a full value award is counted against the authorized share limits specified as one share for each share of common stock subject to the award, and all full value awards, defined as restricted stock awards or other stock-based awards, are counted as one and a half shares for each one share of common stock subject to such full value award. At December 31, 2018, an aggregate of 17,491,117 shares of common stock were reserved for issuance under our stock plans, including outstanding stock options to purchase 12,572,522 shares of common stock, 36,083 outstanding restricted stock units, 4,433,370 of common stock available for additional equity awards and 449,142 shares available for future grant under our Amended and Restated 2004 Employee Stock Purchase Plan, or the Amended and Restated ESPP. Each stock option shall expire within ten years of issuance. Time-based stock options granted by us to employees generally vest as to 25 percent of the shares on the first anniversary of the grant date and 6.25 percent of the shares at the end of each successive three-month period thereafter until fully vested. Performance-based stock options granted to employees in 2013 and 2014 vested, with respect to each year, as to one-third of the shares upon the achievement of each of three specific clinical development or regulatory events, as approved by our compensation committee. Performance-based stock options granted to employees in 2015 and 2016 vest, with respect to each year, as to one-fourth of the shares upon the later of the one-year anniversary of the grant date and the achievement of each of four specific clinical development, regulatory or commercial events, as approved by our compensation committee. Historically, stock option awards to employees for annual performance, including performance-based stock option awards beginning in 2013, were approved for grant by the compensation committee of our board of directors at year-end. However, with respect to 2017 annual awards as well as future annual awards, our compensation committee intends to approve the grant of any such awards in the first quarter of the following year. For example, on March 1, 2018, our compensation committee approved performance-based stock options with respect to 2017 annual awards that vest, as to one-third of the shares upon the later of the one-year anniversary of the grant date and the achievement of each of three specific clinical development, regulatory or commercial events, as approved by our compensation committee. Change in Control Agreements On November 7, 2017, we entered into a Change in Control, or CIC, Agreement with each member of our management board. If a member of our management board is terminated by us without Cause, as defined in the CIC Agreement, or if a management board member terminates his or her employment for Good Reason, as defined in the CIC Agreement, in either case, within 12 months following a CIC, such management board member will be entitled to receive certain benefits, including the immediate acceleration of all outstanding unvested stock options and other stock-based awards. In accordance with accounting guidance for stock-based compensation expense, we expect to record the modification date fair value for any equity grants that were not considered probable of vesting as of November 7, 2017 that ultimately vest. During the years ended December 31, 2018 and 2017, we recorded $20.8 million and $1.1 million, respectively, related to this modification. Inducement Equity Grants Effective as of each of May 8, 2017 and September 19, 2016, respectively, our compensation committee approved a grant to a newly hired executive of non-qualified stock options to purchase an aggregate of 150,000 shares of common stock. For each executive, time-vested options to purchase 125,000 shares of common stock will vest as to 25 percent of the shares on the first anniversary of the respective grant date and 6.25 percent of the shares at the end of each successive three-month period thereafter until fully vested. For each executive, performance-based stock options to purchase 25,000 shares of common stock were subject to vest upon the later of the one-year anniversary of the respective grant date and the launch of our first internally developed product, the achievement of which occurred in the third quarter of 2018. In addition, effective as of February 6, 2017, our compensation committee approved a grant to a newly hired vice president level employee, of non-qualified stock options to purchase an aggregate of 50,000 shares of common stock. This time-vested option grant will vest as to 25 percent of the shares on the first anniversary of the grant date and 6.25 percent of the shares at the end of each successive three-month period thereafter until fully vested. Each of the May 8, 2017, February 6, 2017 and September 19, 2016 option award was granted as an inducement grant outside of our stockholder approved stock plans in accordance with Nasdaq Listing Rule 5635(c)(4). Each of these stock options has a ten-year term and an exercise price equal to the closing price of our common stock on the respective grant date. Stock-Based Compensation The following table summarizes stock-based compensation expense during the three years ended December 31, 2018, in thousands: 2018 2017 2016 Stock-based compensation expense by type of award: Time-based stock options $ 83,403 $ 61,802 $ 62,800 Performance-based stock options 56,419 23,260 8,337 Time-based restricted stock units 538 541 497 Performance-based restricted stock units 13,144 — — ESPP share issuances 2,842 2,155 1,360 Other equity programs 1,345 1,946 1,846 Non-employee stock options 1,485 3,115 688 Less: Stock-based compensation expense capitalized to inventory (1,424 ) — — $ 157,752 $ 92,819 $ 75,528 The following table summarizes our unrecognized stock-based compensation expense, net of estimated forfeitures, at December 31, 2018 by type of awards, and the weighted-average period over which that expense is expected to be recognized: At December 31, 2018 Unrecognized Expense, Net of Estimated Forfeitures Weighted- average Recognition Period (in thousands) (in years) Type of award: Time-based stock options $ 156,192 2.53 Performance-based stock options 57,586 * Time-based restricted stock units 769 0.78 Performance-based restricted stock units 1,747 * ESPP share issuances 984 0.33 * Performance-based stock options and performance-based restricted stock units are recorded as expense beginning when vesting events are determined to be probable. Valuation Assumptions for Stock Options The fair value of stock options, at date of grant, based on the following assumptions, was estimated using the Black-Scholes option-pricing model. Our expected stock-price volatility assumption is based on the historical volatility of our publicly traded stock. The expected life assumption is based on our historical data. The dividend yield assumption is based on the fact that we have never paid cash dividends and have no present intention to pay cash dividends. The risk-free interest rate used for each grant is equal to the zero coupon rate for instruments with a similar expected life. 2018 2017 2016 Risk-free interest rate 2.7-2.9% 1.9-2.3% 0.9-2.2% Expected dividend yield — — — Expected option life 5.7-7.2 years 5.7-7.2 years 3.5-7.5 years Expected volatility 64-67% 61-67% 55-65% Stock Option Activity The following table summarizes the activity of our stock option plans and the inducement grants described above, excluding performance-based stock options: Number of Options (in Weighted- average Exercise Price Weighted- average Remaining Contractual Term (in years) Aggregate Intrinsic Value (in thousands) Outstanding, December 31, 2017 9,101 $ 60.18 Granted 2,273 110.11 Exercised (1,181 ) 46.92 Cancelled (364 ) 82.89 Outstanding, December 31, 2018 9,829 $ 72.48 6.68 $ 149,518 Exercisable at December 31, 2018 5,734 $ 58.90 5.31 $ 127,051 Vested or expected to vest at December 31, 2018 9,327 $ 71.36 6.56 $ 147,144 The weighted-average fair value of stock options granted was $66.49, $44.76 and $31.66 per share for the years ended December 31, 2018, 2017 and 2016, respectively. The intrinsic value of stock options exercised was $87.1 million, $111.3 million and $22.0 million for the years ended December 31, 2018, 2017 and 2016, respectively. We satisfy stock option exercises with newly issued shares of our common stock. Performance-Based Stock Options With respect to the performance-based portion of the annual stock option awards, a portion of the shares subject to the performance-based stock option will vest upon the later of the one-year anniversary of the date of grant and the achievement of specific clinical development, regulatory and/or commercial events, as approved by our compensation committee. During each of the years ended December 31, 2017 and 2016, we also granted an option to purchase 25,000 shares of common stock to a newly hired executive that were subject to vest upon the later of the one-year anniversary of the grant date and the achievement of a commercial event. The following table summarizes the activity of our performance-based stock options granted under our equity plans and the performance-based portion of the inducement grants described above: Number of Options (in Weighted- average Exercise Price Weighted- average Remaining Contractual Term (in years) Aggregate Intrinsic Value (in thousands) Outstanding, December 31, 2017 2,138 $ 69.14 Granted 912 119.13 Exercised (149 ) 67.04 Cancelled (157 ) 88.64 Outstanding, December 31, 2018 2,744 $ 84.75 7.24 $ 23,694 Exercisable at December 31, 2018 1,420 $ 74.29 6.21 $ 13,134 During the years ended December 31, 2018, 2017 and 2016, there were 763,982, 614,796 and 159,122 performance-based stock options that vested, respectively. The intrinsic value of performance-based stock options exercised was $8.0 million, $1.8 million and $35,000 for the years ended December 31, 2018, 2017 and 2016, respectively. We satisfy performance-based stock option exercises with newly issued shares of our common stock. During the years ended December 31, 2018, 2017 and 2016, for each performance-based stock option that was determined to be probable of vesting, we began to record expense during the year. In addition, as of December 31, 2018, we had determined that certain stock option awards vesting upon the achievement of commercial sales targets were probable of achievement and we began to record stock-based compensation expense during the second half of 2018 following the approval and launch of ONPATTRO . Performance-Based Restricted Stock Units In January 2016, we granted 172,718 shares of performance-based restricted stock units to certain employees, excluding our chief executive officer and president. These performance-based restricted stock units were valued at $16.1 million on the grant date. The vesting of these performance-based restricted stock units was predicated on the launch of our first internally developed product, which was achieved in August 2018. As of the grant date and until we received regulatory approval from the FDA for ONPATTRO on August 10, 2018, for accounting purposes we had determined that the performance criteria for these performance-based restricted stock units was not probable of being achieved. As a result, we recorded the total stock-based compensation expense of $11.8 million for the 124,833 performance-based restricted stock units that vested upon the launch of ONPATTRO during August 2018. The total fair value of these performance-based restricted stock units that vested (measured on the date of vesting) was $11.4 million. Employee Stock Purchase Plan In 2004, we adopted the 2004 Employee Stock Purchase Plan with 315,789 shares authorized for issuance. In June 2010, our stockholders approved an amendment to the 2004 Employee Stock Purchase Plan, which increased the shares authorized for issuance from 315,789 shares to 715,789 shares. In May 2017, our stockholders approved the Amended and Restated ESPP, which further increased the shares authorized for issuance from 715,789 shares to 1,215,789 shares. Under the Amended and Restated ESPP, each offering period is six months, at the end of which employees may purchase shares of common stock through payroll deductions made over the term of the offering. The per-share purchase price at the end of each offering period is equal to the lesser of 85 percent of the closing price of our common stock at the beginning or end of the offering period. We issued 78,085, 103,666 and 53,499 shares during the years ended December 31, 2018, 2017 and 2016, respectively, and at December 31, 2018, 449,142 shares were available for issuance under the Amended and Restated ESPP. The weighted-average fair value of stock purchase rights granted as part of the Amended and Restated ESPP was $35.67, $17.10 and $24.90 per share for the years ended December 31, 2018, 2017 and 2016, respectively. The fair value was estimated using the Black-Scholes option-pricing model. During the year ended December 31, 2018, we used a weighted-average stock-price volatility of 63 percent, expected option life assumption of six months and a risk-free interest rate of 2 percent. During the year ended December 31, 2017, we used a weighted-average stock-price volatility of 91 percent, expected option life assumption of six months and a risk-free interest rate of 0.7 percent. During the year ended December 31, 2016, we used a weighted-average stock-price volatility of approximately 55 percent, expected option life assumption of six months and a risk-free interest rate of approximately 0.1 percent.

INCOME TAXES

INCOME TAXES	12 Months Ended
	Dec. 31, 2018
Income Tax Disclosure [Abstract]
INCOME TAXES	1 2 . INCOME TAXES The domestic and foreign components of loss before income taxes are as follows, in thousands: 2018 2017 2016 Domestic $ (573,245 ) $ (378,293 ) $ (350,704 ) Foreign (187,429 ) (112,581 ) (59,404 ) Loss before income taxes $ (760,674 ) $ (490,874 ) $ (410,108 ) The provision for income taxes for each of the years ended December 31, 2018, 2017 and 2016 consisted of the following: 2018 2017 2016 Current provision: Domestic $ — $ — $ — Foreign (1,611 ) — — Total current provision (1,611 ) — — Deferred benefit: Federal 788 — — Foreign — — — Total deferred benefit 788 — — Total provision for income taxes $ (823 ) $ — $ — Deferred income taxes reflect the tax effects of temporary differences between the carrying amounts of assets and liabilities for financial reporting and income tax purposes. We establish a valuation allowance when uncertainty exists as to whether all or a portion of the net deferred tax assets will be realized. Components of the net deferred tax (liability) asset at December 31, 2018 and 2017 are as follows, in thousands: 2018 2017 Deferred tax assets: Net operating loss carryforwards $ 506,574 $ 405,784 Research and development and ODC credits 220,776 192,094 AMT credits 788 788 Capitalized research and development and start-up costs 12,139 13,163 Deferred revenue — 13,576 Deferred compensation 57,268 42,990 Property, plant and equipment, net — 2,471 Intangible assets 50,121 9,018 Other 20,660 9,137 Total deferred tax assets 868,326 689,021 Deferred tax liabilities: Property, plant and equipment, net (6,550 ) — Unrealized gain on marketable securities (903 ) (765 ) Deferred tax asset valuation allowance (860,085 ) (688,256 ) Net deferred tax asset $ 788 $ — Our effective income tax rate differs from the statutory federal income tax rate as follows for the years ended December 31, 2018, 2017 and 2016: 2018 2017 2016 At U.S. federal statutory rate 21.0 % 35.0 % 35.0 % State taxes, net of federal effect 2.1 3.8 3.7 Stock-based compensation 0.8 3.3 (1.4 ) Tax credits 4.2 9.9 11.8 Orphan drug credit — (3.4 ) (3.5 ) Other permanent items (0.3 ) (1.0 ) (0.4 ) Foreign rate differential (5.3 ) (8.1 ) (5.1 ) Tax reform change — (46.5 ) — Revaluation of deferred credits due to rate change (3.5 ) — — Other — (0.9 ) — Valuation allowance (19.0 ) 7.9 (40.1 ) Effective income tax rate — % — % — % We have evaluated the positive and negative evidence bearing upon the realizability of our deferred tax assets. We have concluded, in accordance with the applicable accounting standards, that it is more likely than not that we may not realize the benefit of all of our deferred tax assets, with the exception of the deferred asset related to alternative minimum tax credits as these have become refundable over the following four years. Accordingly, we have recorded a valuation allowance against the deferred tax assets that management believes will not be realized. We re-evaluate the positive and negative evidence on a quarterly basis. The valuation allowance increased by $171.8 million, $112.9 million and $177.9 million for the years ended December 31, 2018, 2017 and 2016, respectively, due primarily to additional operating losses. During the year ended December 31, 2018, we recorded a net provision for income taxes of $0.8 million related to $1.6 million due to foreign income taxes recorded during the year ended December 31, 2018 partially offset by a $0.8 million benefit for refundable credits related to the TCJA. There was no provision for income taxes recorded during the years ended December 31, 2017 or 2016. At December 31, 2018, we had federal and state net operating loss carryforwards of $1.9 billion and $1.6 billion, respectively, to reduce future taxable income that will expire at various dates through 2038. At December 31, 2018, approximately $0.5 billion of our federal net operating loss carryforward can be carried forward indefinitely. At December 31, 2018, we had federal and state research and development, including Orphan Drug, and state investment tax credit carryforwards of $208.0 million and $16.2 million, respectively, available to reduce future tax liabilities that expire at various dates through 2038. At December 31, 2018, we had alternative minimum tax credits of $0.8 million that will either be available to reduce future regular tax liabilities or be fully refundable in 2021. We have a valuation allowance against the net operating loss and credit deferred tax assets as it is unlikely that we will realize these assets. Ownership changes, as defined in the Internal Revenue Code, including those resulting from the issuance of common stock in connection with our public offerings, may limit the amount of net operating loss and tax credit carryforwards that can be utilized to offset future taxable income or tax liability. The amount of the limitation is determined in accordance with Section 382 of the Internal Revenue Code. We have performed an analysis of ownership changes through December 31, 2018. Based on this analysis, we do not believe that any of our tax attributes will expire unutilized due to Section 382 limitations. At December 31, 2018, 2017 and 2016, we had no unrecognized tax benefits and have recorded no interest and penalties since inception, accordingly. The tax years 2015 through 2018 remain open to examination by major taxing jurisdictions to which we are subject, which are primarily in the U.S., as carryforward attributes generated in years past may still be adjusted upon examination by the Internal Revenue Service or state tax authorities if they have or will be used in a future period.

ACCRUED EXPENSES

ACCRUED EXPENSES	12 Months Ended
	Dec. 31, 2018
Accrued Liabilities Current [Abstract]
ACCRUED EXPENSES	1 3 . ACCRUED EXPENSES Accrued expenses consist of the following at December 31, 2018 and 2017, in thousands: At December 31, 2018 2017 Compensation and related $ 37,301 $ 33,826 Clinical trial and manufacturing 36,500 20,004 Consulting and professional services 10,450 7,276 Product revenue allowances 2,696 — Pre-clinical 2,138 239 Other 23,634 10,858 $ 112,719 $ 72,203

QUARTERLY FINANCIAL DATA (UNAUD

QUARTERLY FINANCIAL DATA (UNAUDITED)	12 Months Ended
	Dec. 31, 2018
Quarterly Financial Information Disclosure [Abstract]
QUARTERLY FINANCIAL DATA (UNAUDITED)	1 4 . QUARTERLY FINANCIAL DATA (UNAUDITED) The following information has been derived from unaudited consolidated financial statements that, in the opinion of management, include all recurring adjustments necessary for a fair statement of such information. Three Months Ended March 31, 2018 June 30, 2018 September 30, 2018 December 31, 2018 (In thousands, except per share data) Revenues $ 21,899 $ 29,907 $ 2,069 $ 21,033 Operating costs and expenses 169,304 222,261 256,627 241,389 Net loss $ (141,214 ) $ (163,560 ) $ (245,282 ) $ (211,441 ) Net loss per common share — basic and diluted $ (1.41 ) $ (1.63 ) $ (2.43 ) $ (2.09 ) Weighted-average common shares — basic and diluted 99,979 100,519 100,783 101,066 Three Months Ended March 31, 2017 June 30, 2017 September 30, 2017 December 31, 2017 (In thousands, except per share data) Revenues $ 18,960 $ 15,932 $ 17,096 $ 37,924 Operating costs and expenses 125,471 136,406 142,896 185,227 Net loss $ (107,290 ) $ (118,420 ) $ (122,937 ) $ (142,227 ) Net loss per common share — basic and diluted $ (1.25 ) $ (1.34 ) $ (1.34 ) $ (1.48 ) Weighted-average common shares — basic and diluted 86,027 88,098 91,828 96,139 On January 1, 2018, we adopted the new revenue standard by applying the modified retrospective method to all contracts that were not completed as of January 1, 2018. Please read Note 2 for further discussion of our adoption of the new revenue standard.

SUMMARY OF SIGNIFICANT ACCOUN_2

SUMMARY OF SIGNIFICANT ACCOUNTING POLICIES (Policies)	12 Months Ended
	Dec. 31, 2018
Accounting Policies [Abstract]
Basis of Presentation and Principles of Consolidation	Basis of Presentation and Principles of Consolidation The accompanying consolidated financial statements reflect the operations of Alnylam and our wholly-owned subsidiaries. All intercompany accounts and transactions have been eliminated.
Use of Estimates	Use of Estimates The preparation of financial statements in conformity with accounting principles generally accepted in the United States of America, or
Liquidity	Liquidity Based on our current operating plan, we believe that our cash, cash equivalents and marketable debt securities at December 31, 2018, together with the cash we expect to generate from product sales and under our current alliances, will be sufficient to enable us to advance our Alnylam 2020
Concentrations of Credit Risk and Significant Customers	Concentrations of Credit Risk and Significant Customers Financial instruments that potentially expose us to concentrations of credit risk consist primarily of cash, cash equivalents and marketable debt securities. At December 31, 2018 and 2017, substantially all of our cash, cash equivalents and marketable debt securities were invested in money market funds, certificates of deposit, commercial paper, corporate notes, U.S. government-sponsored enterprise securities and U.S. treasury securities through highly rated financial institutions. Corporate notes may also include foreign bonds denominated in U.S. dollars. Investments are restricted, in accordance with our investment policy, to a concentration limit per issuer. In recent periods, our revenues have been generated primarily from collaborations with strategic partners, including Sanofi Genzyme, the specialty care global business unit of Sanofi, Vir Biotechnology, Inc., or Vir, and The Medicines Company, or MDCO. We began to record product revenues in the second half of 2018 following the approval of ONPATTRO by the The following table summarizes customers that represent greater than 10 percent of our consolidated total gross revenues for the periods indicated: Year Ended December 31, 2018 2017 2016 Sanofi Genzyme 58 % 61 % 68 % Vir Biotechnology 16 % * N/A Distributor A 13 % N/A N/A MDCO * 34 % 24 % * Represents 10 percent or less The following table summarizes customers with amounts due that represent greater than 10 percent of our gross accounts receivable balance, at the periods indicated: At December 31, 2018 2017 Distributor A 44 % N/A Sanofi Genzyme 29 % 39 % MDCO * 59 % * Represents 10 percent or less
Fair Value Measurements	Fair Value Measurements The fair value is the price that would be received to sell an asset or paid to transfer a liability in an orderly transaction between market participants at the measurement date. In general, fair values determined by Level 1 inputs utilize quoted prices (unadjusted) in active markets for identical assets or liabilities. Fair values determined by Level 2 inputs utilize data points that are observable, such as quoted prices (adjusted), interest rates and yield curves. Fair values determined by Level 3 inputs utilize unobservable data points for the asset or liability, and include situations where there is little, if any, market activity for the asset or liability. The fair value hierarchy level is determined by the lowest level of significant input.
Investments in Marketable Securities and Cash Equivalents	Investments in Marketable Securities and Cash Equivalents We invest our excess cash balances in short-term and long-term marketable debt securities. We classify our investments in marketable debt securities as either held-to-maturity or available-for-sale based on facts and circumstances present at the time we purchased the securities. At each balance sheet date presented, we classified all of our investments in debt securities as available-for-sale. We report available-for-sale debt securities at fair value at each balance sheet date and include any unrealized holding gains and losses (the adjustment to fair value) in accumulated other comprehensive income (loss), a component of stockholders’ equity. At December 31, 2018, the balance in our accumulated other comprehensive loss was composed solely of activity related to our marketable debt securities and our investment in equity securities of Regulus Therapeutics Inc., or Regulus. Realized gains and losses are determined using the specific identification method and are included in other income (expense). We did not recognize any realized gains or losses from sales of our available-for-sale debt securities during the years ended December 31, 2018, 2017 or 2016, and as a result, did not reclassify any amount out of accumulated other comprehensive loss for the respective period related to our available-for-sale debt securities. If any adjustment to fair value reflects a decline in the value of the marketable debt securities, we consider all available evidence to evaluate the extent to which the decline is “other than temporary,” including our intention to sell and, if so, mark the investment to market through a charge to our consolidated statements of comprehensive loss. We did not record any impairment charges related to our marketable debt securities during the years ended December 31, 2018, 2017 or 2016. Our marketable debt securities are classified as cash equivalents if the original maturity, from the date of purchase, is 90 days or less, and as marketable debt securities if the original maturity, from the date of purchase, is in excess of 90 days. Our cash equivalents are generally composed of commercial paper, corporate notes, U.S. government-sponsored enterprise securities, U.S. treasury securities and money market funds. Upon the adoption of the new accounting standard, discussed below under the heading “Recent Accounting Pronouncements,” effective January 1, 2018, we measure marketable equity investments (except those accounted for under the equity method of accounting or those that result in consolidation of an investee), which have readily available prices, at fair value with changes in fair value recognized in other income (expense) on our consolidated statements of comprehensive loss During the second quarter of 2017, we sold all our remaining holdings in Regulus. We accounted for our investment in Regulus as an available-for-sale marketable equity security. We recognized $1.9 million of realized losses and $7.0 million of realized gains from sales of our Regulus available-for-sale securities as other income (expense) in our consolidated statement of comprehensive loss during the year ended December 31, 2017 and 2016, respectively. Intraperiod tax allocation rules require us to allocate our provision for income taxes between continuing operations and other categories of earnings, such as other comprehensive income. In periods in which we have a year-to-date pre-tax loss from continuing operations and pre-tax income in other categories of earnings, such as other comprehensive income, we must allocate the tax provision to the other categories of earnings. We then record a related tax benefit in continuing operations. Upon sales of our marketable equity securities, we apply the aggregate portfolio approach to recognize the related tax provision or benefit into income (loss) from continuing operations. As a result, the disproportionate tax effect remains in accumulated other comprehensive income (loss) as long as we maintain an investment portfolio. At December 31, 2018 and 2017, there was $32.8 million of accumulated other comprehensive loss, net of tax, recorded on our consolidated balance sheets related to our investment in Regulus.
Accounts Receivable	Accounts Receivable We record accounts receivable net of customer allowances for distribution services, prompt payment discounts and chargebacks based on contractual terms. As of December 31, 2018, we determined an allowance for doubtful accounts was not required based upon our review of contractual payment terms and individual customer circumstances. We have standard payment terms that generally require payment within approximately 30 to 50 days. Accounts receivable, net on our consolidated balance sheets also includes billed and unbilled collaboration receivables.
Inventory	Inventory Prior to initial regulatory approval, we expense costs relating to the production of inventory as research and development expenses on our consolidated statements of comprehensive loss in the period incurred, unless we believe regulatory approval and subsequent commercialization of the product candidate is probable and we expect the future economic benefit from sales of the product to be realized, at which point we capitalize the costs as inventory. Inventory is measured at the lower of cost or estimated net realizable value. We use a standard cost basis, which approximates average cost determined on a first-in, first-out basis. Inventory costs include all raw materials, direct conversion costs and overhead. Raw and intermediate materials that may be used for either research and development or commercial purposes are classified as inventory until the material is consumed or otherwise allocated for research and development. If the material is used for research and development, it is expensed as research and development once that determination is made. We capitalize inventory costs that are expected to be sold commercially once we determine there is a high probability that the inventory costs will be recovered through commercial sale based on the review of several factors, including (i) the likelihood that all required regulatory approvals will be obtained, (ii) the expected timing of validation of manufacturing processes in the associated facility (if not yet completed), (iii) the expected expiration of the inventory, (iv) logistical or commercial constraints that may impede the timely distribution and sale of the product, including transport requirements and reimbursement status, (v) the history of approvals of similar products or formulations, and (vi) potential legal challenges. We reduce our inventory to net realizable value for potentially excess, dated or obsolete inventory based on our quarterly assessment of the recoverability of our capitalized inventory. Through December 31, 2018, we had not identified any impairment of our capitalized inventory.
Property, Plant and Equipment	Property, Plant and Equipment Property, plant and equipment are stated at cost, net of accumulated depreciation. Depreciation expense is recorded on a straight-line basis over the estimated useful life of the asset. Leasehold improvements are amortized over the shorter of the asset’s estimated useful life or the lease term. Construction in progress reflects amounts incurred for construction or improvements of property, plant or equipment that have not been placed in service. Costs of construction of certain long-lived assets include capitalized interest, which is amortized over the estimated useful life of the related asset. The cost and accumulated depreciation of assets retired or sold are removed from the respective asset category, and any gain or loss is recognized in our consolidated statements of comprehensive loss. The estimated useful lives of property, plant and equipment are as follows: Asset Category Useful Life Laboratory equipment 5 years Computer equipment and software 3-10 years Furniture and fixtures 5 years Leasehold improvements Shorter of asset life or lease term Land — Construction in progress —
Estimated Liability for Development Costs	Estimated Liability for Development Costs We record accrued liabilities related to expenses for which service providers have not yet billed us with respect to products we have received or services that we have incurred, specifically related to ongoing pre-clinical studies and clinical trials. These costs primarily relate to third-party clinical management costs, laboratory and analysis costs, toxicology studies and investigator fees. We have multiple product candidates in concurrent pre-clinical studies and clinical trials at multiple clinical sites throughout the world. In order to ensure that we have adequately provided for ongoing pre-clinical and clinical development costs during the period in which we incur such costs, we maintain an accrual to cover these expenses. We update the estimate for this accrual on at least a quarterly basis. The assessment of these costs is a subjective process that requires judgment. Upon settlement, these costs may differ materially from the amounts accrued in our consolidated financial statements. Our historical accrual estimates have not been materially different from our actual costs.
Revenue Recognition	Revenue Recognition We began to record revenues from product sales in the third quarter of 2018 subsequent to the approval of ONPATTRO by the FDA in August 2018. Prior to the third quarter of 2018, all of our revenues were derived from collaboration agreements that we have entered into with leading pharmaceutical and life sciences companies, including Sanofi Genzyme and MDCO. The terms of our collaboration agreements may include consideration such as non-refundable license fees, funding of research and development services, payments due upon the achievement of clinical and pre-clinical performance-based development milestones, regulatory milestones, manufacturing services, sales-based milestones and royalties on product sales. On January 1, 2018, we adopted the new revenue standard, discussed below under the heading “Recent Accounting Pronouncements,” which amended revenue recognition principles and provides a single, comprehensive set of criteria for revenue recognition within and across all industries. Our adoption of the new revenue standard had a material impact on our consolidated financial statements, as discussed below under the heading “Recent Accounting Pronouncements.” This new revenue standard applies to all contracts with customers, except for contracts that are within the scope of other standards, such as leases, insurance, collaboration arrangements and financial instruments. The new revenue standard provides a five-step framework whereby revenue is recognized when control of promised goods or services is transferred to a customer at an amount that reflects the consideration to which the entity expects to be entitled in exchange for those goods or services. To determine revenue recognition for arrangements that we determine are within the scope of the new revenue standard, we perform the following five steps: (i) identify the contract(s) with a customer; (ii) identify the performance obligations in the contract; (iii) determine the transaction price; (iv) allocate the transaction price to the performance obligations in the contract; and (v) recognize revenue when (or as) we satisfy a performance obligation. We only apply the five-step model to contracts when collectability of the consideration to which we are entitled in exchange for the goods or services we transfer to the customer is determined to be probable. At contract inception, once the contract is determined to be within the scope of the new revenue standard, we assess whether the goods or services promised within each contract are distinct and, therefore, represent a separate performance obligation. Goods and services that are determined not to be distinct are combined with other promised goods and services until a distinct bundle is identified. We then allocate the transaction price (the amount of consideration we expect to be entitled to from a customer in exchange for the promised goods or services) to each performance obligation and recognize the associated revenue when (or as) each performance obligation is satisfied. Our estimate of the transaction price for each contract includes all variable consideration to which we expect to be entitled. Amounts are recorded as accounts receivable when our right to consideration is unconditional. We do not assess whether a contract has a significant financing component if the expectation at contract inception is that the period between payment by the customer and the transfer of the promised goods or services to the customer will be one year or less. We expense incremental costs of obtaining a contract as and when incurred if the expected amortization period of the asset that we would have recognized is one year or less or the amount is immaterial. At December 31, 2018, we had not capitalized any costs to obtain any of our contracts. Product revenues, net In the third quarter of 2018, following FDA approval in August 2018, we began to ship ONPATTRO in the U.S. to specialty pharmacies, or SPs, and a specialty distributor, or SD, referred to as our customers. Our U.S. customers subsequently resell ONPATTRO to health care providers. We also received approval from the EC in August 2018 and launched ONPATTRO in several countries in Europe during the fourth quarter of 2018, where we primarily sell to government-owned and supported customers, including hospitals. The following are the components of variable consideration related to product revenues. We record reserves, based on contractual terms, for these components related to product sold during the reporting period, as well as our estimate of product that remains in the distribution channel inventory at the end of the reporting period that we expect will be sold to qualified healthcare providers. On a quarterly basis, we will update our estimates and record any needed adjustments in the period we identify the adjustments. Chargebacks: We estimate obligations resulting from contractual commitments with the government and other entities to sell products to qualified healthcare providers at prices lower than the list prices charged to the SD who purchases ONPATTRO from us. The SD charges us for the difference between what the SD pays to us for the product and the selling price to the qualified healthcare providers. Rebates : We are subject to discount obligations under government programs, including Medicaid in the U.S. and similar programs in certain countries in Europe. We are also subject to potential rebates in connection with our value-based agreements with certain commercial payors. We record reserves for rebates in the same period the related product revenue is recognized, resulting in a reduction of ONPATTRO product revenues and a current liability that is included in accrued expenses on our consolidated balance sheet. Our estimate for rebates is based on statutory discount rates and expected utilization. Trade discounts and allowances: We provide customary invoice discounts on ONPATTRO sales to our customers for prompt payment and we pay fees for distribution services, such as fees for certain data that customers provide to us. We estimate our customers will earn these discounts and fees, and deduct these discounts and fees in full from gross ONPATTRO revenues and accounts receivable at the time we recognize the related revenues. Product returns: ONPATTRO may be returned if it is damaged, defective or expired, with “expired” defined as having three months or less to expiry or within three months past expiry. We estimate the amount of product that will be returned using a probability-weighted estimate, initially calculated based on a portfolio of data from similar products and industry experience for SP products. Based on the distribution model for ONPATTRO, contractual inventory limits with our customers, the price of ONPATTRO and limited contractual return rights, we believe there will be minimal ONPATTRO returns. We have recorded an initial refund liability for our estimate of ONPATTRO returns related to sales during the year ended December 31, 2018. We will update our estimated refund liability, on at least a quarterly basis, based on actual shipments of ONPATTRO subject to contractual return rights, changes in expectations about the amount of estimated refunds or actual returns, as data is known Other incentives: Other incentives include co-payment assistance we provide to patients with commercial insurance that have coverage and reside in states that allow co-payment assistance. We estimate the average co-payment assistance amounts for ONPATTRO based on expected customer demographics and record any such amounts within accrued expenses on our consolidated balance sheet. Revenues from Collaborators We recognize the transaction price allocated to upfront license payments as revenue upon delivery of the license to the customer and resulting ability of the customer to use and benefit from the license, if the license is determined to be distinct from the other performance obligations identified in the contract. we exercise judgment to assess the nature of the combined performance obligation to determine whether the combined performance obligation is satisfied (i) at a point in time, but only for licenses determined to be distinct from other performance obligations in the contract, or (ii) over time; and, if over time, the appropriate method of measuring progress for purposes of recognizing revenue from license payments. We evaluate the measure of progress each reporting period and, if necessary, adjust the measure of performance and related revenue recognition. Many of our collaboration agreements entitle us to additional payments upon the achievement of performance-based milestones. These milestones are generally categorized into three types: development milestones, which are generally based on the advancement of our pipeline and initiation of clinical trials; regulatory milestones, which are generally based on the submission, filing or approval of regulatory applications such as an NDA in the U.S.; and sales-based milestones, which are generally based on meeting specific thresholds of sales in certain geographic areas. For each collaboration that includes development milestone payments, we evaluate whether it is probable that the consideration associated with each milestone will not be subject to a significant reversal in the cumulative amount of revenue recognized. Amounts that meet this threshold are included in the transaction price using the most likely amount method, whereas amounts that do not meet this threshold are considered constrained and excluded from the transaction price until they meet this threshold. At the end of each subsequent reporting period, we re-evaluate the probability of a significant reversal of the cumulative revenue recognized for our milestones, and, if necessary, adjust our estimate of the overall transaction price. Any such adjustments are recorded on a cumulative catch-up basis, which would affect revenues from collaborators and loss in the period of adjustment. have not recognized any royalty revenue resulting from any of our agreements. The new revenue standard, which was adopted in January 2018, requires us to allocate the arrangement consideration on a relative standalone selling price basis for each performance obligation after determining the transaction price of the contract and identifying the performance obligations to which that amount should be allocated. The relative standalone selling price is defined in the new revenue standard as the price at which an entity would sell a promised good or service separately to a customer. If other observable transactions in which we have sold the same performance obligation separately are not available, we are required to estimate the standalone selling price of each performance obligation. Key assumptions to determine the standalone selling price may include forecasted revenues, development timelines, reimbursement rates for personnel costs, discount rates and probabilities of technical and regulatory success. Whenever we determine that a contract should be accounted for as a combined performance obligation over time, we determine the period over which the performance obligations will be performed and revenue will be recognized. Revenue is recognized using a cost-to-cost input model. Direct labor hours or full-time equivalents are typically used as the measure of performance. Significant management judgment is required in determining the level of effort required under an arrangement and the period over which we are expected to complete our performance obligations under an arrangement. We evaluate our collaborative agreements for proper classification in our consolidated statements of comprehensive loss based on the nature of the underlying activity. Transactions between collaborators recorded in our consolidated statements of comprehensive loss are recorded on either a gross or net basis, depending on the characteristics of the collaborative relationship. We generally reflect amounts due under our collaborative agreements related to cost-sharing of development activities as revenue if we have a vendor-customer relationship with our collaborator. Costs incurred or shared with our collaboration partners that are deemed to be joint-risk sharing activities are recorded as an adjustment to the related operating expense captions. For revenue generating arrangements where we, as a vendor, provide consideration to a licensor or collaborator, as a customer, we apply the accounting standard that governs such transactions. This standard addresses the accounting for revenue arrangements where both the vendor and the customer make cash payments to each other for services and/or products. A payment to a customer is presumed to be a reduction of the transaction price unless we receive an identifiable benefit for the payment and we can reasonably estimate the fair value of the benefit received. Payments to a customer that are deemed a reduction of the transaction price are recorded first as a reduction of revenue, to the extent of both cumulative revenue recorded to date and probable future revenues, which include any unamortized deferred revenue balances, under all arrangements with such customer, and then as an expense. Payments that are not deemed to be a reduction of the transaction price are recorded as an expense. Consideration that does not meet the requirements to satisfy the above revenue recognition criteria is recorded as deferred revenue in the accompanying consolidated balance sheets. Although we follow detailed guidelines in measuring revenue, certain judgments affect the application of our revenue policy. For example, in connection with our existing collaboration agreements, we have recorded on our consolidated balance sheets short-term and long-term deferred revenue based on our best estimate of when such revenue will be recognized. Short-term deferred revenue consists of amounts that are expected to be recognized as revenue in the next 12 months. Amounts that we expect will not be recognized within the next 12 months are classified as long-term deferred revenue. However, this estimate is based on our current operating plan and, if our operating plan should change in the future, we may recognize a different amount of deferred revenue over the next 12-month period. The estimate of deferred revenue also reflects management’s estimate of the periods of our involvement in certain of our collaborations. Our performance obligations under these collaborations consist of participation on steering committees and the performance of other research and development services. In certain instances, the timing of satisfying these obligations can be difficult to estimate. Accordingly, our estimates may change in the future. Such changes to estimates would result in a change in revenue recognition amounts. If these estimates and judgments change over the course of these agreements, it may affect the timing and amount of revenue that we recognize and record in future periods. At December 31, 2018, we had short-term and long-term deferred revenue of $3.5 million and $0.5 million, respectively, all of which was related to our collaboration with Vir.
Cost of Goods Sold	Cost of Goods Sold Cost of goods sold includes the cost of producing and distributing inventories that are related to product revenues during the respective period (including salary-related and stock-based compensation expenses for employees involved with production and distribution, freight and indirect overhead costs), third-party royalties payable on our net product revenues and amortization of intangible assets associated with ONPATTRO. Cost of goods sold may also include costs related to excess or obsolete inventory adjustment charges, abnormal costs, unabsorbed manufacturing and overhead costs, and manufacturing variances.
Other Income	Other Income As described more fully below in Note 9, Dicerna Pharmaceuticals, Inc., or During the fourth quarter of 2018, in connection with the completion of certain business development activities by Dicerna, the $13.0 million cash payment, included in prepaid expenses and other current assets on our consolidated balance sheet, became due and we accreted the remaining discount and recorded $4.0 million in interest income on our consolidated statements of comprehensive loss.
Income Taxes	Income Taxes We use the asset and liability method of accounting for income taxes. Under the asset and liability method, deferred tax assets and liabilities reflect the impact of temporary differences between amounts of assets and liabilities for financial reporting purposes and such amounts as measured under enacted tax laws. A valuation allowance is required to offset any net deferred tax assets if, based upon the available evidence, it is more likely than not that some or all of the deferred tax asset will not be realized. Accounting for income taxes requires a two-step approach to recognize and measure uncertain tax positions. The first step is to evaluate the tax position for recognition by determining if, based on the technical merits, it is more likely than not that the position will be sustained upon audit, including resolution of related appeals or litigation processes, if any. The second step is to measure the tax benefit as the largest amount that is more than 50 percent likely of being realized upon ultimate settlement. We re-evaluate these uncertain tax positions on a quarterly basis. This evaluation is based on factors including, but not limited to, changes in facts or circumstances, changes in tax law, effectively settled issues under audit and new audit activity. Any change in these factors could result in the recognition of a tax benefit or an additional charge to the tax provision. As of December 31, 2018, we have recorded no interest and penalty expense related to uncertain tax positions.
Research and Development Expenses	Research and Development Expenses We record research and development expenses as incurred. Included in research and development expenses are wages, stock-based compensation expenses, benefits and other operating costs, facilities, supplies, external services, clinical trial and manufacturing costs, costs related to our collaboration arrangements and overhead directly related to our research and development operations, as well as costs to acquire technology licenses. We have entered into several license agreements for rights to utilize certain technologies. The terms of the licenses may provide for upfront payments, annual maintenance payments, milestone payments based upon certain specified events being achieved and royalties on product sales. We charge costs to acquire and maintain licensed technology that has not reached technological feasibility and does not have alternative future use to research and development expense as incurred. During the years ended December 31, 2018, 2017 and 2016, we charged to research and development expense costs associated with license fees of $8.0 million, $7.7 million and $2.4 million, respectively.
Stock-Based Compensation	Stock-Based Compensation We have stock incentive plans and an employee stock purchase plan under which we grant equity instruments. We may also grant inducement stock grants outside of our stock incentive plans. We account for all stock-based awards granted to employees at their fair value and generally recognize compensation expense over the vesting period of the award. Determining the amount of stock-based compensation to be recorded requires us to develop estimates of fair values of stock options as of the grant date. We calculate the grant date fair values of stock options using the Black-Scholes valuation model. Our expected stock price volatility assumption is based on the historical volatility of our publicly traded stock. The fair value of restricted stock awards granted to employees is based upon the quoted closing market price per share on the date of grant. Expense for time-based restricted stock awards is recognized over the vesting period. For performance-based stock option and restricted stock awards, we begin to recognize expense when we determine that the achievement of such performance conditions is deemed probable. This determination requires significant judgment by management. At the probable date, we record a cumulative expense catch-up, with remaining expense amortized over the remaining service period.
Comprehensive Loss	Comprehensive Loss Comprehensive loss is comprised of net loss and certain changes in stockholders’ equity that are excluded from net loss. We include foreign currency translation adjustments in other comprehensive loss if the functional currency is not the U.S. dollar. We include unrealized gains and losses on certain marketable securities in other comprehensive loss, including changes in the value of our marketable debt securities
Net Loss Per Common Share	Net Loss Per Common Share We compute basic net loss per common share by dividing net loss by the weighted-average number of common shares outstanding. We compute diluted net loss per common share by dividing net loss by the weighted-average number of common shares and dilutive potential common share equivalents then outstanding. Potential common shares consist of shares issuable upon the exercise of stock options (the proceeds of which are then assumed to have been used to repurchase outstanding shares using the treasury stock method). Because the inclusion of potential common shares would be anti-dilutive for all periods presented, diluted net loss per common share is the same as basic net loss per common share. The following table sets forth for the periods presented the potential common shares (prior to consideration of the treasury stock method) excluded from the calculation of net loss per common share because their inclusion would be anti-dilutive, in thousands: At December 31, 2018 2017 2016 Options to purchase common stock 12,573 11,239 12,270 Unvested restricted common stock 36 149 171 12,609 11,388 12,441
Segment Information	Segment Information We operate in a single reporting segment, the discovery, development and commercialization of RNAi therapeutics. During 2018, all of our net revenues from collaborators were attributed to the U.S. and the majority of our net product revenues were attributed to the U.S. During 2017 and 2016, all of our revenues were attributed to the U.S. and consisted solely of net revenues from collaborators. At December 31, 2018 and 2017, substantially all of our consolidated property, plant and equipment, net was from U.S. operations.
Recent Accounting Pronouncements	Recent Accounting Pronouncements In May 2014, the Financial Accounting Standards Board, or FASB, issued a new revenue recognition standard, which we refer to as the new revenue standard, which amends revenue recognition principles and provides a single, comprehensive set of criteria for revenue recognition within and across all industries. The new revenue standard provides a five-step framework whereby revenue is recognized when control of promised goods or services are transferred to a customer at an amount that reflects the consideration to which the entity expects to be entitled in exchange for those goods or services. The new revenue standard also requires enhanced disclosures pertaining to revenue recognition in both interim and annual periods. In August 2015, the FASB deferred the effective date of the new revenue standard from January 1, 2017 to January 1, 2018. In March 2016, the FASB issued amendments to clarify the implementation standard on principal versus agent considerations. In April 2016, the FASB issued amendments to clarify the standard on accounting for licenses of intellectual property and identifying performance obligations. In May 2016, the FASB issued amendments related to collectibility, non-cash consideration, the presentation of sales and other similar taxes collected from customers and transition. The new revenue standard allows for adoption using a full retrospective method or a modified retrospective method. On January 1, 2018, we adopted the new revenue standard by applying the modified retrospective method to all contracts that were not completed as of January 1, 2018. As a result, while reporting periods beginning on our adoption of the new revenue standard are presented under the new revenue standard, prior period amounts have not been adjusted and continue to be presented under the revenue standard in effect prior to January 1, 2018. For contracts that were modified prior to our adoption of the new revenue standard, we reflected the aggregate effect of all modifications that occurred before the beginning of the earliest period presented when identifying performance obligations and allocating the transaction price in accordance with an available practical expedient. Our implementation approach included performing a detailed review of our collaboration agreements not completed as of the transition date. In addition, we designed internal controls to enable the preparation of financial information and have reached conclusions on key accounting assessments related to the new revenue standard, including our assessment that the impact of accounting for costs incurred to obtain a contract is immaterial. There was no impact to cash from or used in operating, financing or investing activities on our consolidated statement of cash flows as a result of the adoption of the new revenue standard. The following table summarizes the cumulative effect to our consolidated balance sheet upon the adoption of the new revenue standard on January 1, 2018, in thousands: Consolidated Balance Sheet Balance at December 31, 2017 Adjustments Balance at January 1, 2018 Deferred revenue, current portion $ 41,705 $ (34,463 ) $ 7,242 Deferred revenue, net of current portion $ 43,075 $ (33,747 ) $ 9,328 Accumulated deficit $ (2,147,685 ) $ 68,210 $ (2,079,475 ) The adoption of the new revenue standard resulted in a cumulative reduction of $68.2 million of deferred revenue with a corresponding adjustment to the opening balance of accumulated deficit recorded in the first quarter of 2018. This adjustment is due primarily to the application of the new revenue standard to our collaboration agreements with Sanofi Genzyme, MDCO and Kyowa Hakko Kirin Co., Ltd., or A substantial portion of the incremental $68.2 million adjustment is the result of the application of the new revenue standard regarding how entities should measure progress in satisfying performance obligations and the contract’s transaction price. In particular, for Sanofi Genzyme and MDCO, the adoption of the new revenue standard resulted in the recognition of previously deferred revenue of $45.7 million and $4.5 million, respectively, due to the change in the way we measure our performance under each agreement, from a straight-line method to a cost-to-cost input model. As a result, at January 1, 2018, the balance of remaining deferred revenues was $3.5 million and $1.2 million, respectively, related to Sanofi Genzyme and MDCO. In addition, the adoption of the new revenue standard resulted in the recognition of $15.5 million of previously deferred revenue related to our Kyowa Hakko Kirin we had been unable to reasonably estimate our period of performance under the Kyowa Hakko Kirin agreement as we were unable to estimate the timeline of our deliverables related to the fixed-price option granted to Kyowa Hakko Kirin for any additional compounds, an obligation that was bundled with all other deliverables into a single unit of accounting. Under the new revenue standard, two distinct performance obligations were identified. The first distinct performance obligation included a license to our program targeting respiratory syncytial virus, or RSV, infection , related know-how and updates, manufacturing supply services and joint steering committee services. The second distinct performance obligation included the fixed-price option to a future follow-on compound. We allocated all consideration to the first performance obligation because the second performance obligation was deemed to have a de minimis relative selling price due to its low likelihood of occurring, in part due to our discontinuation of our RSV program. Given this fact pattern, because we do not expect to incur any future costs related to our RSV program, we concluded our performance obligations were complete in the period prior to our adoption of the new revenue standard and therefore, there would not be a future significant reversal of revenue. As a result, we recorded the $15.5 million of deferred revenue as of December 31, 2017 as an adjustment to the opening balance of our accumulated deficit on January 1, 2018 In accordance with the new revenue standard requirements, the following tables summarize the impact of adoption on our consolidated balance sheet and consolidated statement of comprehensive loss, in thousands: At December 31, 2018 Consolidated Balance Sheet As Reported Balances Without Adoption of New Revenue Standard Effect of Change Higher/(Lower) Deferred revenue, current portion $ 3,496 $ 3,496 $ — Deferred revenue, net of current portion $ 458 $ 18,451 $ (17,993 ) Accumulated deficit $ (2,840,972 ) $ (2,859,049 ) $ (18,077 ) Year Ended December 31, 2018 Consolidated Statement of Comprehensive Loss As Reported Balances Without Adoption of New Revenue Standard Effect of Change Higher/(Lower) Net revenues from collaborators $ 62,373 $ 112,506 $ (50,133 ) Net loss $ (761,497 ) $ (711,364 ) $ 50,133 Net loss per common share - basic and diluted $ (7.57 ) $ (7.07 ) $ 0.50 The impact of our adoption of the new revenue standard did not have a material impact on the amount of net product revenues recognized during the year ended December 31, 2018 . In January 2016, the FASB issued a new standard on recognition and measurement of financial assets and financial liabilities. The new standard impacts the accounting for equity investments, financial liabilities under the fair value option, and the presentation and disclosure requirements for financial instruments. All equity investments in unconsolidated entities (other than those accounted for under the equity method of accounting) will generally be measured at fair value with changes in fair value recognized through earnings. There is no longer an available-for-sale classification (changes in fair value reported in other comprehensive income (loss)) for equity securities with readily determinable fair values. For equity investments that do not have readily determinable fair values, such as privately issued corporate equity securities, we have elected the measurement alternative. As a result, we will record these investments at cost, less any impairment, and adjust for observable price changes in orderly transactions for identical or similar investments of the same issuer. At December 31, 2018 and December 31, 2017, we did not have material equity investments without readily determinable fair values. In addition, the FASB clarified the need for a valuation allowance on deferred tax assets resulting from unrealized losses on available-for-sale debt securities. In general, the new standard requires modified retrospective application to all outstanding instruments, with a cumulative effect adjustment recorded to opening retained earnings. This standard became effective for us on January 1, 2018. This standard did not have a significant impact on our consolidated financial statements and related disclosures. In February 2016, the FASB issued a new leasing standard which generally requires lessees to recognize operating and financing lease liabilities and corresponding right-of-use assets on the consolidated balance sheet and to provide enhanced disclosures surrounding the amount, timing and uncertainty of cash flows arising from leasing arrangements. We adopted the new standard on January 1, 2019, using a modified retrospective basis and will not restate comparative periods. Presentation of leases within the consolidated statements of comprehensive loss and consolidated statements of cash flows will be generally consistent with the current lease accounting guidance. We did not elect the package of practical expedients permitted under the transition guidance, however the adoption of the new standard will not change the classification of any of our leases. We elected to combine lease and non-lease components and to keep leases with an initial term of 12 months or less off the consolidated balance sheet and recognize the associated lease payments in the consolidated statements comprehensive loss on a straight-line basis over the lease term. We expect to recognize approximately $290 million as total lease liabilities and approximately $230 million as total right-of-use assets on our consolidated balance sheet as of January 1, 2019. The adoption of this standard is not expected to have a significant impact on our consolidated statements of comprehensive loss and consolidated statements of cash flows. In November 2016, the FASB issued a new standard that requires restricted cash and restricted cash equivalents be included with cash and cash equivalents when reconciling the total beginning and ending amounts for the periods shown on the consolidated statements of cash flows. The new standard became effective for us on January 1, 2018 using a retrospective transition method for each period presented. For the years ended December 31, 2017 and 2016, our restricted cash and restricted cash equivalents were not significant. This standard did not have a significant impact on our consolidated financial statements and related disclosures. In March 2017, the FASB issued a new standard that amends the amortization period for certain purchased callable debt securities held at a premium by shortening the amortization period for the premium to the earliest call date. The new standard became effective for us on January 1, 2019. This standard did not have a significant impact on our consolidated financial statements and related disclosures. In March 2018, the FASB issued a new standard to incorporate the U.S. Securities and Exchange Commission, or SEC, Staff Accounting Bulletin No. 118, or SAB 118, which addresses the accounting implications of the Tax Cuts and Jobs Act In June 2018, the FASB issued amendments to simplify the accounting for share-based payment awards to nonemployees by aligning the measurement and classification guidance, with certain exceptions, to that for share-based payment awards to employees. The amendments expand the scope of the accounting standard for share-based payment awards to include share-based payment awards granted to non-employees in exchange for goods or services used or consumed in an entity’s own operations and supersedes the guidance related to equity-based payments to non-employees. We elected to early adopt these amendments on July 1, 2018. The adoption of these amendments did not have a significant impact on our consolidated financial statements and related disclosures. In August 2018, the FASB issued amendments that eliminate, add and modify certain disclosure requirements on fair value measurements. The amendments become effective for our fiscal year, including interim periods, beginning January 1, 2020. Early adoption of the amendments, in full or only the provisions that eliminate or modify the disclosure requirements for fair value measurements is permitted. We are currently evaluating the timing of our adoption and the expected impact that these amendments could have on our disclosures In August 2018, the SEC issued a final rule amending certain disclosure requirements that were redundant, duplicative, overlapping, outdated or superseded. In addition, the amendments expanded the disclosure requirements on the analysis of stockholders’ equity for interim financial statements. Under the amendments, an analysis of changes in each caption of stockholders' equity presented in the consolidated balance sheet must be provided in a note or separate statement. This analysis should present a reconciliation of the beginning balance to the ending balance of each caption in stockholders’ equity for each period for which a consolidated statement of comprehensive loss is required to be filed. This final rule became effective on November 5, 2018. However, the SEC issued guidance that they will not object if a company initially presents the changes in stockholders’ equity in its first quarterly report for the quarter that begins after the effective date of the final rule. Our adoption of the final rule resulted in the removal of certain duplicative and/or outdated disclosures in this annual report on Form 10-K. In November 2018, the FASB issued guidance to clarify the interaction between the accounting guidance for collaborative arrangements and revenue from contracts with customers. The amendments become effective for our fiscal year, including interim periods, beginning January 1, 2020. Early adoption, including adoption in any interim period, is permitted. This guidance is required to be applied retrospectively as of the date of our adoption of the new revenue standard on January 1, 2018. We are currently evaluating the timing of our adoption and the expected impact this guidance could have on our consolidated financial statements and related disclosures
Subsequent Events	Subsequent Events We did not have any material recognized subsequent events. However, we did have the following nonrecognized subsequent event, which is more fully described in Note 10. • In January 2019, we sold an aggregate of 5,000,000 shares of our common stock through an underwritten public offering at a price to the public of $77.50 per share.

SUMMARY OF SIGNIFICANT ACCOUN_3

SUMMARY OF SIGNIFICANT ACCOUNTING POLICIES (Tables)	12 Months Ended
	Dec. 31, 2018
Accounting Policies [Abstract]
Concentrations of Credit Risk and Significant Customers	The following table summarizes customers that represent greater than 10 percent of our consolidated total gross revenues for the periods indicated: Year Ended December 31, 2018 2017 2016 Sanofi Genzyme 58 % 61 % 68 % Vir Biotechnology 16 % * N/A Distributor A 13 % N/A N/A MDCO * 34 % 24 % * Represents 10 percent or less The following table summarizes customers with amounts due that represent greater than 10 percent of our gross accounts receivable balance, at the periods indicated: At December 31, 2018 2017 Distributor A 44 % N/A Sanofi Genzyme 29 % 39 % MDCO * 59 % * Represents 10 percent or less
Estimated Useful Lives of Property, Plant and Equipment	The estimated useful lives of property, plant and equipment are as follows: Asset Category Useful Life Laboratory equipment 5 years Computer equipment and software 3-10 years Furniture and fixtures 5 years Leasehold improvements Shorter of asset life or lease term Land — Construction in progress —
Common Shares Excluded from the Calculation of Net Loss Per Common Share	The following table sets forth for the periods presented the potential common shares (prior to consideration of the treasury stock method) excluded from the calculation of net loss per common share because their inclusion would be anti-dilutive, in thousands: At December 31, 2018 2017 2016 Options to purchase common stock 12,573 11,239 12,270 Unvested restricted common stock 36 149 171 12,609 11,388 12,441
Cumulative Effect and Impact on Consolidated Balance Sheet and Consolidated Statement of Comprehensive Loss for Adoption of New Revenue Standard	The following table summarizes the cumulative effect to our consolidated balance sheet upon the adoption of the new revenue standard on January 1, 2018, in thousands: Consolidated Balance Sheet Balance at December 31, 2017 Adjustments Balance at January 1, 2018 Deferred revenue, current portion $ 41,705 $ (34,463 ) $ 7,242 Deferred revenue, net of current portion $ 43,075 $ (33,747 ) $ 9,328 Accumulated deficit $ (2,147,685 ) $ 68,210 $ (2,079,475 ) In accordance with the new revenue standard requirements, the following tables summarize the impact of adoption on our consolidated balance sheet and consolidated statement of comprehensive loss, in thousands: At December 31, 2018 Consolidated Balance Sheet As Reported Balances Without Adoption of New Revenue Standard Effect of Change Higher/(Lower) Deferred revenue, current portion $ 3,496 $ 3,496 $ — Deferred revenue, net of current portion $ 458 $ 18,451 $ (17,993 ) Accumulated deficit $ (2,840,972 ) $ (2,859,049 ) $ (18,077 ) Year Ended December 31, 2018 Consolidated Statement of Comprehensive Loss As Reported Balances Without Adoption of New Revenue Standard Effect of Change Higher/(Lower) Net revenues from collaborators $ 62,373 $ 112,506 $ (50,133 ) Net loss $ (761,497 ) $ (711,364 ) $ 50,133 Net loss per common share - basic and diluted $ (7.57 ) $ (7.07 ) $ 0.50

PRODUCT REVENUES, NET (Tables)

PRODUCT REVENUES, NET (Tables)	12 Months Ended
	Dec. 31, 2018
Revenue From Contract With Customer [Abstract]
Summary of Balances and Activity in Each Product Revenue Allowance and Reserve Category	The following table summarizes balances and activity in each product revenue allowance and reserve category during the year ended December 31, 2018, in thousands, related to sales of ONPATTRO subsequent to its approval by the FDA and EC in August 2018: Chargebacks Rebates Trade Discounts and Allowances Returns Reserve Other Incentives Total Beginning balance $ — $ — $ — $ — $ — $ — Provision related to current period sales 1,553 2,528 292 106 551 5,030 Credit or payments made during the period (640 ) — (74 ) — (336 ) (1,050 ) Total $ 913 $ 2,528 $ 218 $ 106 $ 215 $ 3,980

SIGNIFICANT AGREEMENTS (Tables)

SIGNIFICANT AGREEMENTS (Tables)	12 Months Ended
	Dec. 31, 2018
Revenue from Collaborators	The following table summarizes our total consolidated net revenues from collaborators, for the periods indicated, in thousands: Year Ended December 31, Description 2018 2017 2016 Sanofi Genzyme $ 46,000 $ 54,625 $ 32,015 Vir Biotechnology 12,778 1,464 — MDCO 2,789 30,217 11,220 Other 806 3,606 3,924 Total net revenues from collaborators $ 62,373 $ 89,912 $ 47,159
Balance and Change in Contract Liabilities Related to Collaboration Agreements	The following table presents the balance of our contract liabilities related to our collaboration agreements at December 31, 2018 and January 1, 2018, in thousands: At December 31, 2018 At January 1, 2018 Contract liabilities: Deferred revenues $ 3,954 $ 16,570 During the year ended December 31, 2018, we recognized the following revenues as a result of the change in the contract liability balances related to our collaboration agreements, in thousands: Revenue recognized in the period from: Year Ended December 31, 2018 Amounts included in contract liability at the beginning of the period $ 16,570
Schedule of Research and Development Expenses Incurred by Type that are Directly Attributable to Collaboration Agreements	The following table provides the research and development expenses incurred by type that are directly attributable to our collaboration agreements by collaboration partner for the periods indicated, in thousands: Year Ended December 31, 2018 2017 2016 Sanofi Genzyme Vir MDCO Ionis Sanofi Genzyme Vir MDCO Ionis Sanofi Genzyme Vir MDCO Ionis Research and development Clinical trial and manufacturing $ 36,600 $ 7,272 $ 1,664 $ — $ 174,901 $ 1,134 $ 5,421 $ — $ 150,179 $ — $ 1,211 $ — External services 5,340 8,251 2 2,150 4,475 926 — 3,250 7,366 — — — Other 1,279 548 203 1,097 5,327 — 106 — 3,035 — 64 525 Total research and development expenses $ 43,219 $ 16,071 $ 1,869 $ 3,247 $ 184,703 $ 2,060 $ 5,527 $ 3,250 $ 160,580 $ — $ 1,275 $ 525
Prior Revenue Standard | ASU 2014-09 Revenue from Contracts with Customers
Revenue from Collaborators	The following table summarizes our total consolidated net revenues from collaborators, using the prior revenue standard, for the periods indicated, in thousands: Year Ended December 31, Description 2018 2017 2016 Sanofi Genzyme $ 91,738 $ 54,625 $ 32,015 Vir Biotechnology 12,778 1,464 — MDCO 7,184 30,217 11,220 Other 806 3,606 3,924 Total net revenues from collaborators $ 112,506 $ 89,912 $ 47,159

INVENTORY (Tables)

INVENTORY (Tables)	12 Months Ended
	Dec. 31, 2018
Inventory Disclosure [Abstract]
Schedule of Inventory	The following table presents our inventory of ONPATTRO at December 31, 2018 and 2017, in thousands: At December 31, 2018 2017 Raw materials $ 8,709 $ — Work in process 15,262 — Finished goods 97 — Total inventory $ 24,068 $ —

FAIR VALUE MEASUREMENTS (Tables

FAIR VALUE MEASUREMENTS (Tables)	12 Months Ended
	Dec. 31, 2018
Fair Value Disclosures [Abstract]
Fair Value of Assets Measured on a Recurring Basis	The following tables present information about our assets that are measured at fair value on a recurring basis at December 31, 2018 and 2017, and indicate the fair value hierarchy of the valuation techniques we utilized to determine such fair value, in thousands: Description At December 31, 2018 Quoted Prices in Active Markets (Level 1) Significant Observable Inputs (Level 2) Significant Unobservable Inputs (Level 3) Cash equivalents: U.S. treasury securities $ 221,281 $ — $ 221,281 $ — Money market funds 102,445 102,445 — — Marketable debt securities: — Certificates of deposit 8,951 — 8,951 — Commercial paper 57,197 — 57,197 — Corporate notes 232,410 — 232,410 — U.S. government-sponsored enterprise securities 39,018 — 39,018 — U.S. treasury securities 325,227 — 325,227 — Marketable equity securities 1,206 1,206 — Restricted cash (money market funds) 1,477 1,477 — — Total $ 989,212 $ 105,128 $ 884,084 $ — Description At December 31, 2017 Quoted Prices in Active Markets (Level 1) Significant Observable Inputs (Level 2) Significant Unobservable Inputs (Level 3) Cash equivalents: Commercial paper $ 82,262 $ — $ 82,262 $ — Corporate notes 18,116 — 18,116 — U.S. government-sponsored enterprise securities 231,122 — 231,122 — U.S. treasury securities 62,855 — 62,855 — Money market funds 122,986 122,986 — — Marketable debt securities: — Certificates of deposit 30,200 — 30,200 — Commercial paper 56,951 — 56,951 — Corporate notes 373,252 — 373,252 — U.S. government-sponsored enterprise securities 398,298 — 398,298 — U.S. treasury securities 200,475 — 200,475 — Restricted cash (money market funds) 1,471 1,471 — — Total $ 1,577,988 $ 124,457 $ 1,453,531 $ —

MARKETABLE DEBT SECURITIES (Tab

MARKETABLE DEBT SECURITIES (Tables)	12 Months Ended
	Dec. 31, 2018
Investments Debt And Equity Securities [Abstract]
Summary of Company's Marketable Debt Securities	The following tables summarize our marketable debt securities at December 31, 2018 and 2017, in thousands: At December 31, 2018 Amortized Cost Gross Unrealized Gains Gross Unrealized Losses Fair Value Certificates of deposit $ 8,951 $ — $ — $ 8,951 Commercial paper 57,197 — — 57,197 Corporate notes 232,695 — (285 ) 232,410 U.S. government-sponsored enterprise securities 39,031 — (13 ) 39,018 U.S. treasury securities 325,350 1 (124 ) 325,227 Total $ 663,224 $ 1 $ (422 ) $ 662,803 At December 31, 2017 Amortized Cost Gross Unrealized Gains Gross Unrealized Losses Fair Value Certificates of deposit $ 30,200 $ — $ — $ 30,200 Commercial paper 56,951 — — 56,951 Corporate notes 373,736 11 (495 ) 373,252 U.S. government-sponsored enterprise securities 399,281 — (983 ) 398,298 U.S. treasury securities 200,649 1 (175 ) 200,475 Total $ 1,060,817 $ 12 $ (1,653 ) $ 1,059,176
Summary of Available-For-Sale Debt Securities by Contractual Maturity	The following table summarizes our available-for-sale debt securities by contractual maturity, at December 31, 2018, in thousands: At December 31, 2018 Amortized Cost Fair Value Less than one year $ 663,224 $ 662,803 Greater than one year but less than five years — — Total $ 663,224 $ 662,803

PROPERTY, PLANT AND EQUIPMENT_2

PROPERTY, PLANT AND EQUIPMENT, NET (Tables)	12 Months Ended
	Dec. 31, 2018
Property Plant And Equipment [Abstract]
Property, Plant and Equipment, Net	Property, plant and equipment, net consist of the following at December 31, 2018 and 2017, in thousands: At December 31, 2018 2017 Laboratory equipment $ 43,427 $ 40,462 Computer equipment and software 13,495 9,608 Furniture and fixtures 7,238 5,844 Leasehold improvements 65,928 50,612 Land 9,080 9,080 Construction in progress 260,975 133,645 400,143 249,251 Less: accumulated depreciation (79,485 ) (67,351 ) $ 320,658 $ 181,900

COMMITMENTS AND CONTINGENCIES (

COMMITMENTS AND CONTINGENCIES (Tables)	12 Months Ended
	Dec. 31, 2018
Commitments And Contingencies Disclosure [Abstract]
Fixed and Cancelable Payments under Existing License and Other Technology Agreements	At December 31, 2018, we expect to make the following fixed and cancelable payments under existing license agreements, in thousands: Year Ending December 31, 2019 $ 1,453 2020 795 2021 745 2022 545 2023 525 Thereafter 525 Total $ 4,588
Future Minimum Payments Under Non-cancelable Leases	Future minimum payments under our non-cancelable facility leases, including rent payments for the BMR-675 West Kendall Lease which commenced in February 2019, are approximately as follows, in thousands: Year Ending December 31, 2019 $ 32,228 2020 34,826 2021 34,410 2022 34,826 2023 35,270 Thereafter 390,455 Total $ 562,015

STOCK-BASED COMPENSATION (Table

STOCK-BASED COMPENSATION (Tables)	12 Months Ended
	Dec. 31, 2018
Summary of Stock-Based Compensation Expense	The following table summarizes stock-based compensation expense during the three years ended December 31, 2018, in thousands: 2018 2017 2016 Stock-based compensation expense by type of award: Time-based stock options $ 83,403 $ 61,802 $ 62,800 Performance-based stock options 56,419 23,260 8,337 Time-based restricted stock units 538 541 497 Performance-based restricted stock units 13,144 — — ESPP share issuances 2,842 2,155 1,360 Other equity programs 1,345 1,946 1,846 Non-employee stock options 1,485 3,115 688 Less: Stock-based compensation expense capitalized to inventory (1,424 ) — — $ 157,752 $ 92,819 $ 75,528
Summary of Unrecognized Stock-Based Compensation Expense, Net of Estimated Forfeitures	The following table summarizes our unrecognized stock-based compensation expense, net of estimated forfeitures, at December 31, 2018 by type of awards, and the weighted-average period over which that expense is expected to be recognized: At December 31, 2018 Unrecognized Expense, Net of Estimated Forfeitures Weighted- average Recognition Period (in thousands) (in years) Type of award: Time-based stock options $ 156,192 2.53 Performance-based stock options 57,586 * Time-based restricted stock units 769 0.78 Performance-based restricted stock units 1,747 * ESPP share issuances 984 0.33 * Performance-based stock options and performance-based restricted stock units are recorded as expense beginning when vesting events are determined to be probable.
Valuation Assumptions for Stock Options	2018 2017 2016 Risk-free interest rate 2.7-2.9% 1.9-2.3% 0.9-2.2% Expected dividend yield — — — Expected option life 5.7-7.2 years 5.7-7.2 years 3.5-7.5 years Expected volatility 64-67% 61-67% 55-65%
Stock Option and Inducement Grant Activity	The following table summarizes the activity of our stock option plans and the inducement grants described above, excluding performance-based stock options: Number of Options (in Weighted- average Exercise Price Weighted- average Remaining Contractual Term (in years) Aggregate Intrinsic Value (in thousands) Outstanding, December 31, 2017 9,101 $ 60.18 Granted 2,273 110.11 Exercised (1,181 ) 46.92 Cancelled (364 ) 82.89 Outstanding, December 31, 2018 9,829 $ 72.48 6.68 $ 149,518 Exercisable at December 31, 2018 5,734 $ 58.90 5.31 $ 127,051 Vested or expected to vest at December 31, 2018 9,327 $ 71.36 6.56 $ 147,144
Performance-based stock options
Stock Option and Inducement Grant Activity	The following table summarizes the activity of our performance-based stock options granted under our equity plans and the performance-based portion of the inducement grants described above: Number of Options (in Weighted- average Exercise Price Weighted- average Remaining Contractual Term (in years) Aggregate Intrinsic Value (in thousands) Outstanding, December 31, 2017 2,138 $ 69.14 Granted 912 119.13 Exercised (149 ) 67.04 Cancelled (157 ) 88.64 Outstanding, December 31, 2018 2,744 $ 84.75 7.24 $ 23,694 Exercisable at December 31, 2018 1,420 $ 74.29 6.21 $ 13,134

INCOME TAXES (Tables)

INCOME TAXES (Tables)	12 Months Ended
	Dec. 31, 2018
Income Tax Disclosure [Abstract]
Schedule of Domestic and Foreign Components of Loss before Income Taxes	The domestic and foreign components of loss before income taxes are as follows, in thousands: 2018 2017 2016 Domestic $ (573,245 ) $ (378,293 ) $ (350,704 ) Foreign (187,429 ) (112,581 ) (59,404 ) Loss before income taxes $ (760,674 ) $ (490,874 ) $ (410,108 )
Schedule of Provision for Income Taxes	The provision for income taxes for each of the years ended December 31, 2018, 2017 and 2016 consisted of the following: 2018 2017 2016 Current provision: Domestic $ — $ — $ — Foreign (1,611 ) — — Total current provision (1,611 ) — — Deferred benefit: Federal 788 — — Foreign — — — Total deferred benefit 788 — — Total provision for income taxes $ (823 ) $ — $ —
Schedule of Components of Net Deferred Tax (Liability) Asset	Components of the net deferred tax (liability) asset at December 31, 2018 and 2017 are as follows, in thousands: 2018 2017 Deferred tax assets: Net operating loss carryforwards $ 506,574 $ 405,784 Research and development and ODC credits 220,776 192,094 AMT credits 788 788 Capitalized research and development and start-up costs 12,139 13,163 Deferred revenue — 13,576 Deferred compensation 57,268 42,990 Property, plant and equipment, net — 2,471 Intangible assets 50,121 9,018 Other 20,660 9,137 Total deferred tax assets 868,326 689,021 Deferred tax liabilities: Property, plant and equipment, net (6,550 ) — Unrealized gain on marketable securities (903 ) (765 ) Deferred tax asset valuation allowance (860,085 ) (688,256 ) Net deferred tax asset $ 788 $ —
Schedule of Effective Income Tax Rate Differs from Statutory Federal Income Tax Rate	Our effective income tax rate differs from the statutory federal income tax rate as follows for the years ended December 31, 2018, 2017 and 2016: 2018 2017 2016 At U.S. federal statutory rate 21.0 % 35.0 % 35.0 % State taxes, net of federal effect 2.1 3.8 3.7 Stock-based compensation 0.8 3.3 (1.4 ) Tax credits 4.2 9.9 11.8 Orphan drug credit — (3.4 ) (3.5 ) Other permanent items (0.3 ) (1.0 ) (0.4 ) Foreign rate differential (5.3 ) (8.1 ) (5.1 ) Tax reform change — (46.5 ) — Revaluation of deferred credits due to rate change (3.5 ) — — Other — (0.9 ) — Valuation allowance (19.0 ) 7.9 (40.1 ) Effective income tax rate — % — % — %

ACCRUED EXPENSES (Tables)

ACCRUED EXPENSES (Tables)	12 Months Ended
	Dec. 31, 2018
Accrued Liabilities Current [Abstract]
Accrued Expenses	Accrued expenses consist of the following at December 31, 2018 and 2017, in thousands: At December 31, 2018 2017 Compensation and related $ 37,301 $ 33,826 Clinical trial and manufacturing 36,500 20,004 Consulting and professional services 10,450 7,276 Product revenue allowances 2,696 — Pre-clinical 2,138 239 Other 23,634 10,858 $ 112,719 $ 72,203

QUARTERLY FINANCIAL DATA (UNA_2

QUARTERLY FINANCIAL DATA (UNAUDITED) (Tables)	12 Months Ended
	Dec. 31, 2018
Quarterly Financial Information Disclosure [Abstract]
Schedule of Quarterly Financial Information	The following information has been derived from unaudited consolidated financial statements that, in the opinion of management, include all recurring adjustments necessary for a fair statement of such information. Three Months Ended March 31, 2018 June 30, 2018 September 30, 2018 December 31, 2018 (In thousands, except per share data) Revenues $ 21,899 $ 29,907 $ 2,069 $ 21,033 Operating costs and expenses 169,304 222,261 256,627 241,389 Net loss $ (141,214 ) $ (163,560 ) $ (245,282 ) $ (211,441 ) Net loss per common share — basic and diluted $ (1.41 ) $ (1.63 ) $ (2.43 ) $ (2.09 ) Weighted-average common shares — basic and diluted 99,979 100,519 100,783 101,066 Three Months Ended March 31, 2017 June 30, 2017 September 30, 2017 December 31, 2017 (In thousands, except per share data) Revenues $ 18,960 $ 15,932 $ 17,096 $ 37,924 Operating costs and expenses 125,471 136,406 142,896 185,227 Net loss $ (107,290 ) $ (118,420 ) $ (122,937 ) $ (142,227 ) Net loss per common share — basic and diluted $ (1.25 ) $ (1.34 ) $ (1.34 ) $ (1.48 ) Weighted-average common shares — basic and diluted 86,027 88,098 91,828 96,139

Customers that Represent Greate

Customers that Represent Greater than Ten Percent of Gross Revenues (Detail) - Revenue from Rights Concentration Risk - Gross Revenues	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Sanofi Genzyme
Concentration Risk [Line Items]
Concentration risk percentage	58.00%	61.00%	68.00%
Vir Biotechnology
Concentration Risk [Line Items]
Concentration risk percentage	16.00%
MDCO
Concentration Risk [Line Items]
Concentration risk percentage		34.00%	24.00%
Distributor A
Concentration Risk [Line Items]
Concentration risk percentage	13.00%

Customers that Represent Grea_2

Customers that Represent Greater than Ten Percent of Gross Accounts Receivable (Detail) - Accounts Receivable - Credit Concentration Risk	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017
Distributor A
Concentration Risk [Line Items]
Concentration risk percentage	44.00%
MDCO
Concentration Risk [Line Items]
Concentration risk percentage		59.00%
Sanofi Genzyme
Concentration Risk [Line Items]
Concentration risk percentage	29.00%	39.00%

Summary of Significant Accoun_4

Summary of Significant Accounting Policies - Investments in Marketable Securities and Cash Equivalents - Additional Information (Detail) - USD ($)	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Significant Accounting Policies [Line Items]
Gains or losses from sale of available-for-sale debt securities	$ 0	$ 0	$ 0
Reclassification from AOCI for Available for sale debt securities	$ 0	0	0
Marketable securities classified as cash equivalents, maximum original maturity	90 days
Policy for marketable securities	90 days
Realized gain (loss) on sale of marketable equity securities		(1,894,000)	6,977,000
Accumulated other comprehensive loss, net of tax	$ 33,213,000	34,433,000
Regulus Therapeutics Inc
Significant Accounting Policies [Line Items]
Realized gain (loss) on sale of marketable equity securities		(1,900,000)	$ 7,000,000
Accumulated other comprehensive loss, net of tax	$ 32,800,000	$ 32,800,000

Summary of Significant Accoun_5

Summary of Significant Accounting Policies - Accounts Receivable - Additional Information (Detail)	12 Months Ended
	Dec. 31, 2018
Minimum
Significant Accounting Policies [Line Items]
Accounts receivable payment term	30 days
Maximum
Significant Accounting Policies [Line Items]
Accounts receivable payment term	50 days

Summary of Significant Accoun_6

Summary of Significant Accounting Policies - Inventory - Additional Information (Detail)	12 Months Ended
	Dec. 31, 2018USD ($)
Inventory Disclosure [Abstract]
Impairment of capitalized inventory	$ 0

Estimated Useful Lives of Prope

Estimated Useful Lives of Property, Plant and Equipment (Detail)	12 Months Ended
	Dec. 31, 2018
Laboratory equipment
Property, Plant and Equipment [Line Items]
Property, plant and equipment, useful life	5 years
Computer equipment and software | Minimum
Property, Plant and Equipment [Line Items]
Property, plant and equipment, useful life	3 years
Computer equipment and software | Maximum
Property, Plant and Equipment [Line Items]
Property, plant and equipment, useful life	10 years
Furniture and Fixtures
Property, Plant and Equipment [Line Items]
Property, plant and equipment, useful life	5 years
Leasehold improvements
Property, Plant and Equipment [Line Items]
Property, plant and equipment, useful life	Shorter of asset life or lease term

Summary of Significant Accoun_7

Summary of Significant Accounting Policies - Revenue Recognition - Additional Information (Detail)	Dec. 31, 2018USD ($)
Revenue From Contract With Customer [Abstract]
Capitalized cost	$ 0

Summary of Significant Accoun_8

Summary of Significant Accounting Policies - Product revenues, net - Additional Information (Detail)	12 Months Ended
	Dec. 31, 2018
Accounting Policies [Abstract]
Product returns, description	ONPATTRO may be returned if it is damaged, defective or expired, with “expired” defined as having three months or less to expiry or within three months past expiry.

Summary of Significant Accoun_9

Summary of Significant Accounting Policies - Revenues from Collaborators - Additional Information (Detail) - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
Significant Accounting Policies [Line Items]
Deferred revenue, current portion	$ 3,496	$ 41,705
Deferred revenue, net of current portion	458	$ 43,075
Vir
Significant Accounting Policies [Line Items]
Deferred revenue, current portion	3,500
Deferred revenue, net of current portion	$ 500

Summary of Significant Accou_10

Summary of Significant Accounting Policies - Other Income - Additional Information (Detail) - USD ($) $ in Thousands	Apr. 18, 2018	Dec. 31, 2018	Jun. 30, 2018	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Significant Accounting Policies [Line Items]
Gain on litigation settlement				$ 20,564
Interest income				$ 29,262	$ 12,236	$ 8,308
Dicerna Pharmaceuticals, Inc
Significant Accounting Policies [Line Items]
Gain on litigation settlement			$ 20,600
Valuation at settlement date of common stock received from litigation settlement	$ 10,000
Upfront cash payment	2,000
Litigation settlement discounted present value of additional payment	8,600
Additional payment due from litigation settlement	$ 13,000
Interest income		$ 4,000
Litigation settlement agreement payment due date for additional payment	Apr. 18, 2022

Summary of Significant Accou_11

Summary of Significant Accounting Policies - Income Taxes - Additional Information (Detail) - USD ($)	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Income Tax Disclosure [Abstract]
Interest and penalty expense related to uncertain tax positions	$ 0	$ 0	$ 0

Summary of Significant Accou_12

Summary of Significant Accounting Policies - Research and Development Expenses - Additional Information (Detail) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Research and Development
Significant Accounting Policies [Line Items]
Research and development expense costs associated with license fees	$ 8	$ 7.7	$ 2.4

Potential Common Shares Exclude

Potential Common Shares Excluded from Calculation of Net Loss Per Common Share (Detail) - shares shares in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Antidilutive Securities Excluded from Computation of Earnings Per Share [Line Items]
Anti-dilutive securities excluded from computation of earnings per share	12,609	11,388	12,441
Options to purchase common stock
Antidilutive Securities Excluded from Computation of Earnings Per Share [Line Items]
Anti-dilutive securities excluded from computation of earnings per share	12,573	11,239	12,270
Unvested restricted common stock
Antidilutive Securities Excluded from Computation of Earnings Per Share [Line Items]
Anti-dilutive securities excluded from computation of earnings per share	36	149	171

Summary of Significant Accou_13

Summary of Significant Accounting Policies - Segment - Additional Information (Detail)	12 Months Ended
	Dec. 31, 2018Segment
Segment Reporting [Abstract]
Number of reporting segment	1

Cumulative Effect to Consolidat

Cumulative Effect to Consolidated Balance Sheet for Adoption of New Revenue Standard (Detail) - USD ($) $ in Thousands	Dec. 31, 2018	Jan. 01, 2018	Dec. 31, 2017
Revenue Initial Application Period Cumulative Effect Transition [Line Items]
Deferred revenue, current portion	$ 3,496		$ 41,705
Deferred revenue, net of current portion	458		43,075
Accumulated deficit	(2,840,972)		$ (2,147,685)
ASU 2014-09 Revenue from Contracts with Customers
Revenue Initial Application Period Cumulative Effect Transition [Line Items]
Deferred revenue, current portion		$ 7,242
Deferred revenue, net of current portion		9,328
Accumulated deficit		(2,079,475)
ASU 2014-09 Revenue from Contracts with Customers | Effect of Change Higher/(Lower)
Revenue Initial Application Period Cumulative Effect Transition [Line Items]
Deferred revenue, current portion		(34,463)
Deferred revenue, net of current portion	(17,993)	(33,747)
Accumulated deficit	$ (18,077)	$ 68,210

Summary of Significant Accou_14

Summary of Significant Accounting Policies - Recent Accounting Pronouncements - Additional Information (Detail) - USD ($) $ in Thousands	Jan. 01, 2018	Dec. 31, 2018	Jan. 01, 2019
Significant Accounting Policies [Line Items]
Recognition of deferred revenue		$ 16,570
Accounting Standards Update 2016-02 | Subsequent Event
Significant Accounting Policies [Line Items]
Lease liabilities			$ 290,000
Right-of-use assets			$ 230,000
ASU 2014-09 Revenue from Contracts with Customers | Sanofi Genzyme
Significant Accounting Policies [Line Items]
Recognition of deferred revenue	$ 45,700
Remaining deferred revenues	3,500
ASU 2014-09 Revenue from Contracts with Customers | MDCO
Significant Accounting Policies [Line Items]
Recognition of deferred revenue	4,500
Remaining deferred revenues	1,200
ASU 2014-09 Revenue from Contracts with Customers | Kyowa Hakko Kirin
Significant Accounting Policies [Line Items]
Recognition of deferred revenue	15,500
ASU 2014-09 Revenue from Contracts with Customers | Reduction In Deferred Revenue
Significant Accounting Policies [Line Items]
Offsetting adjustments to accumulated deficit	(68,200)
ASU 2014-09 Revenue from Contracts with Customers | Reduction In Deferred Tax Asset
Significant Accounting Policies [Line Items]
Offsetting adjustments to accumulated deficit	$ (13,600)

Impact on Consolidated Balance

Impact on Consolidated Balance Sheet and Consolidated Statement of Comprehensive Loss for Adoption of New Revenue Standard (Detail) - USD ($) $ / shares in Units, $ in Thousands	3 Months Ended								12 Months Ended
	Dec. 31, 2018	Sep. 30, 2018	Jun. 30, 2018	Mar. 31, 2018	Dec. 31, 2017	Sep. 30, 2017	Jun. 30, 2017	Mar. 31, 2017	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016	Jan. 01, 2018
Revenue Initial Application Period Cumulative Effect Transition [Line Items]
Deferred revenue, current portion	$ 3,496				$ 41,705				$ 3,496	$ 41,705
Deferred revenue, net of current portion	458				43,075				458	43,075
Accumulated deficit	(2,840,972)				(2,147,685)				(2,840,972)	(2,147,685)
Revenues	21,033	$ 2,069	$ 29,907	$ 21,899	37,924	$ 17,096	$ 15,932	$ 18,960	74,908	89,912	$ 47,159
Net loss	$ (211,441)	$ (245,282)	$ (163,560)	$ (141,214)	$ (142,227)	$ (122,937)	$ (118,420)	$ (107,290)	$ (761,497)	$ (490,874)	$ (410,108)
Net loss per common share — basic and diluted	$ (2.09)	$ (2.43)	$ (1.63)	$ (1.41)	$ (1.48)	$ (1.34)	$ (1.34)	$ (1.25)	$ (7.57)	$ (5.42)	$ (4.79)
Net Revenues from Collaborators
Revenue Initial Application Period Cumulative Effect Transition [Line Items]
Revenues									$ 62,373	$ 89,912	$ 47,159
ASU 2014-09 Revenue from Contracts with Customers
Revenue Initial Application Period Cumulative Effect Transition [Line Items]
Deferred revenue, current portion												$ 7,242
Deferred revenue, net of current portion												9,328
Accumulated deficit												(2,079,475)
ASU 2014-09 Revenue from Contracts with Customers | Balances Without Adoption of New Revenue Standard
Revenue Initial Application Period Cumulative Effect Transition [Line Items]
Deferred revenue, current portion	$ 3,496								3,496
Deferred revenue, net of current portion	18,451								18,451
Accumulated deficit	(2,859,049)								(2,859,049)
Net loss									$ (711,364)
Net loss per common share — basic and diluted									$ (7.07)
ASU 2014-09 Revenue from Contracts with Customers | Balances Without Adoption of New Revenue Standard | Net Revenues from Collaborators
Revenue Initial Application Period Cumulative Effect Transition [Line Items]
Revenues									$ 112,506
ASU 2014-09 Revenue from Contracts with Customers | Effect of Change Higher/(Lower)
Revenue Initial Application Period Cumulative Effect Transition [Line Items]
Deferred revenue, current portion												(34,463)
Deferred revenue, net of current portion	(17,993)								(17,993)			(33,747)
Accumulated deficit	$ (18,077)								(18,077)			$ 68,210
Net loss									$ 50,133
Net loss per common share — basic and diluted									$ 0.50
ASU 2014-09 Revenue from Contracts with Customers | Effect of Change Higher/(Lower) | Net Revenues from Collaborators
Revenue Initial Application Period Cumulative Effect Transition [Line Items]
Revenues									$ (50,133)

Summary of Significant Accou_15

Summary of Significant Accounting Policies - Subsequent Events - Additional Information (Detail) - $ / shares	1 Months Ended
	Jan. 31, 2019	Nov. 30, 2017	May 31, 2017
Subsequent Event [Line Items]
Issuance of common stock, net of offering costs (in shares)		6,440,000	5,000,000
Underwritten public offering amount per share		$ 125	$ 71.87
Subsequent Event
Subsequent Event [Line Items]
Issuance of common stock, net of offering costs (in shares)	5,000,000
Underwritten public offering amount per share	$ 77.50

Product Revenues, Net - Additio

Product Revenues, Net - Additional Information (Detail) - USD ($) $ in Thousands	3 Months Ended								12 Months Ended
	Dec. 31, 2018	Sep. 30, 2018	Jun. 30, 2018	Mar. 31, 2018	Dec. 31, 2017	Sep. 30, 2017	Jun. 30, 2017	Mar. 31, 2017	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Disaggregation Of Revenue [Line Items]
Revenues	$ 21,033	$ 2,069	$ 29,907	$ 21,899	$ 37,924	$ 17,096	$ 15,932	$ 18,960	$ 74,908	$ 89,912	$ 47,159
Product Revenues, Net
Disaggregation Of Revenue [Line Items]
Revenues									$ 12,535

Product Revenues, Net - Summary

Product Revenues, Net - Summary of Balances and Activity in Each Product Revenue Allowance and Reserve Category (Detail) - ONPATTRO $ in Thousands	12 Months Ended
	Dec. 31, 2018USD ($)
Movement in Valuation Allowances and Reserves [Roll Forward]
Provision related to current period sales	$ 5,030
Credit or payments made during the period	(1,050)
Total	3,980
Chargebacks
Movement in Valuation Allowances and Reserves [Roll Forward]
Provision related to current period sales	1,553
Credit or payments made during the period	(640)
Total	913
Returns Reserve
Movement in Valuation Allowances and Reserves [Roll Forward]
Provision related to current period sales	2,528
Total	2,528
Trade Discounts and Allowances
Movement in Valuation Allowances and Reserves [Roll Forward]
Provision related to current period sales	292
Credit or payments made during the period	(74)
Total	218
Returns Reserve
Movement in Valuation Allowances and Reserves [Roll Forward]
Provision related to current period sales	106
Total	106
Other Incentives
Movement in Valuation Allowances and Reserves [Roll Forward]
Provision related to current period sales	551
Credit or payments made during the period	(336)
Total	$ 215

Revenue from Collaborators (Det

Revenue from Collaborators (Detail) - USD ($) $ in Thousands	3 Months Ended								12 Months Ended
	Dec. 31, 2018	Sep. 30, 2018	Jun. 30, 2018	Mar. 31, 2018	Dec. 31, 2017	Sep. 30, 2017	Jun. 30, 2017	Mar. 31, 2017	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Revenues	$ 21,033	$ 2,069	$ 29,907	$ 21,899	$ 37,924	$ 17,096	$ 15,932	$ 18,960	$ 74,908	$ 89,912	$ 47,159
Net Revenues from Collaborators
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Revenues									62,373	89,912	47,159
Net Revenues from Collaborators | Prior Revenue Standard | ASU 2014-09 Revenue from Contracts with Customers
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Revenues									112,506
Net Revenues from Collaborators | Sanofi Genzyme
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Revenues									46,000	54,625	32,015
Net Revenues from Collaborators | Sanofi Genzyme | Prior Revenue Standard | ASU 2014-09 Revenue from Contracts with Customers
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Revenues									91,738
Net Revenues from Collaborators | Vir
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Revenues									12,778	1,464
Net Revenues from Collaborators | Vir | Prior Revenue Standard | ASU 2014-09 Revenue from Contracts with Customers
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Revenues									12,778
Net Revenues from Collaborators | MDCO
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Revenues									2,789	30,217	11,220
Net Revenues from Collaborators | MDCO | Prior Revenue Standard | ASU 2014-09 Revenue from Contracts with Customers
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Revenues									7,184
Net Revenues from Collaborators | Other
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Revenues									806	$ 3,606	$ 3,924
Net Revenues from Collaborators | Other | Prior Revenue Standard | ASU 2014-09 Revenue from Contracts with Customers
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Revenues									$ 806

Balance of Contract Liabilities

Balance of Contract Liabilities Related to Collaboration Agreements (Detail) - USD ($) $ in Thousands	Dec. 31, 2018	Jan. 01, 2018
Contract liabilities:
Deferred revenues	$ 3,954	$ 16,570

Change in Contract Liability Ba

Change in Contract Liability Balance Related to Collaboration Agreements (Detail) $ in Thousands	12 Months Ended
	Dec. 31, 2018USD ($)
Revenue recognized in the period from:
Amounts included in contract liability at the beginning of the period	$ 16,570

Schedule of Research and Develo

Schedule of Research and Development Expenses Incurred by Type that are Directly Attributable to Collaboration Agreements (Detail) - USD ($) $ in Thousands		12 Months Ended
		Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Total research and development expenses	[1]	$ 505,420	$ 390,635	$ 382,392
Sanofi Genzyme
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Total research and development expenses		43,219	184,703	160,580
Vir
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Total research and development expenses		16,071	2,060
MDCO
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Total research and development expenses		1,869	5,527	1,275
Ionis
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Total research and development expenses		3,247	3,250	525
Clinical trial and manufacturing | Sanofi Genzyme
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Total research and development expenses		36,600	174,901	150,179
Clinical trial and manufacturing | Vir
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Total research and development expenses		7,272	1,134
Clinical trial and manufacturing | MDCO
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Total research and development expenses		1,664	5,421	1,211
External services | Sanofi Genzyme
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Total research and development expenses		5,340	4,475	7,366
External services | Vir
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Total research and development expenses		8,251	926
External services | MDCO
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Total research and development expenses		2
External services | Ionis
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Total research and development expenses		2,150	3,250
Other | Sanofi Genzyme
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Total research and development expenses		1,279	5,327	3,035
Other | Vir
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Total research and development expenses		548
Other | MDCO
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Total research and development expenses		203	$ 106	64
Other | Ionis
Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]
Total research and development expenses		$ 1,097		$ 525
[1]	Stock-based compensation expenses included in operating costs and expenses are as follows: Research and development $80,509 $51,872 $42,946 Selling, general and administrative 77,243 40,947 32,582

Significant Agreements - Additi

Significant Agreements - Additional Information (Detail)

Jan. 01, 2018USD ($)

Jan. 06, 2015USD ($)ProgramLicense

Jan. 14, 2014USD ($)

Oct. 31, 2012USD ($)

Jan. 31, 2018USD ($)MilestonePayment

Nov. 30, 2017$ / sharesshares

May 31, 2017$ / sharesshares

Jan. 31, 2017USD ($)

Feb. 29, 2016USD ($)shares

Jul. 31, 2015

Jan. 31, 2015USD ($)shares

Mar. 31, 2014USD ($)shares

Feb. 28, 2014USD ($)$ / sharesshares

Feb. 28, 2013USD ($)

Dec. 31, 2018USD ($)

Sep. 30, 2018USD ($)

Jun. 30, 2018USD ($)

Mar. 31, 2018USD ($)

Dec. 31, 2017USD ($)

Sep. 30, 2017USD ($)

Jun. 30, 2017USD ($)

Mar. 31, 2017USD ($)

Dec. 31, 2014USD ($)

Dec. 31, 2013USD ($)

Sep. 30, 2018USD ($)

Dec. 31, 2018USD ($)

Dec. 31, 2017USD ($)

Dec. 31, 2016USD ($)

Dec. 31, 2014USD ($)

Dec. 31, 2016USD ($)

Jan. 06, 2018USD ($)

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Deferred revenue

$ 16,570,000

$ 3,954,000

$ 3,954,000

Revenues recognized

21,033,000

$ 2,069,000

$ 29,907,000

$ 21,899,000

$ 37,924,000

$ 17,096,000

$ 15,932,000

$ 18,960,000

74,908,000

$ 89,912,000

$ 47,159,000

Issuance of common stock, net of offering costs (in shares) | shares

6,440,000

5,000,000

Proceeds from issuance of common stock to Sanofi Genzyme

21,381,000

14,301,000

Underwritten public offering amount per share | $ / shares

$ 125

$ 71.87

Research and Development

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

License fee

8,000,000

7,700,000

$ 2,400,000

Ionis

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Collaborative agreement termination notice period

90 days

Prior Revenue Standard | ASU 2014-09 Revenue from Contracts with Customers

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Deferred revenue

23,400,000

Product Alliances | MDCO

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Upfront fee received

25,000,000

$ 25,000,000

Amount earned upon achievement of milestone

30,000,000

20,000,000

$ 10,000,000

30,000,000

Maximum number of potential future milestones

180,000,000

Potential future payment for the achievement of certain development milestones

30,000,000

Potential future payment for the achievement of specified commercialization milestones

100,000,000

Transaction price

72,900,000

Cost-share reimbursements, net of payments included in transaction price

17,900,000

Potential future payment for the achievement of specified regulatory milestones

$ 50,000,000

Next potential milestone payment

25,000,000

Milestones earned included in transaction price

0

Cost incurred

$ 17,800,000

Total costs expected

$ 17,900,000

$ 17,900,000

Product Alliances | Maximum | MDCO

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Estimated range of expiration for fundamental patents

2,028

Product Alliances | Minimum | MDCO

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Estimated range of expiration for fundamental patents

2,016

Product Alliances | Prior Revenue Standard | ASU 2014-09 Revenue from Contracts with Customers | MDCO

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Deferred revenue

5,700,000

2018 Restructured Agreement Related to TTR Programs

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Deferred revenue

2,900,000

2018 Restructured Agreement Related to TTR Programs | Prior Revenue Standard | ASU 2014-09 Revenue from Contracts with Customers

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Deferred revenue

25,800,000

2018 Restructured Agreement

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Maximum funding for development and commercialization costs for fitusiran, during transition period

$ 50,000,000

2018 Restructured Agreement | Fitusiran

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Total Cost Incurred in Transition

$ 38,000,000

2018 Restructured Agreement | Prior Revenue Standard | Fitusiran | ASU 2014-09 Revenue from Contracts with Customers

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Incremental to transaction price

22,800,000

Discovery and Development Alliances | Ionis

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Number of programs Providing exclusive RNA therapeutic license rights | Program

4

Potential future payment upon the occurrence of achievement of specified development and regulatory milestones

$ 3,400,000

Number of licensed products | License

10

Additional number of licensed products | License

1

Discovery and Development Alliances | Ionis | Up Front Payment | Research and Development

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

License fee

$ 5,000,000

Discovery and Development Alliances | Ionis | Milestone Payments | Research and Development

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Potential future payment upon the occurrence of achievement of specified development and regulatory milestones

3,400,000

Discovery and Development Alliances | Ionis | Therapeutic target | Research and Development

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

License fee

$ 500,000

Sanofi Genzyme

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Upfront fee received

$ 22,500,000

Amount earned upon achievement of milestone

$ 11,000,000

Issuance of common stock, net of offering costs (in shares) | shares

344,448

8,766,338

Proceeds from issuance of common stock to Sanofi Genzyme

$ 23,000,000

$ 700,000,000

21,400,000

Voting percentage

20.00%

Minimum percentage of ownership interest terminate

7.50%

Agreement lock-up period, extension term

2 years

Agreement lock-up period

6 months

Percentage of acquired outstanding common stock for Genzyme to appoint individual to board of directors

20.00%

Underwritten public offering amount per share | $ / shares

$ 85.72

Fair value of shares issued

$ 751,500,000

Excess of fair value over cash received for stock issuance

51,500,000

Provision for (Benefit from) income taxes

$ 15,200,000

Sanofi Genzyme | Alnylam Pharmaceuticals Inc

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Percentage ownership interest owned by noncontrolling owners

10.00%

10.00%

Sanofi Genzyme | Concurrent Private Placement

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Issuance of common stock, net of offering costs (in shares) | shares

297,501

744,566

Proceeds from issuance of common stock to Sanofi Genzyme

$ 70,700,000

Sanofi Genzyme | Compensatory Purposes

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Issuance of common stock, net of offering costs (in shares) | shares

205,030

196,251

Proceeds from issuance of common stock to Sanofi Genzyme

$ 14,300,000

$ 18,300,000

Sanofi Genzyme | Following the two-year anniversary

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Number of trailing days on which average is calculated

10 days

Sanofi Genzyme | Maximum

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Agreement to acquire outstanding shares of common stock percentage

30.00%

Sanofi Genzyme | Maximum | Following the two-year anniversary

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Percentage of sale of initial shares

25.00%

Sanofi Genzyme | Minimum

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Agreement to acquire outstanding shares of common stock percentage

5.00%

Percentage of ownership interest

30.00%

Sanofi Genzyme | Minimum | Following the two-year anniversary

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Percentage of market price per share of common stock compared to share of common stock at closing of stock purchase

100.00%

Sanofi Genzyme | Revusiran

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Amount earned upon achievement of milestone

$ 25,000,000

Sanofi Genzyme | Fitusiran

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Cost-share reimbursements, net of payments included in transaction price

147,300,000

Sanofi Genzyme | Product Alliances

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Upfront fee received

$ 22,500,000

Amount earned upon achievement of milestone

11,000,000

Sanofi Genzyme | Product Alliances | Prior Revenue Standard

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Deferred revenue

$ 33,500,000

Sanofi Genzyme | Regional Collaboration Product

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Percentage of sharing in development cost

20.00%

Maximum number of potential future milestones

$ 75,000,000

Potential future payment for the achievement of certain development milestones

55,000,000

Potential future payment for the achievement of specified commercialization milestones

$ 20,000,000

Royalty rate

20.00%

Sanofi Genzyme | Co-developed/ Co-commercialized Collaboration Product

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Percentage of sharing in development cost

50.00%

Royalty rate

20.00%

Received incremental share of co-development costs for exercise of right, fitusiran

$ 6,000,000

Expected first milestone payment to be received fitusiran

$ 25,000,000

$ 25,000,000

Sanofi Genzyme | Co-developed/ Co-commercialized Collaboration Product | Revusiran

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Amount earned upon achievement of milestone

$ 25,000,000

Sanofi Genzyme | Global Collaboration Product

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Percentage of sharing in development cost

100.00%

Maximum number of potential future milestones

$ 200,000,000

Potential future payment for the achievement of certain development milestones

100,000,000

Potential future payment for the achievement of specified commercialization milestones

$ 100,000,000

Royalty rate

20.00%

Sanofi Genzyme | AT3 License Terms and the Exclusive TTR License

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Maximum funding for development and commercialization costs for fitusiran, during transition period

$ 50,000,000

Sanofi Genzyme | TTR License

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Transaction price

127,600,000

Sanofi Genzyme | TTR License | ONPATTRO | Japan

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Royalty rate

25.00%

Sanofi Genzyme | TTR License | ONPATTRO | Maximum | Excluding U.S., Canada and Western Europe

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Royalty rate

25.00%

Sanofi Genzyme | TTR License | Revusiran

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Cost-share reimbursements, net of payments included in transaction price

57,000,000

Sanofi Genzyme | TTR License | TTRsc02 | Maximum

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Royalty rate

30.00%

Sanofi Genzyme | TTR License | TTRsc02 | Minimum

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Royalty rate

15.00%

Sanofi Genzyme | TTR License | Back-up Products | Maximum

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Royalty rate

15.00%

Sanofi Genzyme | TTR License | Patisiran

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Cost-share reimbursements, net of payments included in transaction price

63,600,000

Sanofi Genzyme | AT3 License Terms

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Number of milestone payments required | MilestonePayment

1

Expected milestone payment to be received fitusiran

$ 50,000,000

Sanofi Genzyme | AT3 License Terms | Back-up Products | Maximum

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Royalty rate

15.00%

Sanofi Genzyme | AT3 License Terms | Fitusiran | Maximum

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Royalty rate

30.00%

Sanofi Genzyme | AT3 License Terms | Fitusiran | Minimum

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Royalty rate

15.00%

Sanofi Genzyme | 2018 Restructured Agreement | Fitusiran

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Amount earned upon achievement of milestone

$ 50,000,000

Deferred revenue

$ 600,000

Transaction price

$ 37,600,000

Revenues recognized

37,600,000

Sanofi Genzyme | 2018 Restructured Agreement | Prior Revenue Standard | Fitusiran | ASU 2014-09 Revenue from Contracts with Customers

Collaborative Arrangements and Non-collaborative Arrangement Transactions [Line Items]

Revenues recognized

$ 60,300,000

Schedule of Inventory (Detail)

Schedule of Inventory (Detail) $ in Thousands	Dec. 31, 2018USD ($)
Inventory Disclosure [Abstract]
Raw materials	$ 8,709
Work in process	15,262
Finished goods	97
Total inventory	$ 24,068

Fair Value of Assets Measured o

Fair Value of Assets Measured on a Recurring Basis (Detail) - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Available for sale debt securities, Fair value disclosure	$ 662,803	$ 1,059,176
Marketable equity securities	1,206
Recurring
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Marketable equity securities	1,206
Total	989,212	1,577,988
Recurring | U.S. treasury securities
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Cash equivalents	221,281	62,855
Available for sale debt securities, Fair value disclosure	325,227	200,475
Recurring | Money Market Funds
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Cash equivalents	102,445	122,986
Restricted cash	1,477	1,471
Recurring | Certificate of deposit
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Available for sale debt securities, Fair value disclosure	8,951	30,200
Recurring | Commercial paper
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Cash equivalents		82,262
Available for sale debt securities, Fair value disclosure	57,197	56,951
Recurring | Corporate notes
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Cash equivalents		18,116
Available for sale debt securities, Fair value disclosure	232,410	373,252
Recurring | U.S. government-sponsored enterprise securities
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Cash equivalents		231,122
Available for sale debt securities, Fair value disclosure	39,018	398,298
Recurring | Quoted Prices in Active Markets (Level 1)
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Marketable equity securities	1,206
Total	105,128	124,457
Recurring | Quoted Prices in Active Markets (Level 1) | Money Market Funds
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Cash equivalents	102,445	122,986
Restricted cash	1,477	1,471
Recurring | Significant Observable Inputs (Level 2)
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Total	884,084	1,453,531
Recurring | Significant Observable Inputs (Level 2) | U.S. treasury securities
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Cash equivalents	221,281	62,855
Available for sale debt securities, Fair value disclosure	325,227	200,475
Recurring | Significant Observable Inputs (Level 2) | Certificate of deposit
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Available for sale debt securities, Fair value disclosure	8,951	30,200
Recurring | Significant Observable Inputs (Level 2) | Commercial paper
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Cash equivalents		82,262
Available for sale debt securities, Fair value disclosure	57,197	56,951
Recurring | Significant Observable Inputs (Level 2) | Corporate notes
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Cash equivalents		18,116
Available for sale debt securities, Fair value disclosure	232,410	373,252
Recurring | Significant Observable Inputs (Level 2) | U.S. government-sponsored enterprise securities
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Cash equivalents		231,122
Available for sale debt securities, Fair value disclosure	$ 39,018	$ 398,298

Fair Value Measurements - Addit

Fair Value Measurements - Additional Information (Detail) $ in Millions	Dec. 31, 2018USD ($)
Significant Unobservable Inputs (Level 3)
Fair Value, Assets and Liabilities Measured on Recurring and Nonrecurring Basis [Line Items]
Fair value of long-term debt	$ 30.1

Summary of Company's Marketable

Summary of Company's Marketable Debt Securities (Detail) - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	$ 663,224	$ 1,060,817
Gross Unrealized Gains	1	12
Gross Unrealized Losses	(422)	(1,653)
Fair Value	662,803	1,059,176
Certificate of deposit
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	8,951	30,200
Fair Value	8,951	30,200
Commercial paper
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	57,197	56,951
Fair Value	57,197	56,951
Corporate notes
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	232,695	373,736
Gross Unrealized Gains		11
Gross Unrealized Losses	(285)	(495)
Fair Value	232,410	373,252
U.S. government-sponsored enterprise securities
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	39,031	399,281
Gross Unrealized Losses	(13)	(983)
Fair Value	39,018	398,298
U.S. treasury securities
Schedule of Available-for-sale Securities [Line Items]
Amortized Cost	325,350	200,649
Gross Unrealized Gains	1	1
Gross Unrealized Losses	(124)	(175)
Fair Value	$ 325,227	$ 200,475

Summary of Available-For-Sale D

Summary of Available-For-Sale Debt Securities by Contractual Maturity (Detail) - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
Amortized Cost
Less than one year	$ 663,224
Amortized Cost	663,224	$ 1,060,817
Fair Value
Less than one year	662,803
Total	$ 662,803	$ 1,059,176

Property Plant and Equipment Ne

Property Plant and Equipment Net (Detail) - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
Property Plant And Equipment [Abstract]
Laboratory equipment	$ 43,427	$ 40,462
Computer equipment and software	13,495	9,608
Furniture and fixtures	7,238	5,844
Leasehold improvements	65,928	50,612
Land	9,080	9,080
Construction in progress	260,975	133,645
Property, Plant and Equipment Gross	400,143	249,251
Less: accumulated depreciation	(79,485)	(67,351)
Property, Plant and Equipment, Net	$ 320,658	$ 181,900

Property Plant and Equipment _2

Property Plant and Equipment Net - Additional Information (Detail) $ in Thousands	12 Months Ended
	Dec. 31, 2018USD ($)	Dec. 31, 2017USD ($)	Dec. 31, 2016USD ($)	Apr. 30, 2016a
Property, Plant and Equipment [Line Items]
Depreciation expense	$ 12,800	$ 11,900	$ 9,600
Property, plant and equipment, net	320,658	181,900
Norton, Massachusetts
Property, Plant and Equipment [Line Items]
Undeveloped land acquired | a				12
Norton, Massachusetts | Land and costs related to the construction of manufacturing facility
Property, Plant and Equipment [Line Items]
Property, plant and equipment, net	$ 227,700	$ 140,500

Fixed and Cancelable Payments u

Fixed and Cancelable Payments under Existing License and Other Technology Agreements (Detail) $ in Thousands	Dec. 31, 2018USD ($)
Commitments And Contingencies Disclosure [Abstract]
2,019	$ 1,453
2,020	795
2,021	745
2,022	545
2,023	525
Thereafter	525
Total	$ 4,588

Commitments and Contingencies -

Commitments and Contingencies - Additional Information (Detail)

Apr. 01, 2019USD ($)

Jan. 01, 2019

Sep. 27, 2018RenewalOption

Aug. 14, 2018USD ($)RenewalOption

Apr. 18, 2018USD ($)shares

Apr. 29, 2016USD ($)

Sep. 26, 2003ft²

Jan. 31, 2019USD ($)

Dec. 31, 2018USD ($)

Dec. 31, 2017USD ($)

Aug. 31, 2016RenewalOption

May 31, 2015USD ($)ft²RenewalOption$ / ft²

Apr. 30, 2015USD ($)ft²RenewalOption

Mar. 31, 2015USD ($)

Sep. 30, 2022USD ($)

Mar. 31, 2020

Dec. 31, 2018USD ($)

Dec. 31, 2017USD ($)

Dec. 31, 2016USD ($)

Feb. 10, 2012ft²

Commitments And Contingencies [Line Items]

Maximum potential future milestone payments to third parties

$ 53,700,000

Cost of base building and tenant improvement, received

(25,350,000)

$ (2,145,000)

Restricted investments

$ 44,825,000

$ 30,000,000

44,825,000

$ 30,000,000

Rent expense

40,600,000

18,700,000

$ 15,900,000

Repayment of outstanding principal amount in full

120,000,000

Litigation settlement, common stock issuable from other party | shares

983,208

Dicerna Pharmaceuticals, Inc

Commitments And Contingencies [Line Items]

Litigation settlement, settlement agreement date

April 18, 2018

Litigation settlement amount

$ 25,000,000

2,500,000

13,000,000

Litigation settlement, common stock value

10,000,000

Additional payment due from litigation settlement

$ 13,000,000

Litigation settlement payment period

4 years

Dicerna Pharmaceuticals, Inc | Up Front Payment

Commitments And Contingencies [Line Items]

Litigation settlement amount

$ 2,000,000

Subsequent Event | Dicerna Pharmaceuticals, Inc

Commitments And Contingencies [Line Items]

Litigation settlement amount

$ 10,500,000

Bank of America N.A

Commitments And Contingencies [Line Items]

Cash collateral required for principal amount outstanding, percentage

100.00%

Bank of America N.A | Term Loan Facility

Commitments And Contingencies [Line Items]

Line of credit facility, maximum borrowing capacity

$ 120,000,000

Repayment of outstanding principal amount in full

120,000,000

Line of credit facility, expiration date

Apr. 29, 2021

Bank of America N.A | Term Loan Facility | LIBOR

Commitments And Contingencies [Line Items]

Debt instrument, basis spread on variable rate

0.45%

Wells Fargo Bank, National Association

Commitments And Contingencies [Line Items]

Restricted investments

30,000,000

30,000,000

30,000,000

30,000,000

Cash collateral required for principal amount outstanding, percentage

100.00%

Wells Fargo Bank, National Association | Term Loan Facility

Commitments And Contingencies [Line Items]

Line of credit facility, maximum borrowing capacity

$ 30,000,000

Line of credit facility, expiration date

Apr. 29, 2021

Wells Fargo Bank, National Association | Term Loan Facility | LIBOR

Commitments And Contingencies [Line Items]

Debt instrument, basis spread on variable rate

0.45%

Other Assets

Commitments And Contingencies [Line Items]

Restricted cash

1,500,000

$ 1,500,000

1,500,000

$ 1,500,000

Maximum | Oligonucleotide | Dicerna Pharmaceuticals, Inc

Commitments And Contingencies [Line Items]

Restriction period in development and other activities defined set of targets

4 years

Maximum | Silence Litigation | ONPATTRO | Subsequent Event

Commitments And Contingencies [Line Items]

Percentage of royalty on annual net sales

1.00%

Minimum | Oligonucleotide | Dicerna Pharmaceuticals, Inc

Commitments And Contingencies [Line Items]

Restriction period in development and other activities defined set of targets

18 months

Minimum | Silence Litigation | ONPATTRO | Subsequent Event

Commitments And Contingencies [Line Items]

Percentage of royalty on annual net sales

0.33%

Third Street Lease

Commitments And Contingencies [Line Items]

Area of office and laboratory space held under lease | ft²

129,000

Lease extended expiration date

Jan. 31, 2034

Sep. 30, 2021

Lease extension period

12 years 4 months

Number of lease extension options | RenewalOption

2

Amended lease extension period

5 years

Third Street Lease | Scenario Forecast

Commitments And Contingencies [Line Items]

Facility lease annual rent

$ 10,500,000

Facility lease percentage of annual rent increase thereafter

2.50%

Third Street Lease | Maximum

Commitments And Contingencies [Line Items]

Tenant improvement allowance from landlord

$ 8,400,000

BMR-665 Concord Avenue Lease

Commitments And Contingencies [Line Items]

Area of office and laboratory space held under lease | ft²

15,000

Lease extended expiration date

Aug. 31, 2022

Number of lease extension options | RenewalOption

1

Amended lease extension period

5 years

BMR-675 West Kendall Lease

Commitments And Contingencies [Line Items]

Area of office and laboratory space held under lease | ft²

295,000

Number of lease extension options | RenewalOption

2

Lease term

15 years

Lease renewal options period

5 years

Facility lease annual rent for the first year

$ 19,800,000

Facility lease percentage of annual rent increase after first year

3.00%

Cost of base building and tenant improvement

$ 56,100,000

Cost of base building and tenant improvement, received

25,400,000

Cost of base building and tenant improvement, due

12,500,000

12,500,000

Restricted investments

$ 14,800,000

14,800,000

101 Main Street Leases

Commitments And Contingencies [Line Items]

Area of office and laboratory space held under lease | ft²

72,000

Lease Expiration Date

Mar. 31, 2019

Operating lease annual rent increase per square foot | $ / ft²

1

101 Main Street Leases | Scenario Forecast

Commitments And Contingencies [Line Items]

Facility lease annual rent

$ 2,100,000

Facility lease percentage of annual rent increase thereafter

2.00%

101 Main Street Initial Leases

Commitments And Contingencies [Line Items]

Lease extended expiration date

Mar. 31, 2024

Lease extension period

5 years

Number of lease extension options | RenewalOption

1

Operating lease renewal options period

5 years

Operating lease annual rent for the first year

$ 1,700,000

101 Main Street Additional Leases

Commitments And Contingencies [Line Items]

Number of lease extension options | RenewalOption

1

Operating lease renewal options period

5 years

Operating lease term

5 years 6 months

Operating lease annual rent for the first year

$ 3,500,000

Development Milestones

Commitments And Contingencies [Line Items]

Maximum potential future milestone payments to third parties

9,900,000

Regulatory Milestones

Commitments And Contingencies [Line Items]

Maximum potential future milestone payments to third parties

40,200,000

Commercial Milestones

Commitments And Contingencies [Line Items]

Maximum potential future milestone payments to third parties

$ 3,600,000

Future Minimum Lease Payments u

Future Minimum Lease Payments under Non-Cancelable Lease (Detail) $ in Thousands	Dec. 31, 2018USD ($)
Commitments And Contingencies Disclosure [Abstract]
2,019	$ 32,228
2,020	34,826
2,021	34,410
2,022	34,826
2,023	35,270
Thereafter	390,455
Total	$ 562,015

Stockholders Equity - Additiona

Stockholders Equity - Additional Information (Detail) - USD ($) $ / shares in Units, $ in Thousands	1 Months Ended			12 Months Ended
	Jan. 31, 2019	Nov. 30, 2017	May 31, 2017	Dec. 31, 2017	Dec. 31, 2018
Stockholders Equity [Line Items]
Preferred stock, shares authorized				5,000,000	5,000,000
Preferred stock, par value				$ 0.01	$ 0.01
Preferred stock, shares outstanding				0	0
Issuance of common stock, net of offering costs (in shares)		6,440,000	5,000,000
Underwritten public offering amount per share		$ 125	$ 71.87
Issuance of common stock, net of offering costs		$ 784,500	$ 355,200	$ 1,139,625
Underwriting discounts and commissions and other offering expenses		$ 20,500	$ 4,200
Subsequent Event
Stockholders Equity [Line Items]
Issuance of common stock, net of offering costs (in shares)	5,000,000
Underwritten public offering amount per share	$ 77.50
Issuance of common stock, net of offering costs	$ 381,900
Underwriting discounts and commissions and other offering expenses	$ 5,600

Stock-Based Compensation - Addi

Stock-Based Compensation - Additional Information (Detail) - USD ($)

May 08, 2017

Feb. 06, 2017

Sep. 19, 2016

Aug. 31, 2018

Jan. 31, 2016

Dec. 31, 2018

Dec. 31, 2017

Dec. 31, 2016

May 31, 2018

May 31, 2017

May 31, 2015

Apr. 30, 2015

Jun. 30, 2010

Dec. 31, 2004

Share-based Compensation Arrangement by Share-based Payment Award [Line Items]

Shares of common stock reserved for future issuance under stock options

17,491,117

Option vesting percentage on the first anniversary of grant date

25.00%

Option vesting percentage at the end of each successive three-month period

6.25%

Stock-based compensation

$ 157,752,000

$ 92,819,000

$ 75,528,000

Employee stock purchase plan, offering period

6 months

Change in Control Agreements | Expense Associated with Equity Grants Modifications

Share-based Compensation Arrangement by Share-based Payment Award [Line Items]

Stock-based compensation

$ 20,800,000

1,100,000

Stock Options

Share-based Compensation Arrangement by Share-based Payment Award [Line Items]

Shares of common stock reserved for future issuance under stock options

12,572,522

Equity awards, term

10 years

Restricted stock units

Share-based Compensation Arrangement by Share-based Payment Award [Line Items]

Shares of common stock reserved for future issuance under stock options

36,083

Additional Equity Awards Available for Future Grant

Share-based Compensation Arrangement by Share-based Payment Award [Line Items]

Shares of common stock reserved for future issuance under stock options

4,433,370

Employee Stock Purchase Plan

Share-based Compensation Arrangement by Share-based Payment Award [Line Items]

Stock incentive plan, shares authorized

1,215,789

715,789

315,789

Shares of common stock reserved for future issuance under stock options

449,142

Stock-based compensation

$ 2,842,000

$ 2,155,000

$ 1,360,000

Employee stock purchase plan, purchase price as a percentage of common stock closing price

85.00%

Employee stock purchase plan, shares issued

78,085

103,666

53,499

Weighted average fair value awards granted

$ 35.67

$ 17.10

$ 24.90

Expected volatility

63.00%

91.00%

55.00%

Expected option life

6 months

6 months

6 months

Risk-free interest rate, approximate

2.00%

0.70%

0.10%

Performance-based stock options

Share-based Compensation Arrangement by Share-based Payment Award [Line Items]

Stock-based compensation

$ 56,419,000

$ 23,260,000

$ 8,337,000

Aggregate intrinsic value of stock option exercised

$ 8,000,000

$ 1,800,000

$ 35,000

Stock options vested

763,982

614,796

159,122

Performance-based stock options | ONPATTRO

Share-based Compensation Arrangement by Share-based Payment Award [Line Items]

Stock-based compensation

$ 16,100,000

Estimated share-based compensation expense

30,300,000

Performance-based stock options | On-hire executive grant

Share-based Compensation Arrangement by Share-based Payment Award [Line Items]

Stock options granted

25,000

25,000

Inducement Equity Grants

Share-based Compensation Arrangement by Share-based Payment Award [Line Items]

Equity awards, term

10 years

10 years

10 years

Stock options granted

150,000

150,000

Time-vested options under Inducement Equity Grants

Share-based Compensation Arrangement by Share-based Payment Award [Line Items]

Option vesting percentage on the first anniversary of grant date

25.00%

25.00%

25.00%

Option vesting percentage at the end of each successive three-month period

6.25%

6.25%

6.25%

Stock options granted

125,000

50,000

125,000

Performance-based stock options under Inducement Equity Grants

Share-based Compensation Arrangement by Share-based Payment Award [Line Items]

Stock options granted

25,000

25,000

Time-based stock options

Share-based Compensation Arrangement by Share-based Payment Award [Line Items]

Stock-based compensation

$ 83,403,000

$ 61,802,000

$ 62,800,000

Weighted average fair value of stock options granted

$ 66.49

$ 44.76

$ 31.66

Aggregate intrinsic value of stock option exercised

$ 87,100,000

$ 111,300,000

$ 22,000,000

January 2016 Performance-Based Restricted Stock Unit

Share-based Compensation Arrangement by Share-based Payment Award [Line Items]

Stock-based compensation

$ 11,800,000

Restricted Stock Awards Granted

172,718

Fair value of equity awards granted

$ 16,100,000

Restricted stock awards vested

124,833

Restricted stock awards vested, fair value

$ 11,400,000

Minimum

Share-based Compensation Arrangement by Share-based Payment Award [Line Items]

Expected option life

5 years 8 months 12 days

5 years 8 months 12 days

3 years 6 months

Minimum | Performance-based stock options

Share-based Compensation Arrangement by Share-based Payment Award [Line Items]

Vesting period

1 year

Minimum | Performance-based stock options under Inducement Equity Grants

Share-based Compensation Arrangement by Share-based Payment Award [Line Items]

Vesting period

1 year

1 year

Maximum

Share-based Compensation Arrangement by Share-based Payment Award [Line Items]

Expected option life

7 years 2 months 12 days

7 years 2 months 12 days

7 years 6 months

Stock Incentive Plan 2009

Share-based Compensation Arrangement by Share-based Payment Award [Line Items]

Stock incentive plan, shares authorized

15,480,000

11,700,000

5,900,000

Stock Incentive Plan 2018

Share-based Compensation Arrangement by Share-based Payment Award [Line Items]

Stock incentive plan, shares authorized

3,500,000

Summary of Stock-Based Compensa

Summary of Stock-Based Compensation Expense (Detail) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Stock-based compensation	$ 157,752	$ 92,819	$ 75,528
Less: Stock-based compensation expense capitalized to inventory	(1,424)
Time-based stock options
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Stock-based compensation	83,403	61,802	62,800
Performance-based stock options
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Stock-based compensation	56,419	23,260	8,337
Time-based restricted stock units
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Stock-based compensation	538	541	497
Performance-based restricted stock units
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Stock-based compensation	13,144
ESPP share issuances
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Stock-based compensation	2,842	2,155	1,360
Other Equity Programs
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Stock-based compensation	1,345	1,946	1,846
Non-employee stock options
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Stock-based compensation	$ 1,485	$ 3,115	$ 688

Summary of Unrecognized Stock-B

Summary of Unrecognized Stock-Based Compensation Expense, Net of Estimated Forfeitures (Detail) $ in Thousands	12 Months Ended
	Dec. 31, 2018USD ($)
Time-based stock options
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Unrecognized Expense, Net of Estimated Forfeitures	$ 156,192
Weighted-average Recognition Period	2 years 6 months 10 days
Performance-based stock options
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Unrecognized Expense, Net of Estimated Forfeitures	$ 57,586
Time-based restricted stock units
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Unrecognized Expense, Net of Estimated Forfeitures	$ 769
Weighted-average Recognition Period	9 months 10 days
Performance-based restricted stock units
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Unrecognized Expense, Net of Estimated Forfeitures	$ 1,747
ESPP share issuances
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Unrecognized Expense, Net of Estimated Forfeitures	$ 984
Weighted-average Recognition Period	3 months 29 days

Valuation Assumptions for Stock

Valuation Assumptions for Stock Options (Detail)	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Risk-free interest rate, minimum	2.70%	1.90%	0.90%
Risk-free interest rate, maximum	2.90%	2.30%	2.20%
Expected volatility, minimum	64.00%	61.00%	55.00%
Expected volatility, maximum	67.00%	67.00%	65.00%
Minimum
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Expected option life	5 years 8 months 12 days	5 years 8 months 12 days	3 years 6 months
Maximum
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Expected option life	7 years 2 months 12 days	7 years 2 months 12 days	7 years 6 months

Stock Option and Inducement Gra

Stock Option and Inducement Grant Activity (Detail) $ / shares in Units, shares in Thousands, $ in Thousands	12 Months Ended
	Dec. 31, 2018USD ($)$ / sharesshares
Time-based stock options
Number of Options
Outstanding, December 31, 2017 | shares	9,101
Granted | shares	2,273
Exercised | shares	(1,181)
Cancelled | shares	(364)
Outstanding, December 31, 2018 | shares	9,829
Exercisable at December 31, 2018 | shares	5,734
Vested or expected to vest at December 31, 2018 | shares	9,327
Weighted-average Exercise Price
Outstanding, December 31, 2017 | $ / shares	$ 60.18
Granted | $ / shares	110.11
Exercised | $ / shares	46.92
Cancelled | $ / shares	82.89
Outstanding, December 31, 2018 | $ / shares	72.48
Exercisable at December 31, 2018 | $ / shares	58.90
Vested or expected to vest at December 31, 2018 | $ / shares	$ 71.36
Weighted-average Remaining Contractual Term (in years)
Outstanding, December 31, 2018	6 years 8 months 4 days
Exercisable at December 31, 2018	5 years 3 months 21 days
Vested or expected to vest at December 31, 2018	6 years 6 months 21 days
Aggregate Intrinsic Value
Outstanding, December 31, 2018 | $	$ 149,518
Exercisable at December 31, 2018 | $	127,051
Vested or expected to vest at December 31, 2018 | $	$ 147,144
Performance-based stock options
Number of Options
Outstanding, December 31, 2017 | shares	2,138
Granted | shares	912
Exercised | shares	(149)
Cancelled | shares	(157)
Outstanding, December 31, 2018 | shares	2,744
Exercisable at December 31, 2018 | shares	1,420
Weighted-average Exercise Price
Outstanding, December 31, 2017 | $ / shares	$ 69.14
Granted | $ / shares	119.13
Exercised | $ / shares	67.04
Cancelled | $ / shares	88.64
Outstanding, December 31, 2018 | $ / shares	84.75
Exercisable at December 31, 2018 | $ / shares	$ 74.29
Weighted-average Remaining Contractual Term (in years)
Outstanding, December 31, 2018	7 years 2 months 26 days
Exercisable at December 31, 2018	6 years 2 months 15 days
Aggregate Intrinsic Value
Outstanding, December 31, 2018 | $	$ 23,694
Exercisable at December 31, 2018 | $	$ 13,134

Schedule of Domestic and Foreig

Schedule of Domestic and Foreign Components of Loss before Income Taxes (Detail) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Income (Loss) Before Income Tax
Domestic	$ (573,245)	$ (378,293)	$ (350,704)
Foreign	(187,429)	(112,581)	(59,404)
Loss before income taxes	$ (760,674)	$ (490,874)	$ (410,108)

Schedule of Provision for Incom

Schedule of Provision for Income Taxes (Detail) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Current provision:
Foreign	$ (1,611)
Total current provision	(1,611)
Deferred benefit:
Federal	788
Total deferred benefit	788
Total provision for income taxes	$ (823)	$ 0	$ 0

Schedule of Components of Net D

Schedule of Components of Net Deferred Tax (Liability) Asset (Detail) - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
Deferred tax assets:
Net operating loss carryforwards	$ 506,574	$ 405,784
Research and development and ODC credits	220,776	192,094
AMT credits	788	788
Capitalized research and development and start-up costs	12,139	13,163
Deferred revenue		13,576
Deferred compensation	57,268	42,990
Property, plant and equipment, net		2,471
Intangible assets	50,121	9,018
Other	20,660	9,137
Total deferred tax assets	868,326	689,021
Deferred tax liabilities:
Property, plant and equipment, net	(6,550)
Unrealized gain on marketable securities	(903)	(765)
Deferred tax asset valuation allowance	(860,085)	$ (688,256)
Net deferred tax asset	$ 788

Schedule of Effective Income Ta

Schedule of Effective Income Tax Rate Differs from Statutory Federal Income Tax Rate (Detail)	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Effective Income Tax Rate Reconciliation, Percent
At U.S. federal statutory rate	21.00%	35.00%	35.00%
State taxes, net of federal effect	2.10%	3.80%	3.70%
Stock-based compensation	0.80%	3.30%	(1.40%)
Tax credits	4.20%	9.90%	11.80%
Other permanent items	(0.30%)	(1.00%)	(0.40%)
Foreign rate differential	(5.30%)	(8.10%)	(5.10%)
Tax reform change		(46.50%)
Revaluation of deferred credits due to rate change	(3.50%)
Other		(0.90%)
Valuation allowance	(19.00%)	7.90%	(40.10%)
Orphan drug credit
Effective Income Tax Rate Reconciliation, Percent
Tax credits		(3.40%)	(3.50%)

Income Taxes - Additional Infor

Income Taxes - Additional Information (Detail) - USD ($)	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Income Taxes [Line Items]
Increase (decrease) in valuation allowance	$ 171,800,000	$ 112,900,000	$ 177,900,000
Corporate tax rate	21.00%	35.00%	35.00%
Tax cuts and jobs act of 2017, provision to income tax expense in continuing operations and corresponding reduction in the valuation allowance		$ 227,900,000
Provision for income taxes	$ 823,000	0	$ 0
Tax cuts and jobs act of benefit for refundable credits	800,000
Foreign income taxes	$ 1,611,000
Net operating loss carryforwards expiration date	Dec. 31, 2038
Unrecognized tax benefits that, if recognized, would favorably impact our effective income tax rate	$ 0	0	0
Unrecognized tax benefits, interest and penalties	0	$ 0	$ 0
Federal
Income Taxes [Line Items]
Net operating loss carryforward	1,900,000,000
State and local jurisdiction
Income Taxes [Line Items]
Net operating loss carryforward	1,600,000,000
Carried forward indefinitely | Federal
Income Taxes [Line Items]
Net operating loss carryforward	$ 500,000,000
Earliest tax year
Income Taxes [Line Items]
Open tax year	2,015
Latest tax year
Income Taxes [Line Items]
Open tax year	2,018
Research and Development, Including Orphan Drug, and State Investments Tax Credit
Income Taxes [Line Items]
Tax credit carryforwards expiration year	2,038
Research and Development, Including Orphan Drug, and State Investments Tax Credit | Federal
Income Taxes [Line Items]
Tax credit carryforwards	$ 208,000,000
Research and Development, Including Orphan Drug, and State Investments Tax Credit | State and local jurisdiction
Income Taxes [Line Items]
Tax credit carryforwards	16,200,000
Alternative minimum tax
Income Taxes [Line Items]
Tax credit carryforwards	$ 800,000
Tax credits refundable year	2,021

Accrued Expenses (Detail)

Accrued Expenses (Detail) - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
Accrued Liabilities Current [Abstract]
Compensation and related	$ 37,301	$ 33,826
Clinical trial and manufacturing	36,500	20,004
Consulting and professional services	10,450	7,276
Product revenue allowances	2,696
Pre-clinical	2,138	239
Other	23,634	10,858
Accrued expenses	$ 112,719	$ 72,203

Schedule of Quarterly Financial

Schedule of Quarterly Financial Information (Detail) - USD ($) $ / shares in Units, shares in Thousands, $ in Thousands	3 Months Ended								12 Months Ended
	Dec. 31, 2018	Sep. 30, 2018	Jun. 30, 2018	Mar. 31, 2018	Dec. 31, 2017	Sep. 30, 2017	Jun. 30, 2017	Mar. 31, 2017	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Selected Quarterly Financial Information [Abstract]
Revenues	$ 21,033	$ 2,069	$ 29,907	$ 21,899	$ 37,924	$ 17,096	$ 15,932	$ 18,960	$ 74,908	$ 89,912	$ 47,159
Operating costs and expenses	241,389	256,627	222,261	169,304	185,227	142,896	136,406	125,471	889,581	590,000	471,746
Net loss	$ (211,441)	$ (245,282)	$ (163,560)	$ (141,214)	$ (142,227)	$ (122,937)	$ (118,420)	$ (107,290)	$ (761,497)	$ (490,874)	$ (410,108)
Net loss per common share — basic and diluted	$ (2.09)	$ (2.43)	$ (1.63)	$ (1.41)	$ (1.48)	$ (1.34)	$ (1.34)	$ (1.25)	$ (7.57)	$ (5.42)	$ (4.79)
Weighted-average common shares — basic and diluted	101,066	100,783	100,519	99,979	96,139	91,828	88,098	86,027	100,590	90,554	85,596