Ultragenyx Pharmaceutical (RARE) 10-K 20 Feb 19 2018 FY Annual report Financial data

Document and Entity Information

Document and Entity Information - USD ($) $ in Billions	12 Months Ended
	Dec. 31, 2018	Feb. 14, 2019	Jun. 30, 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	RARE
Entity Registrant Name	Ultragenyx Pharmaceutical Inc.
Entity Central Index Key	1,515,673
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		51,278,958
Entity Public Float			$ 3.2

CONSOLIDATED BALANCE SHEETS

CONSOLIDATED BALANCE SHEETS - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
Current assets:
Cash and cash equivalents	$ 113,432	$ 100,488
Short-term investments	346,274	134,005
Accounts receivable	12,740	5,172
Inventory	7,065	757
Prepaid expenses and other current assets	42,858	29,161
Total current assets	522,369	269,583
Property and equipment, net	20,046	21,837
Long-term investments		9,975
Intangible assets, net	129,223	141,545
Goodwill	44,406	44,406
Other assets	3,514	3,407
Total assets	719,558	490,753
Current liabilities:
Accounts payable	12,275	8,886
Accrued liabilities	62,450	62,128
Total current liabilities	74,725	71,014
Deferred tax liabilities	31,166	31,166
Other liabilities	4,759	5,119
Total liabilities	110,650	107,299
Commitments and contingencies (Note 14)
Stockholders’ equity:
Preferred stock, par value of $0.001 per share—25,000,000 shares authorized; nil outstanding as of December 31, 2018 and 2017
Common stock, par value of $0.001 per share—250,000,000 shares authorized; 50,860,588 and 44,167,071 shares issued and outstanding as of December 31, 2018 and 2017, respectively	51	44
Additional paid-in capital	1,639,773	1,221,762
Accumulated other comprehensive loss	(633)	(5,680)
Accumulated deficit	(1,030,283)	(832,672)
Total stockholders’ equity	608,908	383,454
Total liabilities and stockholders’ equity	$ 719,558	$ 490,753

CONSOLIDATED BALANCE SHEETS (Pa

CONSOLIDATED BALANCE SHEETS (Parenthetical) - $ / shares	Dec. 31, 2018	Dec. 31, 2017
Statement Of Financial Position [Abstract]
Preferred stock, par value	$ 0.001	$ 0.001
Preferred stock, shares authorized	25,000,000	25,000,000
Preferred stock, shares outstanding	0	0
Common stock, par value	$ 0.001	$ 0.001
Common stock, shares authorized	250,000,000	250,000,000
Common stock, shares issued	50,860,588	44,167,071
Common stock, shares outstanding	50,860,588	44,167,071

CONSOLIDATED STATEMENTS OF OPER

CONSOLIDATED STATEMENTS OF OPERATIONS - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Revenues:
Total revenues	$ 51,495	$ 2,612	$ 133
Operating expenses:
Cost of sales	1,146	1
Research and development	293,998	231,644	183,204
Selling, general and administrative	127,724	99,909	64,936
Total operating expenses	422,868	331,554	248,140
Loss from operations	(371,373)	(328,942)	(248,007)
Interest income	9,542	4,074	3,789
Gain from sale of priority review vouchers	170,322
Other income (expense)	(5,588)	6,530	(1,621)
Loss before income taxes	(197,097)	(318,338)	(245,839)
Benefit from (provision for) income taxes	(514)	16,199	(35)
Net loss	$ (197,611)	$ (302,139)	$ (245,874)
Net loss per share, basic and diluted	$ (3.97)	$ (7.12)	$ (6.21)
Shares used in computing net loss per share, basic and diluted	49,775,223	42,453,135	39,586,908
Collaboration and License
Revenues:
Total revenues	$ 41,693	$ 2,136
Product Sales
Revenues:
Total revenues	$ 9,802	$ 476	$ 133

CONSOLIDATED STATEMENTS OF COMP

CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Statement Of Income And Comprehensive Income [Abstract]
Net loss	$ (197,611)	$ (302,139)	$ (245,874)
Other comprehensive income (loss):
Foreign currency translation adjustments	(303)	(10,110)	1,322
Transfer of currency translation adjustments balance to other income related to the liquidation of foreign subsidiaries	5,272	3,490
Unrealized gain on available-for-sale securities	78	35	451
Other comprehensive income (loss):	5,047	(6,585)	1,773
Total comprehensive loss	$ (192,564)	$ (308,724)	$ (244,101)

CONSOLIDATED STATEMENTS OF SHAR

CONSOLIDATED STATEMENTS OF SHAREHOLDERS' EQUITY - USD ($) $ in Thousands	Total	Common Stock	Additional Paid-in Capital	Accumulated Other Comprehensive Income (Loss)	Accumulated Deficit
Beginning balance at Dec. 31, 2015	$ 531,090	$ 39	$ 816,578	$ (868)	$ (284,659)
Beginning balance, shares at Dec. 31, 2015		38,882,394
Issuance of common stock in connection with at-the-market offering, net of issuance costs	79,486	$ 1	79,485
Issuance of common stock in connection with at-the-market offering, net of issuance costs, shares		1,159,415
Issuance of common stock in connection with collaboration agreement, net of issuance costs	52,272	$ 1	52,271
Issuance of common stock in connection with collaboration agreement, net of issuance costs, shares		727,120
Put option grant in connection with collaboration agreement	(916)		(916)
Employee stock-based compensation	48,309		48,309
Issuance of common stock under equity plan awards, net of tax	7,834		7,834
Issuance of common stock under equity plan awards, net of tax, shares		471,301
Other comprehensive income (loss)	1,773			1,773
Net loss	(245,874)				(245,874)
Ending balance at Dec. 31, 2016	473,974	$ 41	1,003,561	905	(530,533)
Ending balance, shares at Dec. 31, 2016		41,240,230
Issuance of common stock in connection with at-the-market offering, net of issuance costs	131,960	$ 2	131,958
Issuance of common stock in connection with at-the-market offering, net of issuance costs, shares		2,251,217
Fair value of vested stock options assumed from acquisition	8,979		8,979
Employee stock-based compensation	68,014		68,014
Issuance of common stock under equity plan awards, net of tax	9,251	$ 1	9,250
Issuance of common stock under equity plan awards, net of tax, shares		675,624
Other comprehensive income (loss)	(6,585)			(6,585)
Net loss	(302,139)				(302,139)
Ending balance at Dec. 31, 2017	$ 383,454	$ 44	1,221,762	(5,680)	(832,672)
Ending balance, shares at Dec. 31, 2017	44,167,071	44,167,071
Issuance of common stock in connection with underwrittenpublic offering, net of issuance costs	$ 270,969	$ 5	270,964
Issuance of common stock in connection with underwritten public offering, net of issuance costs, shares		5,043,860
Issuance of common stock in connection with at-the-market offering, net of issuance costs	38,056	$ 1	38,055
Issuance of common stock in connection with at-the-market offering, net of issuance costs, shares		640,257
Employee stock-based compensation	81,165		81,165
Issuance of common stock under equity plan awards, net of tax	27,828	$ 1	27,827
Issuance of common stock under equity plan awards, net of tax, shares		1,009,400
Other comprehensive income (loss)	5,047			5,047
Net loss	(197,611)				(197,611)
Ending balance at Dec. 31, 2018	$ 608,908	$ 51	$ 1,639,773	$ (633)	$ (1,030,283)
Ending balance, shares at Dec. 31, 2018	50,860,588	50,860,588

CONSOLIDATED STATEMENTS OF CASH

CONSOLIDATED STATEMENTS OF CASH FLOWS - USD ($)	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Operating activities:
Net loss	$ (197,611,000)	$ (302,139,000)	$ (245,874,000)
Adjustments to reconcile net loss to net cash used in operating activities:
Stock-based compensation	80,107,000	68,014,000	48,309,000
Amortization of premium (discount) on investment securities, net	(2,641,000)	1,706,000	4,842,000
Depreciation and amortization	19,538,000	5,825,000	3,424,000
Foreign currency remeasurement (gain) loss	5,309,000	(7,018,000)	1,322,000
Gain on sale of priority review voucher	(170,322,000)
Other	(156,000)		700,000
Changes in operating assets and liabilities:
Accounts receivable	(7,583,000)	(5,172,000)
Inventory	(5,283,000)	(757,000)
Prepaid expenses and other current assets	(13,908,000)	2,591,000	(7,147,000)
Other assets	(377,000)	522,000	(1,242,000)
Accounts payable	3,372,000	3,459,000	2,502,000
Accrued liabilities and other liabilities	(1,011,000)	(4,628,000)	32,189,000
Deferred tax liabilities		(16,246,000)
Net cash used in operating activities	(290,566,000)	(253,843,000)	(160,975,000)
Investing activities:
Acquisition, net of cash acquired		(142,804,000)
Purchase of property and equipment	(4,076,000)	(2,793,000)	(10,188,000)
Purchase of investments	(509,796,000)	(230,487,000)	(442,490,000)
Proceeds from sale of investments	7,655,000	157,934,000	140,556,000
Proceeds from maturities of investments	302,564,000	273,632,000	403,239,000
Proceeds from sale of priority review vouchers	170,322,000
Net cash provided by (used in) investing activities	(33,331,000)	55,482,000	91,117,000
Financing activities:
Proceeds from the issuance of common stock in connection with underwritten public offerings, net	270,969,000
Proceeds from the issuance of common stock in connection with at-the-market offering, net	38,056,000	131,960,000	79,486,000
Proceeds from the issuance of common stock in connection with collaboration agreement, net			51,356,000
Proceeds from the issuance of common stock under equity plan awards, net of tax	27,828,000	9,251,000	7,834,000
Repayment of note payable		(4,944,000)
Net cash provided by financing activities	336,853,000	136,267,000	138,676,000
Effect of exchange rate changes on cash	(472,000)	528,000	(65,000)
Net increase (decrease) in cash, cash equivalents, and restricted cash	12,484,000	(61,566,000)	68,753,000
Cash, cash equivalents, and restricted cash at beginning of year	103,041,000	164,607,000	95,854,000
Cash, cash equivalents, and restricted cash at end of year	115,525,000	103,041,000	164,607,000
Supplemental disclosures of non-cash investing and financing information:
Stock-based compensation capitalized into inventory	1,058,000	0	0
Fair value of vested stock options assumed in acquisition		8,979,000
Costs of property and equipment included in accounts payable and accrued liabilities	$ 1,192,000	$ 400,000	147,000
Tenant improvement allowance			$ 3,467,000

Organization and Basis of Prese

Organization and Basis of Presentation	12 Months Ended
	Dec. 31, 2018
Organization Consolidation And Presentation Of Financial Statements [Abstract]
Organization and Basis of Presentation	1. Organization and Basis of Presentation Ultragenyx Pharmaceutical Inc. (the Company) is a biopharmaceutical company incorporated in California on April 22, 2010. The Company subsequently reincorporated in the state of Delaware in June 2011. The Company is focused on the identification, acquisition, development, and commercialization of novel products for the treatment of serious rare and ultra-rare genetic diseases. The Company has two approved therapies. Crysvita ® In addition to the approved treatments for XLH and MPS VII, the Company has four ongoing clinical development programs. Crysvita is being studied for the treatment of tumor induced osteomalacia (TIO), a rare disease that impairs bone mineralization. UX007 is being studied in patients severely affected by long-chain fatty acid oxidation disorders (LC-FAOD), a genetic disorder in which the body is unable to convert long chain fatty acids into energy. The company has two gene therapy pipeline candidates: DTX301 is an adeno-associated virus 8 (AAV8) gene therapy product candidate in development for the treatment of patients with ornithine transcarbamylase (OTC) deficiency, the most common urea cycle disorder; and DTX401 is an AAV8 gene therapy product candidate for the treatment of patients with glycogen storage disease type Ia (GSDIa). The Company operates as one reportable segment. The Company has sustained operating losses and expects such annual losses to continue over the next several years. The Company’s ultimate success depends on the outcome of its research and development and commercialization activities, for which it expects to incur additional losses in the future. Management recognizes the need to raise additional capital to fully implement its business plan. Through December 31, 2018, the Company has relied primarily on the proceeds from equity offerings to finance its operations. The Company intends to raise additional capital through the issuance of equity, borrowings, or strategic alliances with partner companies. However, if such financing is not available at adequate levels, the Company will need to reevaluate its operating plans.

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 Consolidation The consolidated financial statements include the accounts of Ultragenyx Pharmaceutical Inc. and our wholly-owned subsidiaries. All intercompany balances and transactions have been eliminated. Use of Estimates The accompanying consolidated financial statements have been prepared in accordance with U.S. generally accepted accounting principles (“GAAP”). The preparation of the consolidated financial statements in conformity with GAAP requires management to make estimates and assumptions that affect the reported amounts of assets and liabilities, disclosure of contingent liabilities and the reported amounts of expenses in the consolidated financial statements and the accompanying notes. On an ongoing basis, management evaluates its estimates, including those related to clinical trial accruals, fair value of assets and liabilities, income taxes, and stock-based compensation. Management bases its estimates on historical experience and on various other market-specific and relevant assumptions that management believes to be reasonable under the circumstances. Actual results could differ from those estimates. Cash, Cash Equivalents, and Restricted Cash The Company considers all highly liquid investments with original maturities of three months or less from the date of purchase to be cash equivalents. Cash equivalents consist primarily of amounts invested in money market accounts. Restricted cash primarily consists of money market accounts used as collateral for the Company’s obligations under its facility leases. In November 2016, the Financial Accounting Standards Board (FASB) issued Accounting Standards Update (ASU) 2016-18, Statement of Cash Flows (Topic 230): Restricted Cash December 31, 2018 2017 2016 Cash and cash equivalents $ 113,432 $ 100,488 $ 161,120 Restricted cash included in prepaid expenses and other current assets 271 461 1,411 Restricted cash included in other assets 1,822 2,092 2,076 Total cash, cash equivalents, and restricted cash shown in the statements of cash flows $ 115,525 $ 103,041 $ 164,607 Investments All investments have been classified as “available-for-sale” and are carried at estimated fair value as determined based upon quoted market prices or pricing models for similar securities. Management determines the appropriate classification of its investments at the time of purchase and reevaluates such designation as of each balance sheet date. Investments with a maturity of one year or less from the balance sheet date are reported as short-term investments and investments with a maturity of greater than one year from the balance sheet date are reported as long-term investments. Unrealized gains and losses are excluded from earnings and are reported as a component of comprehensive loss. Realized gains and losses and declines in fair value judged to be other than temporary, if any, on available-for-sale securities are included in other income (expense). The cost of securities sold is based on the specific-identification method. Interest on investments is included in interest income. Concentration of Credit Risk and Other Risks and Uncertainties Financial instruments that potentially subject the Company to a concentration of credit risk consist of cash, cash equivalents, and investments. The Company’s cash, cash equivalents, and investments are held by financial institutions that management believes are of high credit quality. The Company’s investment policy limits investments to fixed income securities denominated and payable in U.S. dollars such as U.S. government obligations, money market instruments and funds, corporate bonds, and asset-backed securities and places restrictions on maturities and concentrations by type and issuer. Such deposits may, at times, exceed federally insured limits. The Company has not experienced any losses on its deposits of cash and cash equivalents and its accounts are monitored by management to mitigate risk. The Company is exposed to credit risk in the event of default by the financial institutions holding its cash and cash equivalents, corporate bond issuers, and other financial instruments, to the extent recorded in the balance sheets . The Company has not experienced any credit losses to date from credit risk concentration. Concentration of credit risk with respect to is primarily limited to collaboration partners, drug wholesalers, and retail pharmacy distributors. Credit is extended to our customers based on an evaluation of a customer’s financial condition, and collateral is not The Company is dependent on third-party manufacturers to supply products for research and development activities in its programs. In particular, the Company relies and expects to continue to rely on a small number of manufacturers to supply it with its requirements for the active pharmaceutical ingredients and formulated drugs related to these programs. These programs could be adversely affected by a significant interruption in the supply of active pharmaceutical ingredients and formulated drugs. Inventory The Company values inventory at the lower of cost and net realizable value and determines the cost of inventory using the average-cost method. The Company expenses costs associated with the manufacture of product candidates prior to regulatory approval. Inventories consist of currently approved products. The Company periodically reviews its inventories for excess amounts or obsolescence and writes down obsolete or otherwise unmarketable inventory to its estimated net realizable value. Property and Equipment Property and equipment are stated at cost, less accumulated depreciation and amortization. Depreciation and amortization is computed using the straight-line method over the estimated useful lives of the respective assets. Depreciation and amortization begins at the time the asset is placed in service. Maintenance and repairs are charged to operations as incurred. Upon sale or retirement of assets, the cost and related accumulated depreciation are removed from the balance sheet and the resulting gain or loss, if any, is reflected in operations. The useful lives of property and equipment are as follows: Research and development equipment 5 years Furniture and office equipment 5 years Computer equipment 3 years Software 3-5 years Leasehold improvements Shorter of lease term or estimated useful life Intangible Assets The Company recognizes an acquired intangible apart from goodwill whenever the intangible arises from contractual or other legal rights, or whenever it can be separated or divided from the acquired entity and sold, transferred, licensed, rented or exchanged, either individually or in combination with a related contract, asset or liability. The Company’s intangible assets consist of acquired in-process research and development (IPR&D) and an acquired contract asset. IPR&D assets represent capitalized incomplete research projects that the Company acquired through business combinations. The Company tests its definite and indefinite-lived intangible assets for impairment annually during the fourth quarter and more frequently if events or changes in circumstances indicate that it is more likely than not that the asset is impaired. If it is determined that the asset becomes impaired, the carrying value is written down to its fair value with the related impairment charge recognized in consolidated statements of operations in the period in which the impairment occurs. The Company has not recorded any impairments of intangible assets. Goodwill Goodwill represents the excess of purchase price over fair value of net assets acquired in a business combination and is not amortized. Goodwill is subject to impairment testing at least annually during the fourth quarter or when a triggering event occurs that could indicate a potential impairment. If it is determined that the goodwill becomes impaired, the carrying value is written down to its fair value with the related impairment charge recognized in consolidated statements of operations in the period in which the impairment occurs. The Company has not recorded any impairments of goodwill. Impairment of Long-Lived Assets The Company evaluates its long-lived assets, including property and equipment, for impairment whenever events or changes in circumstances indicate that the carrying value of these assets may not be recoverable. Recoverability of these assets is measured by comparison of the carrying amount of each asset to the future undiscounted cash flows expected to result from the use of the asset and its eventual disposition. If the asset is considered to be impaired, the amount of any impairment is measured as the difference between the carrying value and the fair value of the impaired asset. The Company has not recorded impairment of any long-lived assets. Accruals of Research and Development Costs The Company records accruals for estimated costs of research, preclinical and clinical studies and manufacturing development. These costs are a significant component of the Company’s research and development expenses. A substantial portion of the Company’s ongoing research and development activities are conducted by third-party service providers, including contract research organizations. The Company accrues the costs incurred under its agreements with these third parties based on actual work completed in accordance with agreements established with these third parties. The Company determines the actual costs through discussions with internal personnel and external service providers as to the progress or stage of completion of the services and the agreed-upon fee to be paid for such services. Revenue Recognition Effective January 1, 2017, the Company adopted ASU 2014-09, Revenue from Contracts with Customers (ASC 606) Collaboration and license revenue The Company has certain license and collaboration agreements that are within the scope of Accounting Standards Codification (ASC) 808, Collaborative Agreements provides guidance on the presentation and disclosure of collaborative arrangements. Generally, the classification of the transactions under the collaborative arrangements is determined based on the nature of contractual terms of the arrangement, along with the nature of the operations of the participants. The Company records its share of collaboration revenue, net of transfer pricing related to net sales in the period in which such sales occur, if the Company is considered as an agent in the arrangement. The Company is considered an agent when the collaboration partner controls the product before transfer to the customers and has the ability to direct the use of and obtain substantially all of the remaining benefits from the product. Funding received related to research and development services and commercialization costs are generally classified as a reduction of research and development expenses and selling, general and administrative expenses, respectively, in the consolidated statement of operations, because the provision of such services for collaborative partners are not considered to be part of the Company’s ongoing major or central operations. The also receives royalty revenues under certain of the Company’s license or collaboration agreements in exchange for license of intellectual property. If the Company does not have any future performance obligations for these license or collaboration agreements, royalty revenue is recorded as the underlying sales occur. In to record collaboration revenue, the Company utilizes certain information from its , including revenue from the sale of the product, associated reserves on revenue, and costs incurred for development and sales activities. For the periods covered in the financial statements presented, there have been no significant or material changes to prior period estimates of revenues and expenses. The terms of the Company’s collaboration agreements may contain multiple performance obligations, which may include licenses and research and development activities. The Company evaluates these agreements under ASC 606, Revenue from Contracts with Customers , to determine the distinct performance obligations. The Company analogizes to ASC 606 for the accounting for distinct performance obligations for which there is a customer relationship. Prior to recognizing revenue, the Company makes estimates of the transaction price, including variable consideration that is subject to a constraint. Amounts of variable consideration are included in the transaction price to the extent that it is probable that a significant reversal in the amount of cumulative revenue recognized will not occur and when the uncertainty associated with the variable consideration is subsequently resolved. Total consideration may include nonrefundable upfront license fees, payments for research and development activities, reimbursement of certain third-party costs, payments based upon the achievement of specified milestones, and royalty payments based on product sales derived from the collaboration. If there are multiple distinct performance obligations, the Company allocates the transaction price to each distinct performance obligation based on its relative standalone selling price. The standalone selling price is generally determined based on the prices charged to customers or using expected cost plus margin. The Company estimates the efforts needed to complete the performance obligation and recognizes revenue by measuring the progress towards complete satisfaction of the performance obligation using an input measure. Product sales The Company sells its approved products through a limited number of distributors. Under ASC 606, revenue from product sales is recognized at the point in time when the delivery is made and when title and risk of loss transfers to these distributors. The Company also recognizes revenue from sales of certain products on a “named patient” basis, which are allowed in certain countries prior to the commercial approval of the product. Prior to recognizing revenue, the Company makes estimates of the transaction price, including any variable consideration that is subject to a constraint. Amounts of variable consideration are included in the transaction price to the extent that it is probable that a significant reversal in the amount of cumulative revenue recognized will not occur and when the uncertainty associated with the variable consideration is subsequently resolved. Product sales are recorded net of estimated government-mandated rebates and chargebacks, estimated product returns, and other deductions. Provisions for returns and other adjustments are provided for in the period the related revenue is recorded, as estimated by management. Leases The Company enters into lease agreements for its office and laboratory facilities. These leases are classified as operating leases. Rent expense is recognized on a straight-line basis over the term of the lease and, accordingly, the Company records the difference between cash rent payments and the recognition of rent expense as a deferred rent liability. Incentives granted under the Company’s facilities leases, including allowances to fund leasehold improvements, are deferred and are recognized as adjustments to rental expense on a straight-line basis over the term of the lease. Comprehensive Loss Comprehensive loss is the change in stockholders’ equity from transactions and other events and circumstances other than those resulting from investments by stockholders and distributions to stockholders. The Company’s other comprehensive loss is comprised of unrealized gains and losses on investments in available-for-sale securities and foreign currency translation adjustments. Research and Development Research and development costs are expensed as incurred and consist of salaries and benefits, stock-based compensation expense, lab supplies and facility costs, as well as fees paid to other nonemployees and entities that conduct certain research and development activities on the Company’s behalf. Amounts incurred in connection with license agreements are also included in research and development expense. Nonrefundable advance payments for goods or services to be received in the future for use in research and development activities are deferred. The deferred amounts are expensed as the related goods are delivered or the services are performed. Stock-Based Compensation Stock-based awards issued to employees, including stock options, restricted stock units (RSUs), and performance stock units (PSUs) are recorded at fair value as of the grant date and recognized as expense on a straight-line basis over the employee’s requisite service period (generally the vesting period). PSUs vest only if certain specified criteria are achieved and the employees’ continued service requirements are met; therefore, the expense recognition occurs when the likelihood of the PSUs being earned is deemed probable. Stock compensation expense on awards expected to vest are recognized net of estimated forfeitures. Income Taxes The Company uses the liability method of accounting for income taxes. Under this method, deferred tax assets and liabilities are determined based on the differences between the financial reporting and the tax bases of assets and liabilities and are measured using the enacted tax rates and laws that will be in effect when the differences are expected to reverse. The Company must then assess the likelihood that the resulting deferred tax assets will be realized. A valuation allowance is provided when it is more likely than not that some portion or all of a deferred tax asset will not be realized. Due to the Company’s lack of earnings history, the net deferred tax assets have been fully offset by a valuation allowance. In conjunction with Dimension acquisition, a deferred tax liability was recorded reflecting the tax impact of the difference between the book basis and tax basis of acquired IPR&D. Such deferred income tax liability is not used to offset deferred tax assets when analyzing the Company’s valuation allowance as the acquired IPR&D is considered to have an indefinite life until the Company completes or abandons development of the acquired IPR&D. The Company recognizes benefits of uncertain tax positions if it is more likely than not that such positions will be sustained upon examination based solely on their technical merits, as the largest amount of benefit that is more likely than not to be realized upon the ultimate settlement. The Company’s policy is to recognize interest and penalties related to the underpayment of income taxes as a component of income tax expense or benefit. To date, there have been no interest or penalties charged in relation to the unrecognized tax benefits. Foreign Currency Assets and liabilities of non-U.S. subsidiaries that operate in a local currency environment, where the local currency is the functional currency, are translated to U.S. dollars at exchange rates in effect at the balance sheet date, with the resulting translation adjustments directly recorded to a separate component of accumulated other comprehensive loss. Income and expense accounts are translated at average exchange rates for the period. Transactions which are not in the functional currency of the entity are remeasured into the functional currency and gains or losses resulting from the remeasurement recorded in other income (expense). Net Loss per Share Basic net loss per share is calculated by dividing the net loss by the weighted-average number of shares of common stock outstanding during the period, without consideration for common stock equivalents. Diluted net loss per share is the same as basic net loss per share, since the effects of potentially dilutive securities are antidilutive. In periods when we have incurred a net loss, options and warrants to purchase common stock are considered common stock equivalents, but have been excluded from the calculation of diluted net loss per share, as their effect is antidilutive. Business Combinations The Company applies the provisions of ASC 805, “Business Combinations” allocates Recent Accounting Pronouncements In February 2016, the FASB issued ASU No. 2016-02, Leases (Topic 842) As of January 1, 2019, the Company expects to record a right-to-use asset in the range of $15.0 million to $18.4 million, short-term lease liability in the range of $4.1 million to $5.0 million, and long-term lease liability in the range of $15.7 million to $19.2 million and no adjustment to the retained earnings. The Company is continuing to evaluate the effect that this guidance will have on its Consolidated Financial Statements and related disclosures.

Dimension Acquisition

Dimension Acquisition	12 Months Ended
	Dec. 31, 2018
Business Combinations [Abstract]
Dimension Acquisition	3. Dimension Acquisition On November 7 Cash payments $ 152,292 Fair value of vested stock options assumed 8,979 REGENX termination fee 2,850 Fair value of total consideration $ 164,121 The following table summarizes the fair values of assets acquired and liabilities assumed as of the date of acquisition (in thousands): Cash and cash equivalents $ 12,338 Short-term investments 9,737 Other current assets 11,155 Property and equipment 6,580 In-process research and development 129,000 Bayer collaboration agreement 13,526 Accounts payable and accrued liabilities (10,265 ) Notes payable (4,944 ) Deferred tax liabilities (47,412 ) Net identifiable net assets acquired 119,715 Goodwill 44,406 Net assets acquired $ 164,121 The transaction was accounted for as a business combination under the acquisition method of accounting as outlined in ASC 805, Business Combinations The Company recorded $47.4 million in non-current deferred tax liability resulting from the acquisition reflecting the tax impact of the difference between the book basis and tax basis of acquired IPR&D. Such deferred income tax liability is not used to offset deferred tax assets when analyzing the Company’s valuation allowance as the acquired IPR&D is considered to have an indefinite life until the Company completes or abandons development of the acquired IPR&D. Subsequent to the acquisition date, the deferred tax liability was reduced to $31.2 million due to the reduction of U.S. corporate tax rate from 34% to 21% in December 2017. The goodwill balance is primarily attributed to the deferred tax liabilities arising from the temporary differences on IPR&D assets between book and tax basis as well as the relating to the assembled workforce and expanded market opportunities when integrating Dimension’s research with the Company. The goodwill balance is not deductible for U.S. income tax purposes. The assumed notes payable of $4.9 million, along with the outstanding interest was repaid in December 2017. In connection with the acquisition, the Company recognized transaction costs of $6.0 million as selling, general and administrative expense. There were no purchase price adjustments subsequent to the acquisition. Pro Forma Financial Information The Company's consolidated statement of operations from November 7, 2017 through December 31, 2017 includes Dimension total revenue of $2.1 million and a net loss of $7.5 million. The following supplemental unaudited pro forma information presents the financial results as if the acquisition had occurred on January 1, 2016 (in thousands): For the year ended December 31, 2017 2016 Total revenues $ 18,528 $ 12,684 Net loss 341,737 306,596 The unaudited pro forma financial information include pro forma adjustments that assume the acquisition occurred on January 1, 2016. These items include adjustments to remove the impact of transaction costs related to the acquisition of $9.6 million for the year ended December 31, 2017 and to record the amortization of definite-lived intangible assets of $1.8 million and $11.1 million for the years ended December 31, 2017 and 2016, respectively. Other adjustments include reduction of interest income, amounts related to severance of certain employees, acceleration of certain equity awards, and adjustments to conform to the Company’s accounting policies on revenue. These unaudited pro forma results are presented for informational purposes only and are not necessarily indicative of what the actual results of operations of the combined company would have been if the acquisition had occurred at the beginning of the period presented, nor are they indicative of future results of operations.

Fair Value Measurements

Fair Value Measurements	12 Months Ended
	Dec. 31, 2018
Fair Value Disclosures [Abstract]
Fair Value Measurements	4. Fair Value Measurements Financial assets and liabilities are recorded at fair value. The carrying amount of certain financial instruments, including cash and cash equivalents, accounts receivable, accounts payable and accrued liabilities approximate fair value due to their relatively short maturities. Assets and liabilities recorded at fair value on a recurring basis in the balance sheets are categorized based upon the level of judgment associated with the inputs used to measure their fair values. Fair value is defined as the exchange price that would be received for an asset or an exit price that would be paid to transfer a liability in the principal or most advantageous market for the asset or liability in an orderly transaction between market participants on the measurement date. The authoritative guidance on fair value measurements establishes a three-tier fair value hierarchy for disclosure of fair value measurements as follows: Level 1 —Inputs are unadjusted, quoted prices in active markets for identical assets or liabilities at the measurement date; Level 2 —Inputs are observable, unadjusted quoted prices in active markets for similar assets or liabilities, unadjusted quoted prices for identical or similar assets or liabilities in markets that are not active, or other inputs that are observable or can be corroborated by observable market data for substantially the full term of the related assets or liabilities; and Level 3 —Unobservable inputs that are significant to the measurement of the fair value of the assets or liabilities that are supported by little or no market data. The Company’s financial instruments consist of Level 1 and Level 2 assets. Where quoted prices are available in an active market, securities are classified as Level 1. Money market funds are classified as Level 1. Level 2 assets consist primarily of corporate bonds, asset backed securities, commercial paper and U.S. Government agency securities based upon quoted market prices for similar movements in active markets, quoted prices for identical or similar instruments in markets that are not active and model-based valuation techniques for which all significant inputs are observable in the market or can be corroborated by observable market data for substantially the full term of the assets. Where applicable these models project future cash flows and discount the future amounts to a present value using market-based observable inputs obtained from various third party data providers, including but not limited to, benchmark yields, interest rate curves, reported trades, broker/dealer quotes and reference data. The following table sets forth the fair value of the Company’s financial assets and liabilities remeasured on a recurring basis based on the three-tier fair value hierarchy (in thousands): December 31, 2018 Gross Unrealized Fair Value Hierarchy Amortized Cost Gains Losses Estimated Fair Value Money market funds Level 1 $ 72,999 $ — $ — $ 72,999 Time deposits Level 2 10,000 — — 10,000 Corporate bonds Level 2 180,167 — (241 ) 179,926 Commercial paper Level 2 50,198 — — 50,198 Asset-backed securities Level 2 22,597 — (10 ) 22,587 U.S. Government Treasury and agency securities Level 2 99,087 2 (55 ) 99,034 Total $ 435,048 $ 2 $ (306 ) $ 434,744 December 31, 2017 Gross Unrealized Fair Value Hierarchy Amortized Cost Gains Losses Estimated Fair Value Money market funds Level 1 $ 79,670 $ — $ — $ 79,670 Corporate bonds Level 2 39,330 — (90 ) 39,240 U.S. Government Treasury and agency securities Level 2 105,031 — (292 ) 104,739 Total $ 224,031 $ — $ (382 ) $ 223,649 At December 31, 2018, the remaining contractual maturities of available-for-sale securities were less than one year. There have been no significant realized gains or losses on available-for-sale securities for the periods presented. All marketable securities with unrealized losses at December 31, 2018 have been in a loss position for less than twelve months or the loss is not material and were temporary in nature. We do not intend to sell the investments that are in an unrealized loss position before recovery of their amortized cost basis.

Balance Sheet Components

Balance Sheet Components	12 Months Ended
	Dec. 31, 2018
Investments Debt And Equity Securities [Abstract]
Balance Sheet Components	5. Balance Sheet Components Inventory Inventory consists of the following (in thousands): December 31, 2018 2017 Work-in-process $ 5,384 $ 737 Finished goods 1,681 20 Total inventory $ 7,065 $ 757 Property and Equipment, net Property and equipment, net consists of the following (in thousands): December 31, 2018 2017 Leasehold improvements $ 15,705 $ 15,085 Research and development equipment 9,856 7,696 Furniture and office equipment 3,379 2,873 Computer equipment and software 7,342 6,745 Construction-in-progress 1,970 429 Property and equipment, gross 38,252 32,828 Less accumulated depreciation (18,206 ) (10,991 ) Property and equipment, net $ 20,046 $ 21,837 Depreciation expense for the years ended December 31, 2018, 2017 and 2016 was $7.2 million, $4.8 million and $3.4 million respectively. Amortization of leasehold improvements and software is included in depreciation expense. Accrued Liabilities Accrued liabilities consists of the following (in thousands): December 31, 2018 2017 Research, clinical study, and manufacturing expenses $ 16,912 $ 17,141 Payroll and related expenses 36,443 26,527 Repayment liability under collaboration agreement — 3,681 Contract liability — 5,986 Other 9,095 8,793 Total accrued liabilities $ 62,450 $ 62,128

Intangible Assets, Net

Intangible Assets, Net	12 Months Ended
	Dec. 31, 2018
Intangible Assets Net Excluding Goodwill [Abstract]
Intangible Assets, Net	6. Intangible Assets, net In connection with the acquisition as described in Note 3 “Dimension Acquisition" the Company recognized IPR&D assets of $129.0 million and a contract asset of $13.5 million. The estimated fair value of these intangible assets was measured using Level 3 inputs as of the acquisition date IPR&D assets represent the fair value of acquired programs to develop an AAV gene therapy for OTC deficiency and to develop an AAV gene therapy for glycogen storage disease type Ia. The fair value of IPR&D assets acquired was determined based on the discounted present value of each research project’s projected cash flows using an income approach, including the application of probability factors related to the likelihood of success of the program reaching final development and commercialization. Additionally, the projections consider the relevant market sizes and growth factors, estimated future cash flows from product sales resulting from completed products and in-process projects and timing and costs to complete the in-process projects. The rates utilized to discount the net cash flows to their present value are commensurate with the stage of development of the projects and uncertainties in the economic estimates used in the projections. IPR&D assets are considered to be indefinite-life until the completion or abandonment of the associated research and development efforts The contract asset represents the fair value of the agreement with Bayer HealthCare LLC to research, develop, and commercialize AAV gene therapy products for treatment of hemophilia A. The fair value of the contract asset was determined based on the discounted present value of the estimated net future income and is being amortized to research and development expense over the research term which is expected to be complete in 2019. The Company recorded research and development expense of $12.3 million and $1.0 million for the years ended December 31, 2018 and 2017, respectively, related to the amortization of the asset. As of December 31, 2018, the remaining value of the contract asset is $0.2 million and the estimated future amortization expense associated with the contract asset is $0.2 million in 2019. The Company tests the intangible assets for impairment annually during its fourth quarter. No impairment charges have been recognized on intangible assets.

Revenue

Revenue	12 Months Ended
	Dec. 31, 2018
Revenue From Contract With Customer [Abstract]
Revenue	7. Revenue The following table disaggregates total revenues from external customers by collaboration and license revenue and product sales (in thousands): Year Ended December 31, 2018 2017 2016 Collaboration and license revenue: KHK (Crysvita) $ 18,226 $ 9 $ — Bayer 23,467 2,127 — Total collaboration and license revenue 41,693 2,136 — Product sales: Crysvita 644 — — Mepsevii 7,903 476 133 UX007 1,255 — — Total product sales 9,802 476 133 Total revenues $ 51,495 $ 2,612 $ 133 The following table disaggregates total revenues based on geographic location (in thousands): Year Ended December 31, 2018 2017 2016 United States $ 45,339 $ 2,289 $ — Europe 5,293 323 133 All other 863 — — Total revenues $ 51,495 $ 2,612 $ 133 The following table presents the activity and ending balances for sales-related accruals and allowances (in thousands): Product sales reserves December 31, 2016 $ — Provisions 41 December 31, 2017 41 Provisions 2,466 Payments and adjustments (1,267 ) December 31, 2018 $ 1,240 The following table presents changes in the contract assets (liabilities) for the years ended December 31, 2018 and 2017 (in thousands): December 31, 2018 2017 Balance of contract assets (liabilities) at beginning of year $ (5,986 ) $ — Contract liability assumed at acquisition — (2,526 ) Additions 24,055 4,658 Deductions (15,090 ) (8,118 ) Balance of contract assets (liabilities) at end of year $ 2,979 $ (5,986 ) The Company’s largest accounts receivable balance was 88% of the December 31, 2018 total accounts receivable balance and was due from a collaboration partner, as compared to 97% as of December 31, 2017 for a different collaboration partner

License and Research Agreements

License and Research Agreements	12 Months Ended
	Dec. 31, 2018
Research Grant Agreement [Abstract]
License and Research Agreements	8. License and Research Agreements Kyowa Hakko Kirin Collaboration and License Agreement In August 2013, the Company entered into a collaboration and license agreement with Kyowa Hakko Kirin Co., Ltd. (KHK). Under the terms of this collaboration and license agreement, as amended, the Company and KHK will collaborate on the development and commercialization of Crysvita in the field of orphan diseases in the United States and Canada, or the profit share territory, and in the European Union and Switzerland, or the European territory, and the Company will have the right to develop and commercialize such products in the field of orphan diseases in Mexico and Central and South America, or Latin America. In the field of orphan diseases, and except for ongoing studies being conducted by KHK, the Company will be the lead party for development activities in the profit share territory and in the European territory until the applicable transition dates; the Company will also be the lead party for core development activities conducted in Japan and Korea, for which the core development plan is limited to clinical trials mutually agreed to by the Company and KHK. The Company will share the costs for development activities in the profit share territory and the European territory conducted pursuant to the development plan before the applicable transition date equally with KHK, and KHK shall be responsible for 100% of the costs for development activities in Japan and Korea. On the applicable transition dates in the profit share territory and the European territory, KHK will become the lead party and be responsible for the costs of the development activities. However, the Company will continue to share the costs of the studies commenced prior to the applicable transition date equally with KHK. Crysvita was approved in the European Union in February 2018 and was approved by the FDA in April 2018. The collaboration and license agreements are within the scope of ASC 808, which provides guidance on the presentation and disclosure of collaborative arrangements. Collaboration revenue related to sales in profit share territory The Company and KHK share commercial responsibilities and profits in the profit share territory until the applicable transition date. Under the collaboration agreement, KHK will manufacture and supply Crysvita for commercial use in the profit share territory. The remaining profit or loss after supply costs from commercializing products in the profit-share territory, until the applicable transition date, are shared between the Company and KHK on a 50/50 basis. Thereafter, the Company will be entitled to receive a tiered double-digit revenue share in the mid-to-high 20% range. The Company is considered the agent in the profit share territory as KHK controls the product before transfer to the customers and has the ability to direct the use of and obtain substantially all of the remaining benefits from the product. The Company recognizes a pro-rata share of collaboration revenue, net of supply costs, in the period the sale occurs. The Company concluded that its portion of KHK’s sales in the profit share territory is analogous to a royalty and therefore recorded $15.3 million as collaboration revenue, similar to a royalty, during the year ended December 31, 2018. Royalty revenue related to sales in European territory KHK has the commercial responsibility for in the European territory. The Company receives a royalty of up to 10% on net sales in the European territory, which is recognized as the underlying sales occur. The Company’s Year Ended December 31, 2018 2017 2016 Company's share of collaboration revenue in profit share territory $ 15,334 $ — $ — Royalty revenue in European territory 2,892 9 — Total $ 18,226 $ 9 $ — Product revenue related to sales in other territories The Company is responsible for commercializing in Latin America. The Company is considered the principal in the arrangement as the Company controls the product before it is transferred to the customer. Accordingly, the Company records revenue on a gross basis related to the sale of once the product is delivered and the risk and title of the product is transferred to the distributor. For the year ended December 31, 2018, the Company recorded product sales of $0.6 million, net of estimated product returns and other deductions. Under KHK manufactures and supplies for sales in the Latin America territory. The Company also pays to KHK a low single-digit royalty on net sales. In May 2017, the Company signed an agreement with a wholly-owned subsidiary of KHK pursuant to which the Company was granted the right to commercialize Crysvita in Turkey. KHK’s subsidiary has the option to assume responsibility for commercialization efforts from the Company, after a certain minimum period. The Company is considered the principal in the arrangement as the Company controls the product before it is transferred to the customer; accordingly, the Company will record revenue on a gross basis for sales made in Turkey, including named patient sales, until KHK’s subsidiary assumes responsibility for commercialization efforts. Cost sharing payments Under the collaboration agreement, KHK and the Company share certain development and commercialization costs. Year Ended December 31, 2018 2017 2016 Research and development $ 32,240 $ 31,165 $ 25,356 Selling, general and administrative 14,228 4,466 1,532 Total $ 46,468 $ 35,631 $ 26,888 Collaboration receivable The Company had accounts receivable from KHK in the amount of $11.2 million and $9 thousand, from profit share revenue and royalties, and other receivables recorded in prepaid and other current assets of $11.1 million and $10.3 million from commercial and development activity reimbursements, as of December 31, 2018 and December 31, 2017, respectively. Saint Louis University License Agreement In November 2010, the Company entered into a license agreement with Saint Louis University (SLU). Under the terms of this license agreement, SLU granted the Company an exclusive worldwide license to make, have made, use, import, offer for sale, and sell therapeutics related to SLU’s beta-glucuronidase product for use in the treatment of human diseases. The Company made a milestone payment of $0.1 million upon approval of Mepsevii for treatment of MPS 7. The Company is required to pay to SLU a low single-digit royalty on net sales of the licensed products in any country or region, upon reaching a certain level of cumulative worldwide sales of the product. Baylor Research Institute License Agreement In September 2012, the Company entered into a license agreement with Baylor Research Institute (BRI). Under the terms of this license agreement, BRI exclusively licensed to the Company its territories for certain intellectual property related to triheptanoin (UX007). The Company may make future payments of up to $5.3 million contingent upon attainment of various development milestones relating to the development of LC-FAOD and $7.5 million contingent upon attainment of various sales milestones. Additionally, the Company will pay to BRI a mid-single digit royalty on net sales of the licensed product in the licensed territories, if such product sales are ever achieved. REGENXBIO, Inc. The Company has a license agreement with REGENX, for an exclusive, sublicensable, worldwide commercial license under certain intellectual property for preclinical and clinical research and development, and commercialization of drug therapies using REGENX 's licensed patents for the treatment of hemophilia A, OTC deficiency, GSD1a, and one other preclinical indication. The Company will pay an annual fee and certain milestone fees per disease indication, low to mid single-digit royalty percentages on net sales of licensed products, and milestone and sublicense fees owed by REGENX to its licensors, contingent upon the attainment of certain development activities as outlined in the agreement. The Company also has an option and license agreement with REGENX fee of $0.1 million Bayer HealthCare LLC The Company has an agreement with Bayer Healthcare LLC (Bayer) to research, develop and commercialize AAV gene therapy products for treatment of hemophilia A (DTX 201). Under this agreement, Bayer has been granted an exclusive license to develop and commercialize one or more novel gene therapies for hemophilia A. The Company is responsible for the development of DTX201 under the agreement through a proof-of-concept (POC) clinical trial, in accordance with the mutually agreed upon research budget. Upon the successful demonstration of clinical POC, the agreement requires that Bayer use commercially reasonable efforts to manage and fund any subsequent clinical trials and commercialization of gene therapy products for treatment of hemophilia A. Bayer will have worldwide rights to commercialize the potential future product. Bayer is responsible to fund certain research and development services performed by the Company in the performance of its obligations under the annual research plan and budget. Under the terms of the agreement with Bayer, the Company is eligible to receive development and commercialization milestone payments of up to $232.0 million, as well as, royalty payments ranging in the high single-digit to low double-digit percentages, not exceeding the mid-teens, of net sales of licensed products. The Company achieved the first milestone in December 2017, the second milestone in April 2018, and has received $15.0 million for such milestones to date. As of the acquisition date of Dimension on November 7, 2017, the Company valued the contract under ASC 805 and recorded an intangible asset of $13.5 million. The intangible asset is being amortized to research and development expense over the research term which is expected to be complete in 2019. The Company recorded research and development expense of $12.3 million and $1.0 million for the years ended December 31, 2018 and 2017, respectively, for the amortization of the intangible asset. The Company evaluated the agreement under ASC 606 and recorded a contract liability as of November 7, 2017 of $2.5 million. It was determined that the performance obligations under the agreement includes (i) research and development services to be provided over the research term, (ii) a development and commercialization license, and (iii) the Company’s participation in certain committees. It was determined that these performance obligations are not distinct in the context of the contract and therefore are a single performance obligation. The Company calculated the transaction price by including the unconstrained milestones along with the estimated payments for research and development services and recorded $23.5 million and $2.1 million as collaboration and license revenue for the years ended December 31, 2018 and 2017, respectively, by measuring the progress toward complete satisfaction of the performance obligation using an input measure. The performance obligation under the contract is expected to be substantially complete by end of 2019. As of December 31, 2018 and 2017, the Company had a $3.0 million contract asset and a $5.4 million contract liability associated with the performance obligation, respectively. University of Pennsylvania The Company has an agreement with University of Pennsylvania School of Medicine (Penn) to sponsor certain research related to liver and hemophilia gene therapy. In consideration for funding such research, Penn granted the Company an option to obtain a worldwide, non-exclusive or exclusive, royalty-bearing license, with the right to sublicense, under certain patent rights conceived, created or reduced to practice in the conduct of the research. The Company is required to reimburse Penn for filing, prosecuting and maintaining such patent rights unless and until the Company declines to exercise its option. Penn provides the Company with task-based, scientific reports of progress and results of the research, and granted the Company a royalty-free, nontransferable, non-exclusive right to copy and distribute any research reports furnished to the Company for any reasonable purpose, provided the results are not made publicly available until certain conditions are met, and the right to use, disclose and otherwise exploit the research results for any reasonable purpose, subject to similar restrictions on our public disclosure of the research results. Otherwise, the sponsored research agreement contains customary confidentiality provisions. The Company also has a research, collaboration, and license agreement with Penn, which provides the terms for the Company and Penn to collaborate with respect to the pre-clinical development of gene therapy products for the treatment of certain indications. Under the agreement, Penn granted the Company an exclusive, worldwide license to certain patent rights arising out of the research program, subject to certain retained rights, and a non-exclusive, worldwide license to certain Penn intellectual property, in each case to research, develop, make, have made, use, sell, offer for sale, commercialize and import licensed products in each indication for the term of the agreement. The Company will fund the cost of the research program in accordance with a mutually agreed-upon research budget and will be responsible for clinical development, manufacturing and commercialization of each indication. The Company will make milestone payments of up to $5.0 million for each indication, if certain development milestones are achieved over time, as well as low to mid-single digit royalties on net sales of each licensed product. The Company will also make milestone payments of up to $25.0 million per approved product if certain commercial milestones are achieved. Takeda License and Collaboration and Purchase Agreements In June 2016, the Company executed a collaboration and license agreement with Takeda Pharmaceutical Company Limited (Takeda). Pursuant to the agreement, which became effective in July 2016, the Company obtained an exclusive license for a pre-clinical compound from Takeda in a pre-determined field of use. The Company was responsible for the development costs for the pre-clinical compound and the identified option product pursuant to the initial development plan which was completed as of June 30, 2018. A significant portion of the work under the initial development plan was performed by Takeda, and as a result, the Company paid $10.6 million to Takeda for performance of their services. The Company concluded that the payments to Takeda were not in return for a distinct service that Takeda had transferred to the Company; therefore, the payments made to Takeda were accounted for as a reduction in the total transaction price of $14.3 million. The remaining $3.7 million of the transaction price was allocated to the distinct performance obligations on a relative standalone selling price basis. The Company recorded $1.2 million and $2.5 million for the years ended December 31, 2018 and 2017, respectively, as a reduction of research and development expenses by measuring the progress toward complete satisfaction of the individual performance obligation using an input measure. Costs incurred by the Company associated with co-development activities performed under this collaboration are included in research and development expense in the accompanying consolidated statements of operations. The Company had no repayment liability as of December 31, 2018, a $3.7 million repayment liability as of December 31, 2017, no contract liability as of December 31, 2018, and a $0.6 million contract liability as of December 31, 2017. Arcturus Research Collaboration and License Agreement In October 2015, the Company entered into a Research Collaboration and License Agreement with Arcturus Therapeutics, Inc. (Arcturus). The Company and Arcturus are collaborating on the research and development of therapies for select rare diseases. As consideration for entering into the arrangement, the Company paid Arcturus an upfront fee of $10.0 million. Arcturus has the primary responsibility for conducting certain research services, funded by the Company, and the Company will be responsible for development and commercialization costs.

Gain from Sale of Priority Revi

Gain from Sale of Priority Review Vouchers	12 Months Ended
	Dec. 31, 2018
Goodwill And Intangible Assets Disclosure [Abstract]
Gain from Sale of Priority Review Vouchers	9. Gain from Sale of Priority Review Vouchers In January 2018, the Company completed the sale of a Rare Pediatric Disease Priority Review Voucher (PRV) it received in connection with the approval of Mepsevii for $130.0 million. In June 2018, the Company also completed the sale of the PRV it received in connection with the approval of Crysvita for $80.6 million, net, which was shared equally with KHK. As the PRVs did not have a carrying value, the gain recognized was equal to the net proceeds received. The Company recorded $170.3 million for its portion of the net proceeds for the year ended December 31, 2018 as a gain from the sale of the priority review vouchers.

Equity

Equity	12 Months Ended
	Dec. 31, 2018
Equity [Abstract]
Equity	10. Equity At-the-Market Offerings In July 2016, the Company entered into an At-The-Market (ATM) sales agreement with Cowen and Company, LLC (Cowen), whereby the Company sold $150.0 million in aggregate proceeds of common stock, through Cowen as our sales agent. During the years ended December 31, 2017 and 2016, the Company sold 912,351 and 1,159,415 shares of common stock, resulting in net proceeds of approximately $67.6 million and $79.5 million, respectively, after commissions and other offering costs. In July 2017, the Company entered into an additional ATM sales agreement with Cowen whereby the Company may sell up to $150.0 million in aggregate proceeds of common stock from time to time, through Cowen as its sales agent. During the years ended December 31, 2018 and 2017, the Company sold 640,257 and 1,338,866 shares of common stock, respectively, resulting in net proceeds of approximately $38.1 million and $64.3 million, respectively, after commissions and other offering costs. Subsequent to December 31, 2018, the Company sold an additional 379,707 shares of common stock resulting in net proceeds of $19.3 million, after commissions and offering costs. Underwritten Public Offering In January 2018, the Company completed an underwritten public offering in which 5,043,860 shares of common stock were sold, which includes 657,895 shares purchased by the underwriters pursuant to an option granted to them in connection with the offering, at a public offering price of $57.00 per share. The total proceeds that the Company received from the offering were approximately $271.0 million, net of underwriting discounts and commissions. Common Stock Warrants As of December 31, 2018 and 2017, there was an aggregate of 149,700 and expiration dates in 2020 and 2021.

Stock-Based Awards

Stock-Based Awards	12 Months Ended
	Dec. 31, 2018
Disclosure Of Compensation Related Costs Sharebased Payments [Abstract]
Stock-Based Awards	11. Stock-Based Awards Equity Plan Awards In 2011, the Company adopted the 2011 Equity Incentive Plan (the 2011 Plan). The 2011 Plan provides for the granting of stock-based awards to employees, directors, and consultants under terms and provisions established by the board of directors. In 2014, the Company adopted the 2014 Incentive Plan (the 2014 Plan). The 2014 Plan had 2,250,000 shares of common stock available for future issuance at the time of its inception, which included 655,038 shares available under the 2011 Plan, which were transferred to the 2014 Plan upon adoption. No further grants subsequent to the IPO were made under the 2011 Plan. The 2014 Plan provides for automatic annual increases in shares available for grant, beginning on January 1, 2015 through January 1, 2024. Under the terms of the 2014 Plan, awards may be granted at an exercise price not less than fair market value. For employees holding more than 10% of the voting rights of all classes of stock, the exercise prices for awards must be at least 110% of fair market of the common stock on the grant date, as determined by the board of directors. The term of an award granted under the 2014 Plan may not exceed ten years. Typically, the vesting schedule for option grants to the employees provides that 1/4 of the grant vests upon the first anniversary of the date of grant, with the remainder of the shares vesting monthly thereafter at a rate of 1/48 of the total shares subject to the option. The vesting schedule for RSU grants provides that 1/4 of the grant vests upon the annual anniversary of the date of grant over the period of four years. As part of the acquisition of Dimension (discussed in Note 3 “Dimension Acquisition”), the Company assumed an equivalent 639,897 options to purchase shares of common stock of the Company from the equity plans of Dimension. No further grants subsequent to the acquisition are available under these equity plans. As of December 31, 2018, an aggregate of 8,845,990 shares of common stock have been authorized for issuance under the 2011 Plan, the 2014 Plan, and the assumed equity awards from the Dimension plans. Stock Option Activity The following table summarizes activity under the Company’s stock option plans, including the 2011 Plan, the 2014 Plan, the assumed equity awards from the Dimension plans and related information: Options Outstanding Number of Options Weighted- Average Exercise Weighted-Average Remaining Contractual Term Aggregate Intrinsic Value (In Outstanding — December 31, 2015 3,826,963 $ 56.36 8.58 $ 217,386 Options granted 1,435,995 67.00 Options exercised (425,922 ) 21.21 Options cancelled (407,564 ) 70.87 Outstanding — December 31, 2016 4,429,472 $ 61.85 8.22 $ 79,135 Options granted 1,328,860 71.99 Options assumed 639,897 27.97 Options exercised (478,470 ) 16.25 Options cancelled (520,349 ) 78.70 Outstanding — December 31, 2017 5,399,410 $ 62.75 7.40 $ 37,687 Options granted 1,479,451 55.54 Options exercised (713,263 ) 36.21 Options cancelled (812,474 ) 74.80 Outstanding — December 31, 2018 5,353,124 $ 62.46 7.22 $ 23,243 Vested and exercisable — December 31, 2018 2,870,804 $ 62.10 6.09 $ 22,555 Vested and expected to vest — December 31, 2018 5,134,594 $ 62.53 7.16 $ 23,191 The aggregate intrinsic values of options outstanding, vested and exercisable, and vested and expected to vest were calculated as the difference between the exercise price of the options and the fair value of the Company’s common stock. The total intrinsic value of options exercised during the years ended December 31, 2018, 2017, and 2016 was $22.9 million, $20.4 million and $22.2 million, respectively. Cash received from the exercise of options was $25.8 The weighted-average estimated fair value of stock options granted was $33.32, $44.20 and $40.49 per share of the Company’s common stock during the years ended December 31, 2018, 2017, and 2016, respectively. The total estimated grant date fair value of options vested during the years ended December 31, 2018, 2017, and 2016 was $51.7 million, $49.1 million, and $43.8 million, respectively. Restricted Stock Units The following table summarizes activity under the Company’s Restricted Stock Units (RSUs) from the 2014 Plan and related information: RSUs Outstanding Number of Shares Weighted- Average Grant Date Fair Value Unvested — December 31, 2015 197,151 $ 87.24 RSUs granted 477,816 66.83 RSUs released (52,273 ) 82.59 RSUs cancelled (48,950 ) 78.04 Unvested — December 31, 2016 573,744 $ 71.45 RSUs granted 516,161 71.58 RSUs released (156,021 ) 71.93 RSUs cancelled (112,324 ) 76.78 Unvested — December 31, 2017 821,560 $ 70.71 RSUs granted 555,905 56.01 RSUs released (235,913 ) 71.01 RSUs cancelled (187,475 ) 65.37 Unvested — December 31, 2018 954,077 $ 63.12 The fair value of the RSUs is determined on the grant date based on the fair value of the Company’s common stock. The fair value of the RSUs is recognized as expense ratably over the vesting period of one to four years. The total grant date fair value of the 235,913 shares vested during 2018 was approximately $16.8 million with an aggregate intrinsic value of the shares of $14.9 million. Performance Stock Units In December 2017, the Company began granting performance stock units (PSUs) to certain employees. The following table summarizes activity under the Company’s PSUs from the 2014 Plan and related information: PSUs Outstanding Number of Shares Weighted- Average Grant Date Fair Value Unvested — December 31, 2016 — $ — PSUs granted 508,850 48.03 Unvested — December 31, 2017 508,850 $ 48.03 PSUs granted 71,725 59.67 PSUs cancelled (97,375 ) 48.58 Unvested — December 31, 2018 483,200 $ 49.65 These PSUs are subject to vest only if certain specified criteria are achieved and the employees’ continued service with the Company after achievement of the specified criteria. As of December 31, 2018, the specified criteria were deemed probable of achievement or already achieved. Stock-based compensation for these PSUs is recognized over the service period beginning in the period the Company determines it is probable that the performance criteria will be achieved. Employee Stock Purchase Plan In January 2014, the Company adopted the 2014 Employee Stock Purchase Plan (ESPP) and reserved a total of 600,000 shares of common stock for issuance under the ESPP. The ESPP provides for automatic annual increases in shares available for grant, beginning on January 1, 2015 through January 1, 2024. Eligible employees may purchase common stock at 85% of the lesser of the fair market value of common stock on the offering date or the purchase date with a six-month look-back feature. ESPP purchases are settled with common stock from the ESPP’s previously authorized and available pool of shares. During the year ended December 31, 2018, the Company issued 81,831 shares of common stock under the ESPP. As of December 31, 2018, an aggregate of 2,211,075 shares of common stock have been authorized for future issuance on the ESPP. Stock-Based Compensation Expense Total stock-based compensation recognized was as follows (in thousands): Year Ended December 31, 2018 2017 2016 Cost of sales $ 146 $ — $ — Research and development 45,572 38,212 29,412 Selling, general and administrative 34,389 29,802 18,897 Total stock-based compensation expense $ 80,107 $ 68,014 $ 48,309 Stock-based compensation of $1.1 million was capitalized into inventory for the year ended December 31, 2018. There was no stock-based compensation capitalized for the years ended December 31, 2017 and 2016. Capitalized stock-based compensation is recognized as cost of sales when the related product is sold. As of December 31, 2018, the total unrecognized compensation expense related to unvested equity awards, net of estimated forfeitures, was $131.0 million, which the Company expects to recognize over an estimated weighted-average period of 2.36 years. In determining the estimated fair value of the stock options and ESPP, the Company uses the Black-Scholes option-pricing model and assumptions discussed below. Each of these inputs is subjective and generally requires significant judgment to determine. Expected Term —The Company’s expected term represents the period that the Company’s stock-based awards are expected to be outstanding and is determined using the simplified method (based on the mid-point between the vesting date and the end of the contractual term). Expected Volatility —As the Company does not have sufficient historical stock price information from the Company to meet the expected life of the stock-based awards, our approach to estimating expected volatility is to phase in our own common stock trading history and supplement the remaining historical information with a blended volatility from the trading history for the common stock of a set of comparable publicly traded biopharmaceutical companies. Risk-Free Interest Rate —The risk-free interest rate is based on the U.S. Treasury zero coupon issues in effect at the time of grant for periods corresponding with the expected term of option. Expected Dividend —The Company has never paid dividends on its common stock and has no plans to pay dividends on its common stock. Therefore, the Company used an expected dividend yield of zero. The fair value of stock option awards granted was estimated at the date of grant using a Black-Scholes option-pricing model with the following weighted-average assumptions: Year Ended December 31, 2018 2017 2016 Expected term (years) 6.23 6.23 6.23 Expected volatility 62% 65% 65% Risk-free interest rate 2.7% 2.1% 1.5% Expected dividend rate 0.0% 0.0% 0.0%

Defined Contribution Plan

Defined Contribution Plan	12 Months Ended
	Dec. 31, 2018
Defined Contribution Pension And Other Postretirement Plans Disclosure [Abstract]
Defined Contribution Plan	12. Defined Contribution Plan The Company sponsors a retirement plan in which substantially all of its full-time employees in the United States and certain other foreign countries are eligible to participate. Eligible participants may contribute a percentage of their annual compensation to this plan, subject to statutory limitations. The Company recorded $2.9 million, $2.1 million, and $1.5 million as contribution expenses for the years ended December 31, 2018, 2017, and 2016, respectively.

Income Taxes

Income Taxes	12 Months Ended
	Dec. 31, 2018
Income Tax Disclosure [Abstract]
Income Taxes	13. Income Taxes The components of the Company’s loss before income taxes were as follows (in thousands): Year Ended December 31, 2018 2017 2016 Domestic $ 205,440 $ 250,917 $ 192,287 Foreign (8,343 ) 67,421 53,552 Total loss before income taxes $ 197,097 $ 318,338 $ 245,839 The components of the Company’s income tax provision were as follows (in thousands): Year Ended December 31, 2018 2017 2016 Current provision for income taxes: Federal $ — $ — $ — State 14 5 — International 500 42 35 Total current tax provision 514 47 35 Deferred tax benefit: Federal — (16,243 ) — State — (3 ) — International — — — Total deferred tax benefit — (16,246 ) — Total (benefit from) provision for income taxes $ 514 $ (16,199 ) $ 35 The Company has incurred net operating losses since inception. The Company has not reflected any benefit of such net operating loss carryforwards in the accompanying financial statements. The Company has established a full valuation allowance against its deferred tax assets due to the uncertainty surrounding the realization of such assets. The effective tax rate of our provision for income taxes differs from the federal statutory rate as follows: Year Ended December 31, 2018 2017 2016 Federal statutory income tax rate 21.0 % 34.0 % 34.0 % State income taxes, net of federal benefit — — 1.3 Federal tax credits 9.5 9.0 13.7 Other (0.2 ) (0.9 ) (0.3 ) Nondeductible permanent items (0.8 ) — — Stock-based compensation (0.8 ) (0.6 ) (1.4 ) Uncertain tax positions (1.9 ) (1.8 ) 2.0 Change in valuation allowance (26.8 ) (32.5 ) (41.9 ) Foreign rate differential (0.3 ) (7.2 ) (7.4 ) Change in federal tax rate — 5 — Provision for income taxes (0.3 ) 5.1 0.0 The tax effect of temporary differences that give rise to significant portions of the deferred tax assets is presented below (in thousands): Year Ended December 31, 2018 2017 Deferred tax assets: Loss carryforwards $ 183,331 $ 154,949 Tax credits 137,019 119,542 Stock options 29,925 21,336 Accruals and reserves 7,418 5,939 Fixed assets and intangibles 2,820 1,194 Other 1,189 1,286 Gross deferred tax assets 361,702 304,246 Valuation allowance (361,702 ) (304,246 ) Total deferred tax assets — — Deferred tax liabilities: In-process research and development (31,166 ) (31,166 ) Net deferred tax assets (liabilities) $ (31,166 ) $ (31,166 ) As of December 31, 2018 and 2017, the Company had $558.3 million and $422.3 million of federal net operating loss carryforwards available to reduce future taxable income that will begin to expire in 2030. As of December 31, 2018 and 2017, the Company had $476.8 million and $457.7 million of state net operating loss carryforwards available to reduce future taxable income that will begin to expire in 2030. As of December 31, 2018 and 2017, the Company had federal research tax credit carryforwards of $7.5 million and $4.5 million available to reduce future tax liabilities that will begin to expire in 2030. As of December 31, 2018 and 2017, the Company had state research credit carryforwards of $17.3 million and $12.4 million available to reduce future tax liabilities that will be carried forward indefinitely. As of December 31, 2018 and 2017, the Company had federal Orphan Drug Credits of $143.5 million and $124.6 million available to reduce future tax liabilities that will begin to expire in 2031. The Company’s ability to use net operating loss and tax credit carryforwards to reduce future taxable income and liabilities may be subject to annual limitations pursuant to Internal Revenue Code Sections 382 and 383 as a result of ownership changes in the past and future. As a result of ownership changes in 2012 and 2011, $3.6 million of federal net operating loss carryforwards, $3.6 million of state net operating loss carryforwards, and $0.2 million of federal tax credits are permanently limited. Deferred tax assets for net operating losses and tax credits have been reduced and a corresponding adjustment to the valuation allowance has been recorded. On November 7, 2017, the Company acquired Dimension (see Note 3 “Dimension Acquisition”). The Company recorded a $47.4 million deferred tax liability relating to the tax impact of future GAAP amortization or potential impairments associated with the identified intangible assets acquired, which are indefinitely lived assets and are not currently deductible for tax purposes. Due to the reduction of the US corporate tax rate to 21% in the period subsequent to the acquisition, the Company recorded a net decrease to the deferred tax liability of $16.2 million with a corresponding benefit from income taxes of $16.2 million for the year ended December 31, 2017. During the year ended December 31, 2018, the Company did not amortize or impair such acquired IPR&D. Therefore, there is no change to the deferred tax liability balance generated from Dimension acquisition. The valuation allowance increased by $57.5 million and $91.9 million during the year ended December 31, 2018 and 2017, respectively. On December 22, 2017, the U.S. government enacted comprehensive tax legislation commonly referred to as the Tax Cuts and Jobs Act (the “Tax Act”). The post-enactment items that have new impact to the 2018 tax accounting includes, but are not limited to, (1) global intangible low-taxed income (GILTI); (2) base erosion anti-abuse tax (BEAT); (3) foreign derived intangible income (FDII); (4) limitation on deductible interest expense, (5) certain non-deductible expenses, and (6) changing rules related to uses and limitations of net operating loss carryforwards created in tax years beginning after December 31, 2017. On December 22, 2017, Staff Accounting Bulletin No. 118 (SAB 118) was issued to address the application of GAAP in situations when a registrant does not have the necessary information available, prepared, or analyzed (including computations) in reasonable detail to complete the accounting for certain income tax effects of the Tax Act. In accordance with SAB 118, the Company recorded a provisional amount related to the remeasurement of certain deferred tax assets and liabilities based on the rates at which they are expected to reverse in the future. It was a net decrease related to deferred tax assets and deferred tax liabilities of $70.5 million, with a corresponding net adjustment to benefit from income taxes of $16.1 million and offsetting change in valuation allowance of $86.6 million for the year ended December 31, 2017. As of December 22, 2018, the Company has completed its accounting for the remeasurement of certain deferred tax assets and liabilities based on the rates at which they are expected to reverse in the future. There have been no net benefit changes to the provisional estimates disclosed in the period of enactment under SAB 118. The Company recorded unrecognized tax benefits for uncertainties in income taxes. A reconciliation of the Company’s unrecognized tax benefits follows (in thousands): December 31, 2018 2017 2016 Balance at beginning of year $ 28,377 $ 13,505 $ 24,010 Additions based on tax positions related to current year 4,750 9,338 6,777 Additions for tax positions of prior years 600 5,534 877 Reductions for tax positions of prior years — — (18,159 ) Balance at end of year $ 33,727 $ 28,377 $ 13,505 The entire amount of the unrecognized tax benefits would not impact the Company’s effective tax rate if recognized. The Company has elected to include interest and penalties as a component of tax expense. During the years ended December 31, 2018 and 2017, the Company did not recognize accrued interest and penalties related to unrecognized tax benefits. The Company does not anticipate that the amount of existing unrecognized tax benefits will significantly increase or decrease during the next year. It is our intention to reinvest the earnings of our non-U.S. subsidiaries in their operations. As of December 31, 2018, the Company had not made a provision for U.S. income taxes or foreign withholding taxes on approximately $3.7 million of the excess of the amount of net income for financial reporting over the tax basis of investments in foreign subsidiaries that are essentially permanent in duration. If these earnings were repatriated to the U.S., the deferred tax liability associated with these temporary differences would result in a nominal amount of withholding taxes. The Company files income tax returns in the U.S. federal, California, and other state tax jurisdictions. The federal and state income tax returns from inception to December 31, 2018 remain subject to examination.

Commitments and Contingencies

Commitments and Contingencies	12 Months Ended
	Dec. 31, 2018
Commitments And Contingencies Disclosure [Abstract]
Commitments and Contingencies	14. Commitments and Contingencies Facilities The Company leases office space and research, testing and manufacturing laboratory space in various facilities in Novato and Brisbane, California, in Cambridge and Woburn, Massachusetts, and in certain foreign countries, under operating agreements expiring at various dates through 2028. Certain of the leases provide for options by the Company to extend the lease for multiple five-year renewal periods and also provide for annual minimum increases in rent, usually based on a consumer price index or annual minimum increases. The Company recognizes rent expense on a straight-line basis over the noncancelable term of its operating leases. Rent expense was $6.4 million, $4.5 million, and $3.3 million during the years ended December 31, 2018, 2017, and 2016, respectively. Other Commitments The Company has various manufacturing, clinical, research, and other contracts with vendors in the conduct of the normal course of its business. Other than as noted below, contracts are terminable, with varying provisions regarding termination. If a contract with a specific vendor were to be terminated, the Company would only be obligated for the products or services that the Company had received at the time the termination became effective. As of December 31, 2018, the aggregate future minimum lease payments under the noncancelable operating lease arrangements and future payments under contractually binding manufacturing and service agreements are as follows (in thousands): Year Ending December 31, Leases Manufacturing and Services 2019 $ 5,965 $ 6,790 2020 4,588 62 2021 3,091 — 2022 2,831 — 2023 2,842 — Thereafter 8,451 — $ 27,768 $ 6,852 Contingencies While there are no material legal proceedings the Company is aware of, the Company may become party to various claims and complaints arising in the ordinary course of business. Management does not believe that any ultimate liability resulting from any of these claims will have a material adverse effect on its results of operations, financial position, or liquidity. However, management cannot give any assurance regarding the ultimate outcome of these claims, and their resolution could be material to operating results for any particular period, depending upon the level of income for the period. Guarantees and Indemnifications The Company indemnifies each of its directors and officers for certain events or occurrences, subject to certain limits, while the director is or was serving at the Company’s request in such capacity, as permitted under Delaware law and in accordance with its certificate of incorporation and bylaws. The term of the indemnification period lasts as long as a director may be subject to any proceeding arising out of acts or omissions of such director in such capacity. The maximum amount of potential future indemnification is unlimited; however, the Company currently holds director liability insurance. This insurance allows the transfer of risk associated with the Company’s exposure and may enable it to recover a portion of any future amounts paid. The Company believes that the fair value of these indemnification obligations is minimal. Accordingly, it has not recognized any liabilities relating to these obligations for any period presented.

Net Loss per Share

Net Loss per Share	12 Months Ended
	Dec. 31, 2018
Earnings Per Share [Abstract]
Net Loss per Share	15. Net Loss per Share The following table sets forth the computation of the basic and diluted net loss per share during the years ended December 31, 2018, 2017 and 2016 (in thousands, except share and per share data): Year Ended December 31, 2018 2017 2016 Numerator: Net loss $ (197,611 ) $ (302,139 ) $ (245,874 ) Denominator: Weighted-average shares used to compute net loss per share, basic and diluted 49,775,223 42,453,135 39,586,908 Net loss per share, basic and diluted $ (3.97 ) $ (7.12 ) $ (6.21 ) The following weighted-average outstanding common stock equivalents were excluded from the computation of diluted net loss per share for the periods presented because including them would have been antidilutive: Year Ended December 31, 2018 2017 2016 Options to purchase common stock, RSUs, and PSUs 7,301,431 5,862,784 4,699,111 Employee stock purchase plan 3,345 2,728 7,933 Common stock warrants 149,700 149,700 149,700 7,454,476 6,015,212 4,856,744

Accumulated Other Comprehensive

Accumulated Other Comprehensive Loss	12 Months Ended
	Dec. 31, 2018
Other Comprehensive Income Loss Net Of Tax Period Increase Decrease [Abstract]
Accumulated Other Comprehensive Loss	16. Accumulated Other Comprehensive Loss Total accumulated other comprehensive loss consisted of the following (in thousands) : Year Ended December 31, 2018 2017 Foreign currency translation adjustments $ (329 ) $ (5,298 ) Unrealized loss on securities available-for-sale (304 ) (382 ) Total accumulated other comprehensive loss $ (633 ) $ (5,680 )

Quarterly Financial Data (unaud

Quarterly Financial Data (unaudited)	12 Months Ended
	Dec. 31, 2018
Quarterly Financial Data [Abstract]
Quarterly Financial Data (unaudited)	17. Quarterly Financial Data (unaudited) The following table presents certain unaudited quarterly financial information. This information has been prepared on the same basis as the audited financial statements and includes all adjustments (consisting only of normal recurring adjustments) necessary to present fairly the unaudited quarterly results of operations set forth herein (in thousands, except per share data): 2018 March 31, June 30, September 30, December 31, Revenue $ 10,677 $ 12,794 $ 11,763 $ 16,261 Operating expenses $ 107,164 $ 107,694 $ 101,409 $ 106,601 Net income (loss) $ 30,253 $ (52,728 ) $ (87,310 ) $ (87,826 ) Net income (loss) per share, basic $ 0.63 $ (1.06 ) $ (1.74 ) $ (1.73 ) Net income (loss) per share, diluted $ 0.62 $ (1.06 ) $ (1.74 ) $ (1.73 ) 2017 March 31, June 30, September 30, December Revenue $ — $ — $ 198 $ 2,414 Operating expenses $ 69,954 $ 78,441 $ 83,911 $ 99,248 Net loss $ (68,290 ) $ (72,891 ) $ (79,227 ) $ (81,731 ) Net loss per share, basic and diluted $ (1.63 ) $ (1.72 ) $ (1.87 ) $ (1.89 )

Summary of Significant Accoun_2

Summary of Significant Accounting Policies (Policies)	12 Months Ended
	Dec. 31, 2018
Accounting Policies [Abstract]
Basis of Consolidation	Basis of Consolidation The consolidated financial statements include the accounts of Ultragenyx Pharmaceutical Inc. and our wholly-owned subsidiaries. All intercompany balances and transactions have been eliminated.
Use of Estimates	Use of Estimates The accompanying consolidated financial statements have been prepared in accordance with U.S. generally accepted accounting principles (“GAAP”). The preparation of the consolidated financial statements in conformity with GAAP requires management to make estimates and assumptions that affect the reported amounts of assets and liabilities, disclosure of contingent liabilities and the reported amounts of expenses in the consolidated financial statements and the accompanying notes. On an ongoing basis, management evaluates its estimates, including those related to clinical trial accruals, fair value of assets and liabilities, income taxes, and stock-based compensation. Management bases its estimates on historical experience and on various other market-specific and relevant assumptions that management believes to be reasonable under the circumstances. Actual results could differ from those estimates.
Cash, Cash Equivalents, and Restricted Cash	Cash, Cash Equivalents, and Restricted Cash The Company considers all highly liquid investments with original maturities of three months or less from the date of purchase to be cash equivalents. Cash equivalents consist primarily of amounts invested in money market accounts. Restricted cash primarily consists of money market accounts used as collateral for the Company’s obligations under its facility leases. In November 2016, the Financial Accounting Standards Board (FASB) issued Accounting Standards Update (ASU) 2016-18, Statement of Cash Flows (Topic 230): Restricted Cash December 31, 2018 2017 2016 Cash and cash equivalents $ 113,432 $ 100,488 $ 161,120 Restricted cash included in prepaid expenses and other current assets 271 461 1,411 Restricted cash included in other assets 1,822 2,092 2,076 Total cash, cash equivalents, and restricted cash shown in the statements of cash flows $ 115,525 $ 103,041 $ 164,607
Investments	Investments All investments have been classified as “available-for-sale” and are carried at estimated fair value as determined based upon quoted market prices or pricing models for similar securities. Management determines the appropriate classification of its investments at the time of purchase and reevaluates such designation as of each balance sheet date. Investments with a maturity of one year or less from the balance sheet date are reported as short-term investments and investments with a maturity of greater than one year from the balance sheet date are reported as long-term investments. Unrealized gains and losses are excluded from earnings and are reported as a component of comprehensive loss. Realized gains and losses and declines in fair value judged to be other than temporary, if any, on available-for-sale securities are included in other income (expense). The cost of securities sold is based on the specific-identification method. Interest on investments is included in interest income.
Concentration of Credit Risk and Other Risks and Uncertainties	Concentration of Credit Risk and Other Risks and Uncertainties Financial instruments that potentially subject the Company to a concentration of credit risk consist of cash, cash equivalents, and investments. The Company’s cash, cash equivalents, and investments are held by financial institutions that management believes are of high credit quality. The Company’s investment policy limits investments to fixed income securities denominated and payable in U.S. dollars such as U.S. government obligations, money market instruments and funds, corporate bonds, and asset-backed securities and places restrictions on maturities and concentrations by type and issuer. Such deposits may, at times, exceed federally insured limits. The Company has not experienced any losses on its deposits of cash and cash equivalents and its accounts are monitored by management to mitigate risk. The Company is exposed to credit risk in the event of default by the financial institutions holding its cash and cash equivalents, corporate bond issuers, and other financial instruments, to the extent recorded in the balance sheets . The Company has not experienced any credit losses to date from credit risk concentration. Concentration of credit risk with respect to is primarily limited to collaboration partners, drug wholesalers, and retail pharmacy distributors. Credit is extended to our customers based on an evaluation of a customer’s financial condition, and collateral is not The Company is dependent on third-party manufacturers to supply products for research and development activities in its programs. In particular, the Company relies and expects to continue to rely on a small number of manufacturers to supply it with its requirements for the active pharmaceutical ingredients and formulated drugs related to these programs. These programs could be adversely affected by a significant interruption in the supply of active pharmaceutical ingredients and formulated drugs.
Inventory	Inventory The Company values inventory at the lower of cost and net realizable value and determines the cost of inventory using the average-cost method. The Company expenses costs associated with the manufacture of product candidates prior to regulatory approval. Inventories consist of currently approved products. The Company periodically reviews its inventories for excess amounts or obsolescence and writes down obsolete or otherwise unmarketable inventory to its estimated net realizable value.
Property and Equipment	Property and Equipment Property and equipment are stated at cost, less accumulated depreciation and amortization. Depreciation and amortization is computed using the straight-line method over the estimated useful lives of the respective assets. Depreciation and amortization begins at the time the asset is placed in service. Maintenance and repairs are charged to operations as incurred. Upon sale or retirement of assets, the cost and related accumulated depreciation are removed from the balance sheet and the resulting gain or loss, if any, is reflected in operations. The useful lives of property and equipment are as follows: Research and development equipment 5 years Furniture and office equipment 5 years Computer equipment 3 years Software 3-5 years Leasehold improvements Shorter of lease term or estimated useful life
Intangible Assets	Intangible Assets The Company recognizes an acquired intangible apart from goodwill whenever the intangible arises from contractual or other legal rights, or whenever it can be separated or divided from the acquired entity and sold, transferred, licensed, rented or exchanged, either individually or in combination with a related contract, asset or liability. The Company’s intangible assets consist of acquired in-process research and development (IPR&D) and an acquired contract asset. IPR&D assets represent capitalized incomplete research projects that the Company acquired through business combinations. The Company tests its definite and indefinite-lived intangible assets for impairment annually during the fourth quarter and more frequently if events or changes in circumstances indicate that it is more likely than not that the asset is impaired. If it is determined that the asset becomes impaired, the carrying value is written down to its fair value with the related impairment charge recognized in consolidated statements of operations in the period in which the impairment occurs. The Company has not recorded any impairments of intangible assets.
Goodwill	Goodwill Goodwill represents the excess of purchase price over fair value of net assets acquired in a business combination and is not amortized. Goodwill is subject to impairment testing at least annually during the fourth quarter or when a triggering event occurs that could indicate a potential impairment. If it is determined that the goodwill becomes impaired, the carrying value is written down to its fair value with the related impairment charge recognized in consolidated statements of operations in the period in which the impairment occurs. The Company has not recorded any impairments of goodwill.
Impairment of Long-Lived Assets	Impairment of Long-Lived Assets The Company evaluates its long-lived assets, including property and equipment, for impairment whenever events or changes in circumstances indicate that the carrying value of these assets may not be recoverable. Recoverability of these assets is measured by comparison of the carrying amount of each asset to the future undiscounted cash flows expected to result from the use of the asset and its eventual disposition. If the asset is considered to be impaired, the amount of any impairment is measured as the difference between the carrying value and the fair value of the impaired asset. The Company has not recorded impairment of any long-lived assets.
Accruals of Research and Development Costs	Accruals of Research and Development Costs The Company records accruals for estimated costs of research, preclinical and clinical studies and manufacturing development. These costs are a significant component of the Company’s research and development expenses. A substantial portion of the Company’s ongoing research and development activities are conducted by third-party service providers, including contract research organizations. The Company accrues the costs incurred under its agreements with these third parties based on actual work completed in accordance with agreements established with these third parties. The Company determines the actual costs through discussions with internal personnel and external service providers as to the progress or stage of completion of the services and the agreed-upon fee to be paid for such services.
Revenue Recognition	Revenue Recognition Effective January 1, 2017, the Company adopted ASU 2014-09, Revenue from Contracts with Customers (ASC 606) Collaboration and license revenue The Company has certain license and collaboration agreements that are within the scope of Accounting Standards Codification (ASC) 808, Collaborative Agreements provides guidance on the presentation and disclosure of collaborative arrangements. Generally, the classification of the transactions under the collaborative arrangements is determined based on the nature of contractual terms of the arrangement, along with the nature of the operations of the participants. The Company records its share of collaboration revenue, net of transfer pricing related to net sales in the period in which such sales occur, if the Company is considered as an agent in the arrangement. The Company is considered an agent when the collaboration partner controls the product before transfer to the customers and has the ability to direct the use of and obtain substantially all of the remaining benefits from the product. Funding received related to research and development services and commercialization costs are generally classified as a reduction of research and development expenses and selling, general and administrative expenses, respectively, in the consolidated statement of operations, because the provision of such services for collaborative partners are not considered to be part of the Company’s ongoing major or central operations. The also receives royalty revenues under certain of the Company’s license or collaboration agreements in exchange for license of intellectual property. If the Company does not have any future performance obligations for these license or collaboration agreements, royalty revenue is recorded as the underlying sales occur. In to record collaboration revenue, the Company utilizes certain information from its , including revenue from the sale of the product, associated reserves on revenue, and costs incurred for development and sales activities. For the periods covered in the financial statements presented, there have been no significant or material changes to prior period estimates of revenues and expenses. The terms of the Company’s collaboration agreements may contain multiple performance obligations, which may include licenses and research and development activities. The Company evaluates these agreements under ASC 606, Revenue from Contracts with Customers , to determine the distinct performance obligations. The Company analogizes to ASC 606 for the accounting for distinct performance obligations for which there is a customer relationship. Prior to recognizing revenue, the Company makes estimates of the transaction price, including variable consideration that is subject to a constraint. Amounts of variable consideration are included in the transaction price to the extent that it is probable that a significant reversal in the amount of cumulative revenue recognized will not occur and when the uncertainty associated with the variable consideration is subsequently resolved. Total consideration may include nonrefundable upfront license fees, payments for research and development activities, reimbursement of certain third-party costs, payments based upon the achievement of specified milestones, and royalty payments based on product sales derived from the collaboration. If there are multiple distinct performance obligations, the Company allocates the transaction price to each distinct performance obligation based on its relative standalone selling price. The standalone selling price is generally determined based on the prices charged to customers or using expected cost plus margin. The Company estimates the efforts needed to complete the performance obligation and recognizes revenue by measuring the progress towards complete satisfaction of the performance obligation using an input measure. Product sales The Company sells its approved products through a limited number of distributors. Under ASC 606, revenue from product sales is recognized at the point in time when the delivery is made and when title and risk of loss transfers to these distributors. The Company also recognizes revenue from sales of certain products on a “named patient” basis, which are allowed in certain countries prior to the commercial approval of the product. Prior to recognizing revenue, the Company makes estimates of the transaction price, including any variable consideration that is subject to a constraint. Amounts of variable consideration are included in the transaction price to the extent that it is probable that a significant reversal in the amount of cumulative revenue recognized will not occur and when the uncertainty associated with the variable consideration is subsequently resolved. Product sales are recorded net of estimated government-mandated rebates and chargebacks, estimated product returns, and other deductions. Provisions for returns and other adjustments are provided for in the period the related revenue is recorded, as estimated by management.
Leases	Leases The Company enters into lease agreements for its office and laboratory facilities. These leases are classified as operating leases. Rent expense is recognized on a straight-line basis over the term of the lease and, accordingly, the Company records the difference between cash rent payments and the recognition of rent expense as a deferred rent liability. Incentives granted under the Company’s facilities leases, including allowances to fund leasehold improvements, are deferred and are recognized as adjustments to rental expense on a straight-line basis over the term of the lease.
Comprehensive Loss	Comprehensive Loss Comprehensive loss is the change in stockholders’ equity from transactions and other events and circumstances other than those resulting from investments by stockholders and distributions to stockholders. The Company’s other comprehensive loss is comprised of unrealized gains and losses on investments in available-for-sale securities and foreign currency translation adjustments.
Research and Development	Research and Development Research and development costs are expensed as incurred and consist of salaries and benefits, stock-based compensation expense, lab supplies and facility costs, as well as fees paid to other nonemployees and entities that conduct certain research and development activities on the Company’s behalf. Amounts incurred in connection with license agreements are also included in research and development expense. Nonrefundable advance payments for goods or services to be received in the future for use in research and development activities are deferred. The deferred amounts are expensed as the related goods are delivered or the services are performed.
Stock-Based Compensation	Stock-Based Compensation Stock-based awards issued to employees, including stock options, restricted stock units (RSUs), and performance stock units (PSUs) are recorded at fair value as of the grant date and recognized as expense on a straight-line basis over the employee’s requisite service period (generally the vesting period). PSUs vest only if certain specified criteria are achieved and the employees’ continued service requirements are met; therefore, the expense recognition occurs when the likelihood of the PSUs being earned is deemed probable. Stock compensation expense on awards expected to vest are recognized net of estimated forfeitures.
Income Taxes	Income Taxes The Company uses the liability method of accounting for income taxes. Under this method, deferred tax assets and liabilities are determined based on the differences between the financial reporting and the tax bases of assets and liabilities and are measured using the enacted tax rates and laws that will be in effect when the differences are expected to reverse. The Company must then assess the likelihood that the resulting deferred tax assets will be realized. A valuation allowance is provided when it is more likely than not that some portion or all of a deferred tax asset will not be realized. Due to the Company’s lack of earnings history, the net deferred tax assets have been fully offset by a valuation allowance. In conjunction with Dimension acquisition, a deferred tax liability was recorded reflecting the tax impact of the difference between the book basis and tax basis of acquired IPR&D. Such deferred income tax liability is not used to offset deferred tax assets when analyzing the Company’s valuation allowance as the acquired IPR&D is considered to have an indefinite life until the Company completes or abandons development of the acquired IPR&D. The Company recognizes benefits of uncertain tax positions if it is more likely than not that such positions will be sustained upon examination based solely on their technical merits, as the largest amount of benefit that is more likely than not to be realized upon the ultimate settlement. The Company’s policy is to recognize interest and penalties related to the underpayment of income taxes as a component of income tax expense or benefit. To date, there have been no interest or penalties charged in relation to the unrecognized tax benefits.
Foreign Currency	Foreign Currency Assets and liabilities of non-U.S. subsidiaries that operate in a local currency environment, where the local currency is the functional currency, are translated to U.S. dollars at exchange rates in effect at the balance sheet date, with the resulting translation adjustments directly recorded to a separate component of accumulated other comprehensive loss. Income and expense accounts are translated at average exchange rates for the period. Transactions which are not in the functional currency of the entity are remeasured into the functional currency and gains or losses resulting from the remeasurement recorded in other income (expense).
Net Loss per Share	Net Loss per Share Basic net loss per share is calculated by dividing the net loss by the weighted-average number of shares of common stock outstanding during the period, without consideration for common stock equivalents. Diluted net loss per share is the same as basic net loss per share, since the effects of potentially dilutive securities are antidilutive. In periods when we have incurred a net loss, options and warrants to purchase common stock are considered common stock equivalents, but have been excluded from the calculation of diluted net loss per share, as their effect is antidilutive.
Business Combinations	Business Combinations The Company applies the provisions of ASC 805, “Business Combinations” allocates
Recent Accounting Pronouncements	Recent Accounting Pronouncements In February 2016, the FASB issued ASU No. 2016-02, Leases (Topic 842) As of January 1, 2019, the Company expects to record a right-to-use asset in the range of $15.0 million to $18.4 million, short-term lease liability in the range of $4.1 million to $5.0 million, and long-term lease liability in the range of $15.7 million to $19.2 million and no adjustment to the retained earnings. The Company is continuing to evaluate the effect that this guidance will have on its Consolidated Financial Statements and related disclosures.

Summary of Significant Accoun_3

Summary of Significant Accounting Policies (Tables)	12 Months Ended
	Dec. 31, 2018
Accounting Policies [Abstract]
Summary of Reconciliation of Cash, Cash Equivalents and Restricted Cash	The following table provides a reconciliation of cash, cash equivalents, and restricted cash reported within the consolidated balance sheets that sum to the total of the amounts shown in the consolidated statement of cash flows (in thousands): December 31, 2018 2017 2016 Cash and cash equivalents $ 113,432 $ 100,488 $ 161,120 Restricted cash included in prepaid expenses and other current assets 271 461 1,411 Restricted cash included in other assets 1,822 2,092 2,076 Total cash, cash equivalents, and restricted cash shown in the statements of cash flows $ 115,525 $ 103,041 $ 164,607
Summary of Useful Lives of Property and Equipment	The useful lives of property and equipment are as follows: Research and development equipment 5 years Furniture and office equipment 5 years Computer equipment 3 years Software 3-5 years Leasehold improvements Shorter of lease term or estimated useful life

Dimension Acquisition (Tables)

Dimension Acquisition (Tables)	12 Months Ended
	Dec. 31, 2018
Business Combinations [Abstract]
Summary of Fair Value of Consideration Transferred	The acquisition date fair value of the consideration transferred for Dimension was approximately $164.1 million, which consisted of the following (in thousands): Cash payments $ 152,292 Fair value of vested stock options assumed 8,979 REGENX termination fee 2,850 Fair value of total consideration $ 164,121
Summary of Fair Values of Assets Acquired and Liabilities Assumed	The following table summarizes the fair values of assets acquired and liabilities assumed as of the date of acquisition (in thousands): Cash and cash equivalents $ 12,338 Short-term investments 9,737 Other current assets 11,155 Property and equipment 6,580 In-process research and development 129,000 Bayer collaboration agreement 13,526 Accounts payable and accrued liabilities (10,265 ) Notes payable (4,944 ) Deferred tax liabilities (47,412 ) Net identifiable net assets acquired 119,715 Goodwill 44,406 Net assets acquired $ 164,121
Summary of Supplemental Unaudited Pro Forma	The following supplemental unaudited pro forma information presents the financial results as if the acquisition had occurred on January 1, 2016 (in thousands): For the year ended December 31, 2017 2016 Total revenues $ 18,528 $ 12,684 Net loss 341,737 306,596

Fair Value Measurements (Tables

Fair Value Measurements (Tables)	12 Months Ended
	Dec. 31, 2018
Fair Value Disclosures [Abstract]
Summary of Financial Assets and Liabilities Measured on Recurring Basis	The following table sets forth the fair value of the Company’s financial assets and liabilities remeasured on a recurring basis based on the three-tier fair value hierarchy (in thousands): December 31, 2018 Gross Unrealized Fair Value Hierarchy Amortized Cost Gains Losses Estimated Fair Value Money market funds Level 1 $ 72,999 $ — $ — $ 72,999 Time deposits Level 2 10,000 — — 10,000 Corporate bonds Level 2 180,167 — (241 ) 179,926 Commercial paper Level 2 50,198 — — 50,198 Asset-backed securities Level 2 22,597 — (10 ) 22,587 U.S. Government Treasury and agency securities Level 2 99,087 2 (55 ) 99,034 Total $ 435,048 $ 2 $ (306 ) $ 434,744 December 31, 2017 Gross Unrealized Fair Value Hierarchy Amortized Cost Gains Losses Estimated Fair Value Money market funds Level 1 $ 79,670 $ — $ — $ 79,670 Corporate bonds Level 2 39,330 — (90 ) 39,240 U.S. Government Treasury and agency securities Level 2 105,031 — (292 ) 104,739 Total $ 224,031 $ — $ (382 ) $ 223,649

Balance Sheet Components (Table

Balance Sheet Components (Tables)	12 Months Ended
	Dec. 31, 2018
Investments Debt And Equity Securities [Abstract]
Summary of Inventory	Inventory consists of the following (in thousands): December 31, 2018 2017 Work-in-process $ 5,384 $ 737 Finished goods 1,681 20 Total inventory $ 7,065 $ 757
Summary of Property and Equipment	Property and equipment, net consists of the following (in thousands): December 31, 2018 2017 Leasehold improvements $ 15,705 $ 15,085 Research and development equipment 9,856 7,696 Furniture and office equipment 3,379 2,873 Computer equipment and software 7,342 6,745 Construction-in-progress 1,970 429 Property and equipment, gross 38,252 32,828 Less accumulated depreciation (18,206 ) (10,991 ) Property and equipment, net $ 20,046 $ 21,837
Accrued Liabilities	Accrued liabilities consists of the following (in thousands): December 31, 2018 2017 Research, clinical study, and manufacturing expenses $ 16,912 $ 17,141 Payroll and related expenses 36,443 26,527 Repayment liability under collaboration agreement — 3,681 Contract liability — 5,986 Other 9,095 8,793 Total accrued liabilities $ 62,450 $ 62,128

Revenue (Tables)

Revenue (Tables)	12 Months Ended
	Dec. 31, 2018
Revenue From Contract With Customer [Abstract]
Summary of Disaggregation of Total Revenues	The following table disaggregates total revenues from external customers by collaboration and license revenue and product sales (in thousands): Year Ended December 31, 2018 2017 2016 Collaboration and license revenue: KHK (Crysvita) $ 18,226 $ 9 $ — Bayer 23,467 2,127 — Total collaboration and license revenue 41,693 2,136 — Product sales: Crysvita 644 — — Mepsevii 7,903 476 133 UX007 1,255 — — Total product sales 9,802 476 133 Total revenues $ 51,495 $ 2,612 $ 133 The following table disaggregates total revenues based on geographic location (in thousands): Year Ended December 31, 2018 2017 2016 United States $ 45,339 $ 2,289 $ — Europe 5,293 323 133 All other 863 — — Total revenues $ 51,495 $ 2,612 $ 133
Schedule of Sales-Related Accruals and Allowances	The following table presents the activity and ending balances for sales-related accruals and allowances (in thousands): Product sales reserves December 31, 2016 $ — Provisions 41 December 31, 2017 41 Provisions 2,466 Payments and adjustments (1,267 ) December 31, 2018 $ 1,240
Summary of Changes in Contract Assets (Liabilities)	The following table presents changes in the contract assets (liabilities) for the years ended December 31, 2018 and 2017 (in thousands): December 31, 2018 2017 Balance of contract assets (liabilities) at beginning of year $ (5,986 ) $ — Contract liability assumed at acquisition — (2,526 ) Additions 24,055 4,658 Deductions (15,090 ) (8,118 ) Balance of contract assets (liabilities) at end of year $ 2,979 $ (5,986 )

License and Research Agreemen_2

License and Research Agreements (Tables)	12 Months Ended
	Dec. 31, 2018
Research Grant Agreement [Abstract]
Share of Collaboration and Royalty Revenue Related to Crysvita	The Company’s Year Ended December 31, 2018 2017 2016 Company's share of collaboration revenue in profit share territory $ 15,334 $ — $ — Royalty revenue in European territory 2,892 9 — Total $ 18,226 $ 9 $ —
Schedule of Cost Sharing Payments	Under the collaboration agreement, KHK and the Company share certain development and commercialization costs. Year Ended December 31, 2018 2017 2016 Research and development $ 32,240 $ 31,165 $ 25,356 Selling, general and administrative 14,228 4,466 1,532 Total $ 46,468 $ 35,631 $ 26,888

Stock-Based Awards (Tables)

Stock-Based Awards (Tables)	12 Months Ended
	Dec. 31, 2018
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Summary of Activity Under Stock Option Plans Including 2011 Plan and 2014 Plan	Stock Option Activity The following table summarizes activity under the Company’s stock option plans, including the 2011 Plan, the 2014 Plan, the assumed equity awards from the Dimension plans and related information: Options Outstanding Number of Options Weighted- Average Exercise Weighted-Average Remaining Contractual Term Aggregate Intrinsic Value (In Outstanding — December 31, 2015 3,826,963 $ 56.36 8.58 $ 217,386 Options granted 1,435,995 67.00 Options exercised (425,922 ) 21.21 Options cancelled (407,564 ) 70.87 Outstanding — December 31, 2016 4,429,472 $ 61.85 8.22 $ 79,135 Options granted 1,328,860 71.99 Options assumed 639,897 27.97 Options exercised (478,470 ) 16.25 Options cancelled (520,349 ) 78.70 Outstanding — December 31, 2017 5,399,410 $ 62.75 7.40 $ 37,687 Options granted 1,479,451 55.54 Options exercised (713,263 ) 36.21 Options cancelled (812,474 ) 74.80 Outstanding — December 31, 2018 5,353,124 $ 62.46 7.22 $ 23,243 Vested and exercisable — December 31, 2018 2,870,804 $ 62.10 6.09 $ 22,555 Vested and expected to vest — December 31, 2018 5,134,594 $ 62.53 7.16 $ 23,191
Summary of Stock-Based Compensation Expense	Total stock-based compensation recognized was as follows (in thousands): Year Ended December 31, 2018 2017 2016 Cost of sales $ 146 $ — $ — Research and development 45,572 38,212 29,412 Selling, general and administrative 34,389 29,802 18,897 Total stock-based compensation expense $ 80,107 $ 68,014 $ 48,309
Fair Value of Stock Option Awards Granted Estimated Using Black-Scholes Option-Pricing Model	The fair value of stock option awards granted was estimated at the date of grant using a Black-Scholes option-pricing model with the following weighted-average assumptions: Year Ended December 31, 2018 2017 2016 Expected term (years) 6.23 6.23 6.23 Expected volatility 62% 65% 65% Risk-free interest rate 2.7% 2.1% 1.5% Expected dividend rate 0.0% 0.0% 0.0%
Restricted Stock Units
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Summary of Activity Under Stock Units from 2014 Plan	The following table summarizes activity under the Company’s Restricted Stock Units (RSUs) from the 2014 Plan and related information: RSUs Outstanding Number of Shares Weighted- Average Grant Date Fair Value Unvested — December 31, 2015 197,151 $ 87.24 RSUs granted 477,816 66.83 RSUs released (52,273 ) 82.59 RSUs cancelled (48,950 ) 78.04 Unvested — December 31, 2016 573,744 $ 71.45 RSUs granted 516,161 71.58 RSUs released (156,021 ) 71.93 RSUs cancelled (112,324 ) 76.78 Unvested — December 31, 2017 821,560 $ 70.71 RSUs granted 555,905 56.01 RSUs released (235,913 ) 71.01 RSUs cancelled (187,475 ) 65.37 Unvested — December 31, 2018 954,077 $ 63.12
Performance Stock Units
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Summary of Activity Under Stock Units from 2014 Plan	The following table summarizes activity under the Company’s PSUs from the 2014 Plan and related information: PSUs Outstanding Number of Shares Weighted- Average Grant Date Fair Value Unvested — December 31, 2016 — $ — PSUs granted 508,850 48.03 Unvested — December 31, 2017 508,850 $ 48.03 PSUs granted 71,725 59.67 PSUs cancelled (97,375 ) 48.58 Unvested — December 31, 2018 483,200 $ 49.65

Income Taxes (Tables)

Income Taxes (Tables)	12 Months Ended
	Dec. 31, 2018
Income Tax Disclosure [Abstract]
Components of Company's Loss Before Income Taxes	The components of the Company’s loss before income taxes were as follows (in thousands): Year Ended December 31, 2018 2017 2016 Domestic $ 205,440 $ 250,917 $ 192,287 Foreign (8,343 ) 67,421 53,552 Total loss before income taxes $ 197,097 $ 318,338 $ 245,839
Components of Company's Income Tax Provision	The components of the Company’s income tax provision were as follows (in thousands): Year Ended December 31, 2018 2017 2016 Current provision for income taxes: Federal $ — $ — $ — State 14 5 — International 500 42 35 Total current tax provision 514 47 35 Deferred tax benefit: Federal — (16,243 ) — State — (3 ) — International — — — Total deferred tax benefit — (16,246 ) — Total (benefit from) provision for income taxes $ 514 $ (16,199 ) $ 35
Effective Tax Rate of Provision for Income Taxes from Federal Statutory Rate	The effective tax rate of our provision for income taxes differs from the federal statutory rate as follows: Year Ended December 31, 2018 2017 2016 Federal statutory income tax rate 21.0 % 34.0 % 34.0 % State income taxes, net of federal benefit — — 1.3 Federal tax credits 9.5 9.0 13.7 Other (0.2 ) (0.9 ) (0.3 ) Nondeductible permanent items (0.8 ) — — Stock-based compensation (0.8 ) (0.6 ) (1.4 ) Uncertain tax positions (1.9 ) (1.8 ) 2.0 Change in valuation allowance (26.8 ) (32.5 ) (41.9 ) Foreign rate differential (0.3 ) (7.2 ) (7.4 ) Change in federal tax rate — 5 — Provision for income taxes (0.3 ) 5.1 0.0
Schedule of Tax Effect of Temporary Differences to Significant Portions of Deferred Tax Assets	The tax effect of temporary differences that give rise to significant portions of the deferred tax assets is presented below (in thousands): Year Ended December 31, 2018 2017 Deferred tax assets: Loss carryforwards $ 183,331 $ 154,949 Tax credits 137,019 119,542 Stock options 29,925 21,336 Accruals and reserves 7,418 5,939 Fixed assets and intangibles 2,820 1,194 Other 1,189 1,286 Gross deferred tax assets 361,702 304,246 Valuation allowance (361,702 ) (304,246 ) Total deferred tax assets — — Deferred tax liabilities: In-process research and development (31,166 ) (31,166 ) Net deferred tax assets (liabilities) $ (31,166 ) $ (31,166 )
Unrecognized Tax Benefits	A reconciliation of the Company’s unrecognized tax benefits follows (in thousands): December 31, 2018 2017 2016 Balance at beginning of year $ 28,377 $ 13,505 $ 24,010 Additions based on tax positions related to current year 4,750 9,338 6,777 Additions for tax positions of prior years 600 5,534 877 Reductions for tax positions of prior years — — (18,159 ) Balance at end of year $ 33,727 $ 28,377 $ 13,505

Commitments and Contingencies (

Commitments and Contingencies (Tables)	12 Months Ended
	Dec. 31, 2018
Commitments And Contingencies Disclosure [Abstract]
Summary of Future Minimum Lease Payments under Non-Cancellable Operating Leases Arrangements and Future Payments under Contractually Binding Manufacturing and Service Agreements	As of December 31, 2018, the aggregate future minimum lease payments under the noncancelable operating lease arrangements and future payments under contractually binding manufacturing and service agreements are as follows (in thousands): Year Ending December 31, Leases Manufacturing and Services 2019 $ 5,965 $ 6,790 2020 4,588 62 2021 3,091 — 2022 2,831 — 2023 2,842 — Thereafter 8,451 — $ 27,768 $ 6,852

Net Loss per Share (Tables)

Net Loss per Share (Tables)	12 Months Ended
	Dec. 31, 2018
Earnings Per Share [Abstract]
Computation of Basic and Diluted Net Loss per Share	The following table sets forth the computation of the basic and diluted net loss per share during the years ended December 31, 2018, 2017 and 2016 (in thousands, except share and per share data): Year Ended December 31, 2018 2017 2016 Numerator: Net loss $ (197,611 ) $ (302,139 ) $ (245,874 ) Denominator: Weighted-average shares used to compute net loss per share, basic and diluted 49,775,223 42,453,135 39,586,908 Net loss per share, basic and diluted $ (3.97 ) $ (7.12 ) $ (6.21 )
Outstanding Shares of Common Stock Equivalents Excluded from Computation of Diluted Net Loss per Share	The following weighted-average outstanding common stock equivalents were excluded from the computation of diluted net loss per share for the periods presented because including them would have been antidilutive: Year Ended December 31, 2018 2017 2016 Options to purchase common stock, RSUs, and PSUs 7,301,431 5,862,784 4,699,111 Employee stock purchase plan 3,345 2,728 7,933 Common stock warrants 149,700 149,700 149,700 7,454,476 6,015,212 4,856,744

Accumulated Other Comprehensi_2

Accumulated Other Comprehensive Loss (Tables)	12 Months Ended
	Dec. 31, 2018
Other Comprehensive Income Loss Net Of Tax Period Increase Decrease [Abstract]
Schedule of Total Accumulated Other Comprehensive Loss	Total accumulated other comprehensive loss consisted of the following (in thousands) : Year Ended December 31, 2018 2017 Foreign currency translation adjustments $ (329 ) $ (5,298 ) Unrealized loss on securities available-for-sale (304 ) (382 ) Total accumulated other comprehensive loss $ (633 ) $ (5,680 )

Quarterly Financial Data (una_2

Quarterly Financial Data (unaudited) (Tables)	12 Months Ended
	Dec. 31, 2018
Quarterly Financial Data [Abstract]
Summary of Unaudited Quarterly Financial Information	The following table presents certain unaudited quarterly financial information. This information has been prepared on the same basis as the audited financial statements and includes all adjustments (consisting only of normal recurring adjustments) necessary to present fairly the unaudited quarterly results of operations set forth herein (in thousands, except per share data): 2018 March 31, June 30, September 30, December 31, Revenue $ 10,677 $ 12,794 $ 11,763 $ 16,261 Operating expenses $ 107,164 $ 107,694 $ 101,409 $ 106,601 Net income (loss) $ 30,253 $ (52,728 ) $ (87,310 ) $ (87,826 ) Net income (loss) per share, basic $ 0.63 $ (1.06 ) $ (1.74 ) $ (1.73 ) Net income (loss) per share, diluted $ 0.62 $ (1.06 ) $ (1.74 ) $ (1.73 ) 2017 March 31, June 30, September 30, December Revenue $ — $ — $ 198 $ 2,414 Operating expenses $ 69,954 $ 78,441 $ 83,911 $ 99,248 Net loss $ (68,290 ) $ (72,891 ) $ (79,227 ) $ (81,731 ) Net loss per share, basic and diluted $ (1.63 ) $ (1.72 ) $ (1.87 ) $ (1.89 )

Organization and Basis of Pre_2

Organization and Basis of Presentation - Additional Information (Details)	12 Months Ended
	Dec. 31, 2018Segment
United States of America
Organization And Nature Of Business [Line Items]
Number of reportable segments	1

Summary of Significant Accoun_4

Summary of Significant Accounting Policies - Summary of Reconciliation of Cash, Cash Equivalents and Restricted Cash (Details) - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Accounting Policies [Abstract]
Cash and cash equivalents	$ 113,432	$ 100,488	$ 161,120
Restricted cash included in prepaid expenses and other current assets	$ 271	$ 461	$ 1,411
Restricted Cash and Cash Equivalents, Current, Asset, Statement of Financial Position [Extensible List]	us-gaap:PrepaidExpensesAndOtherCurrentAssetsMember	us-gaap:PrepaidExpensesAndOtherCurrentAssetsMember	us-gaap:PrepaidExpensesAndOtherCurrentAssetsMember
Restricted cash included in other assets	$ 1,822	$ 2,092	$ 2,076
Restricted Cash and Cash Equivalents, Noncurrent, Asset, Statement of Financial Position [Extensible List]	us-gaap:OtherNoncurrentAssetsMember	us-gaap:OtherNoncurrentAssetsMember	us-gaap:OtherNoncurrentAssetsMember
Total cash, cash equivalents, and restricted cash shown in the statements of cash flows	$ 115,525	$ 103,041	$ 164,607	$ 95,854

Summary of Significant Accoun_5

Summary of Significant Accounting Policies - Additional Information (Details) - USD ($)	12 Months Ended
	Dec. 31, 2018	Jan. 01, 2019
Summary Of Significant Accounting Policies [Line Items]
Allowance for doubtful accounts	$ 0
Unrecognized tax benefits related to interest or penalties	$ 0
Subsequent Event | Accounting Standards Update 2016-02
Summary Of Significant Accounting Policies [Line Items]
Lease, term		12 months
Adjustment to retained earnings		$ 0
Subsequent Event | Accounting Standards Update 2016-02 | Minimum
Summary Of Significant Accounting Policies [Line Items]
Right-to-use-asset		15,000,000
Short-term lease liability		4,100,000
Long-term lease liability		15,700,000
Subsequent Event | Accounting Standards Update 2016-02 | Maximum
Summary Of Significant Accounting Policies [Line Items]
Right-to-use-asset		18,400,000
Short-term lease liability		5,000,000
Long-term lease liability		$ 19,200,000

Summary of Significant Accoun_6

Summary of Significant Accounting Policies - Summary of Useful Lives of Property and Equipment (Details)	12 Months Ended
	Dec. 31, 2018
Research and Development Equipment
Property Plant And Equipment [Line Items]
Property plant and equipment useful life	5 years
Furniture and Office Equipment
Property Plant And Equipment [Line Items]
Property plant and equipment useful life	5 years
Computer Equipment
Property Plant And Equipment [Line Items]
Property plant and equipment useful life	3 years
Software | Minimum
Property Plant And Equipment [Line Items]
Property plant and equipment useful life	3 years
Software | Maximum
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 lease term or estimated useful life

Dimension Acquisition - Additio

Dimension Acquisition - Additional Information (Details) - USD ($)	Nov. 07, 2017	Dec. 31, 2017	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
Business Acquisition [Line Items]
Decrease in deferred tax liability												$ 16,200,000
Federal statutory income tax rate											21.00%	34.00%	34.00%
Total revenues			$ 16,261,000	$ 11,763,000	$ 12,794,000	$ 10,677,000	$ 2,414,000	$ 198,000			$ 51,495,000	$ 2,612,000	$ 133,000
Net loss			(87,826,000)	$ (87,310,000)	$ (52,728,000)	$ 30,253,000	$ (81,731,000)	$ (79,227,000)	$ (72,891,000)	$ (68,290,000)	$ (197,611,000)	(302,139,000)	(245,874,000)
Dimension
Business Acquisition [Line Items]
Business acquisition date	Nov. 7, 2017
Business acquisition, purchase price per share	$ 6
Business acquisition, cash	$ 152,292,000
REGENX termination fee paid	2,850,000
Business acquisition, assumed equity awards value	15,400,000
Business acquisition, acceleration of certain awards recognized as expense in post-combination financial statements	2,200,000
Business acquisition, being recognized as expense over employee's remaining service period	4,200,000
Business acquisition, consideration transferred	164,121,000
Non-current deferred tax liability	47,412,000
Decrease in deferred tax liability												$ 31,200,000
Federal statutory income tax rate											21.00%	34.00%
Notes payable	4,944,000
Transaction costs	6,000,000
Notes payable			$ 0								$ 0
Total revenues		$ 2,100,000
Net loss		$ 7,500,000
Transaction costs related to acquisition												$ 9,600,000
Amortization of definite-lived intangible assets												$ 1,800,000	$ 11,100,000
Stock Options | Dimension
Business Acquisition [Line Items]
Business acquisition, assumed equity awards value	$ 8,979,000

Dimension Acquisition - Summary

Dimension Acquisition - Summary of Fair Value of Consideration Transferred (Details) - Dimension $ in Thousands	Nov. 07, 2017USD ($)
Business Acquisition [Line Items]
Cash payments	$ 152,292
Fair value of vested stock options assumed	15,400
REGENX termination fee	2,850
Fair value of total consideration	164,121
Stock Options
Business Acquisition [Line Items]
Fair value of vested stock options assumed	$ 8,979

Dimension Acquisition - Summa_2

Dimension Acquisition - Summary of Fair Values of Assets Acquired and Liabilities Assumed (Details) - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017	Nov. 07, 2017
Business Acquisition [Line Items]
Goodwill	$ 44,406	$ 44,406
Dimension
Business Acquisition [Line Items]
Cash and cash equivalents			$ 12,338
Short-term investments			9,737
Other current assets			11,155
Property and equipment			6,580
In-process research and development			129,000
Bayer collaboration agreement			13,526
Accounts payable and accrued liabilities			(10,265)
Notes payable			(4,944)
Deferred tax liabilities			(47,412)
Net identifiable net assets acquired			119,715
Goodwill			44,406
Net assets acquired			$ 164,121

Dimension Acquisition - Summa_3

Dimension Acquisition - Summary of Supplemental Unaudited Pro Forma (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016
Business Combinations [Abstract]
Total revenues	$ 18,528	$ 12,684
Net loss	$ 341,737	$ 306,596

Fair Value Measurements - Summa

Fair Value Measurements - Summary of Financial Assets and Liabilities Measured on Recurring Basis (Details) - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Amortized Cost	$ 435,048	$ 224,031
Gross Unrealized Gains	2
Gross Unrealized Losses	(306)	(382)
Estimated Fair Value	434,744	223,649
Money Market Funds | Level 1
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Amortized Cost	72,999	79,670
Estimated Fair Value	72,999	79,670
Asset-backed Securities | Level 2
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Amortized Cost	22,597
Gross Unrealized Losses	(10)
Estimated Fair Value	22,587
Time Deposits | Level 2
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Amortized Cost	10,000
Estimated Fair Value	10,000
Corporate Bonds | Level 2
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Amortized Cost	180,167	39,330
Gross Unrealized Losses	(241)	(90)
Estimated Fair Value	179,926	39,240
Commercial Paper | Level 2
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Amortized Cost	50,198
Estimated Fair Value	50,198
U.S. Government Treasury and Agency Securities | Level 2
Fair Value Assets And Liabilities Measured On Recurring And Nonrecurring Basis [Line Items]
Amortized Cost	99,087	105,031
Gross Unrealized Gains	2
Gross Unrealized Losses	(55)	(292)
Estimated Fair Value	$ 99,034	$ 104,739

Fair Value Measurements - Addit

Fair Value Measurements - Additional Information (Details)	12 Months Ended
	Dec. 31, 2018USD ($)
Schedule Of Available For Sale Securities [Line Items]
Significant realized gains or losses on available-for-sale securities	$ 0
Maximum
Schedule Of Available For Sale Securities [Line Items]
Available-for-sale securities remaining contractual maturities	1 year

Balance Sheet Components - Summ

Balance Sheet Components - Summary of Inventory (Details) - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
Investments Debt And Equity Securities [Abstract]
Work-in-process	$ 5,384	$ 737
Finished goods	1,681	20
Total inventory	$ 7,065	$ 757

Balance Sheet Components - Su_2

Balance Sheet Components - Summary of Property and Equipment (Details) - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
Property Plant And Equipment [Line Items]
Property and equipment, gross	$ 38,252	$ 32,828
Less accumulated depreciation	(18,206)	(10,991)
Property and equipment, net	20,046	21,837
Leasehold Improvements
Property Plant And Equipment [Line Items]
Property and equipment, gross	15,705	15,085
Research and Development Equipment
Property Plant And Equipment [Line Items]
Property and equipment, gross	9,856	7,696
Furniture and Office Equipment
Property Plant And Equipment [Line Items]
Property and equipment, gross	3,379	2,873
Computer Equipment and Software
Property Plant And Equipment [Line Items]
Property and equipment, gross	7,342	6,745
Construction-in-progress
Property Plant And Equipment [Line Items]
Property and equipment, gross	$ 1,970	$ 429

Balance Sheet Components - Addi

Balance Sheet Components - Additional Information (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Property Plant And Equipment [Abstract]
Depreciation expense	$ 7.2	$ 4.8	$ 3.4

Balance Sheet Components - Accr

Balance Sheet Components - Accrued Liabilities (Details) - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
Payables And Accruals [Abstract]
Research, clinical study, and manufacturing expenses	$ 16,912	$ 17,141
Payroll and related expenses	36,443	26,527
Repayment liability under collaboration agreement		3,681
Contract liability		5,986
Other	9,095	8,793
Total accrued liabilities	$ 62,450	$ 62,128

Intangible Assets, Net - Additi

Intangible Assets, Net - Additional Information (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016	Nov. 07, 2017
Finite Lived Intangible Assets [Line Items]
Research and development expense related to amortization of assets	$ 293,998	$ 231,644	$ 183,204
Intangible asset impairment charges	0
Dimension
Finite Lived Intangible Assets [Line Items]
Business combination recognized intangible assets				$ 129,000
Research and development expense related to amortization of assets	12,300	$ 1,000
Estimated future amortization expense in 2019	200
Dimension | IPR&D Assets
Finite Lived Intangible Assets [Line Items]
Business combination recognized intangible assets				129,000
Dimension | Contract Asset
Finite Lived Intangible Assets [Line Items]
Business combination recognized intangible assets				$ 13,500
Remaining value of contract asset	$ 200

Revenue - Summary of Disaggrega

Revenue - Summary of Disaggregation of Total Revenues from External Customers (Details) - 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	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Total revenues
Total revenues	$ 16,261	$ 11,763	$ 12,794	$ 10,677	$ 2,414	$ 198	$ 51,495	$ 2,612	$ 133
Bayer HealthCare LLC
Total revenues
Total revenues							23,500	2,100
Collaboration and License
Total revenues
Total revenues							41,693	2,136
Collaboration and License | Kyowa Hakko Kirin Collaboration
Total revenues
Total revenues							18,226	9
Collaboration and License | Bayer HealthCare LLC
Total revenues
Total revenues							23,467	2,127
Product Sales
Total revenues
Total revenues							9,802	476	133
Product Sales | Crysvita
Total revenues
Total revenues							644
Product Sales | Mepsevii
Total revenues
Total revenues							7,903	$ 476	$ 133
Product Sales | UX007
Total revenues
Total revenues							$ 1,255

Revenue - Summary of Disaggre_2

Revenue - Summary of Disaggregation of Total Revenues (Details) - 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	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Disaggregation Of Revenue [Line Items]
Total revenues	$ 16,261	$ 11,763	$ 12,794	$ 10,677	$ 2,414	$ 198	$ 51,495	$ 2,612	$ 133
United States
Disaggregation Of Revenue [Line Items]
Total revenues							45,339	2,289
Europe
Disaggregation Of Revenue [Line Items]
Total revenues							5,293	$ 323	$ 133
All other
Disaggregation Of Revenue [Line Items]
Total revenues							$ 863

Revenue - Schedule of Sales-Rel

Revenue - Schedule of Sales-Related Accruals and Allowances (Details) - Product Sales - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017
Disaggregation Of Revenue [Line Items]
Sales reserves, Beginning balance	$ 41
Provisions	2,466	$ 41
Payments and adjustments	(1,267)
Sales reserves, Ending balance	$ 1,240	$ 41

Revenue - Summary of Changes in

Revenue - Summary of Changes in Contract Assets (Liabilities) (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017
Disaggregation Of Revenue [Abstract]
Contract liabilities	$ (5,986)
Contract liability assumed at acquisition		$ (2,526)
Additions	24,055	4,658
Deductions	(15,090)	(8,118)
Contract assets	$ 2,979
Contract liabilities		$ (5,986)

Revenue - Additional Informatio

Revenue - Additional Information (Details)	Dec. 31, 2018	Dec. 31, 2017
Disaggregation Of Revenue [Abstract]
Percentage of gross accounts receivable balance	88.00%	97.00%

License and Research Agreemen_3

License and Research Agreements - Additional Information (Details)	Nov. 07, 2017USD ($)	Oct. 31, 2018USD ($)	Jun. 30, 2018USD ($)	Oct. 31, 2015USD ($)	Dec. 31, 2017USD ($)	Dec. 31, 2018USD ($)	Sep. 30, 2018USD ($)	Jun. 30, 2018USD ($)	Mar. 31, 2018USD ($)	Dec. 31, 2017USD ($)	Sep. 30, 2017USD ($)	Dec. 31, 2018USD ($)DiseaseIndication	Dec. 31, 2017USD ($)	Dec. 31, 2016USD ($)
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Collaboration and license revenue						$ 16,261,000	$ 11,763,000	$ 12,794,000	$ 10,677,000	$ 2,414,000	$ 198,000	$ 51,495,000	$ 2,612,000	$ 133,000
Research and development												293,998,000	231,644,000	183,204,000
Contract asset						2,979,000						2,979,000
Dimension
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Collaboration and license revenue					$ 2,100,000
Business acquisition date	Nov. 7, 2017
Business combination recognized intangible assets	$ 129,000,000
Research and development												$ 12,300,000	1,000,000
Amortization completion year												2,019
Dimension | Contract Asset
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Business combination recognized intangible assets	13,500,000
Bayer HealthCare LLC
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Collaboration and license revenue												$ 23,500,000	2,100,000
Contract liability	$ 2,500,000				5,400,000					5,400,000			5,400,000
Contract asset						3,000,000						3,000,000
Product Sales
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Collaboration and license revenue												9,802,000	476,000	133,000
Kyowa Hakko Kirin Collaboration
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Reduction in research and development expenses												32,240,000	31,165,000	$ 25,356,000
Kyowa Hakko Kirin Collaboration | License Agreement
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Collaboration and license revenue												15,300,000
Kyowa Hakko Kirin Collaboration | License Agreement | Prepaid and Other Current Assets
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
License agreement other receivables						11,100,000						11,100,000
Kyowa Hakko Kirin Collaboration | License Agreement | Product Sales
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Collaboration and license revenue												600,000
Kyowa Hakko Kirin Collaboration | License Agreement | Profit Share Revenue
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
License agreement accounts receivable					9,000	11,200,000				9,000		$ 11,200,000	9,000
Kyowa Hakko Kirin Collaboration | License Agreement | Commercial and Development Activity Reimbursements
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
License agreement other receivables					10,300,000					10,300,000			10,300,000
Kyowa Hakko Kirin Collaboration | Profit Share Territory | License Agreement
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Remaining profit or loss share percentage on commercializing products												50.00%
Tiered double-digit revenue share percentage entitled to receive												20.00%
Kyowa Hakko Kirin Collaboration | European Territory | License Agreement | Maximum
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Percentage of royalty on net sales entitled to receive												10.00%
Saint Louis University License Agreement
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Milestone payments paid												$ 100,000
Baylor Research Institute License Agreement | Development Milestones
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Future contingent milestone payments						5,300,000						5,300,000
Baylor Research Institute License Agreement | Sales Milestones
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Future contingent milestone payments						7,500,000						$ 7,500,000
Option and License Agreement | REGENXBIO, Inc.
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Option and license agreement description												The Company also has an option and license agreement with REGENX under which the Company has an exclusive, sublicensable, worldwide license to make, have made, use, import, sell, and offer for sale licensed products with respect to three disease indications, subject to certain exclusions and has an option for another disease indication. In October 2018, the Company exercised its remaining option with REGENX for the additional disease indication and paid a $1.0 million fee for the exercise of the option.
Number of disease indications for exclusive license | DiseaseIndication												3
Fee paid for exercise of option		$ 1,000,000
Annual maintenance fee for each option exercised												$ 100,000
Option and License Agreement | Maximum | REGENXBIO, Inc.
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Future contingent milestone payments						9,000,000						9,000,000
Research, Develop and Commercialize AAV Gene Therapy Products | Bayer HealthCare LLC
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Milestone payments received												15,000,000
Research, Develop and Commercialize AAV Gene Therapy Products | Maximum | Bayer HealthCare LLC
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Future contingent milestone payments						232,000,000						232,000,000
Research Collaboration and License Agreement Development Milestones | Maximum | University of Pennsylvania School of Medicine (Penn)
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Future contingent milestone payments						5,000,000						5,000,000
Research Collaboration and License Agreement Commercial Milestones | Maximum | University of Pennsylvania School of Medicine (Penn)
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Future contingent milestone payments						25,000,000						25,000,000
Takeda License and Collaboration and Purchase Agreements
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Contract liability					600,000	0				600,000		0	600,000
Research and development amount paid			$ 10,600,000
Collaborative agreement reduction in transaction price			14,300,000
Remaining transaction price			$ 3,700,000
Reduction in research and development expenses												1,200,000	2,500,000
Repayment liability					$ 3,700,000	$ 0				$ 3,700,000		$ 0	$ 3,700,000
Arcturus Research Collaboration and License Agreement
Collaborative Arrangements And Noncollaborative Arrangement Transactions [Line Items]
Research and development				$ 10,000,000

License and Research Agreemen_4

License and Research Agreements - Share of Collaboration and Royalty Revenue Related to Crysvita (Details) - 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	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Disaggregation Of Revenue [Line Items]
Collaboration and royalty revenue	$ 16,261	$ 11,763	$ 12,794	$ 10,677	$ 2,414	$ 198	$ 51,495	$ 2,612	$ 133
Collaboration and Royalty | Kyowa Hakko Kirin Collaboration
Disaggregation Of Revenue [Line Items]
Collaboration and royalty revenue							18,226	9
Collaboration and Royalty | Kyowa Hakko Kirin Collaboration | Profit Share Territory
Disaggregation Of Revenue [Line Items]
Collaboration and royalty revenue							15,334
Collaboration and Royalty | Kyowa Hakko Kirin Collaboration | Royalty Revenue in European Territory
Disaggregation Of Revenue [Line Items]
Collaboration and royalty revenue							$ 2,892	$ 9

License and Research Agreemen_5

License and Research Agreements - Schedule of Cost Sharing Payments (Details) - Kyowa Hakko Kirin Collaboration - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Cost Sharing Payments [Line Items]
Research and development	$ 32,240	$ 31,165	$ 25,356
Selling, general and administrative	14,228	4,466	1,532
Total	$ 46,468	$ 35,631	$ 26,888

Gain from Sale of Priority Re_2

Gain from Sale of Priority Review Vouchers - Additional Information (Details) - USD ($) $ in Thousands	1 Months Ended		12 Months Ended
	Jun. 30, 2018	Jan. 31, 2018	Dec. 31, 2018
Finite Lived Intangible Assets [Line Items]
Sale of PRV			$ 170,322
Gain from sale of priority review vouchers			$ 170,322
Mepsevii
Finite Lived Intangible Assets [Line Items]
Sale of PRV		$ 130,000
Crysvita
Finite Lived Intangible Assets [Line Items]
Sale of PRV	$ 80,600

Equity - Additional Information

Equity - Additional Information (Details) - USD ($)	Feb. 19, 2019	Jan. 31, 2018	Jul. 31, 2017	Jul. 31, 2016	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Stockholders Equity [Line Items]
Net proceeds from sale of common stock					$ 270,969,000
Common Stock Warrants Expiring on 2020
Stockholders Equity [Line Items]
Common stock warrants outstanding					149,700	149,700
Common stock warrants, exercise price					$ 3.01	$ 3.01
Common stock warrants, expiration period					2,020	2,020
Common Stock Warrants Expiring on 2021
Stockholders Equity [Line Items]
Common stock warrants outstanding					149,700	149,700
Common stock warrants, exercise price					$ 3.01	$ 3.01
Common stock warrants, expiration period					2,021	2,021
ATM Sales Agreement
Stockholders Equity [Line Items]
Option to sell common stock for cash				$ 150,000,000
Common stock shares sold						912,351	1,159,415
Net proceeds from sale of common stock						$ 67,600,000	$ 79,500,000
ATM Sales Agreement | Subsequent Event
Stockholders Equity [Line Items]
Common stock shares sold	379,707
Net proceeds from sale of common stock	$ 19,300,000
Additional ATM Sales Agreement
Stockholders Equity [Line Items]
Common stock shares sold					640,257	1,338,866
Net proceeds from sale of common stock					$ 38,100,000	$ 64,300,000
Additional ATM Sales Agreement | Maximum
Stockholders Equity [Line Items]
Option to sell common stock for cash			$ 150,000,000
Underwritten Public Offering
Stockholders Equity [Line Items]
Common stock shares sold		5,043,860
Net proceeds from sale of common stock		$ 271,000,000
Shares purchased by underwriters		657,895
Public offering price		$ 57

Stock-Based Awards - Additional

Stock-Based Awards - Additional Information (Details) - USD ($)	Nov. 07, 2017	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016	Feb. 05, 2014	Jan. 31, 2014
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Total intrinsic value of options exercised		$ 22,900,000	$ 20,400,000	$ 22,200,000
Cash received from exercise of options		$ 25,800,000	$ 7,800,000	$ 9,000,000
Weighted-average estimated fair value of stock option		$ 33.32	$ 44.20	$ 40.49
Total estimated fair value of options vested		$ 51,700,000	$ 49,100,000	$ 43,800,000
Total unrecognized compensation cost		$ 131,000,000
Weighted-average period to recognize cost		2 years 4 months 9 days
Stock-based compensation capitalized		$ 1,058,000	$ 0	$ 0
Dimension
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Options assumed to purchase shares of common stock from acquisition	639,897
Restricted Stock Units
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Shares vested during the period		235,913	156,021	52,273
Total fair value of shares vested		$ 16,800,000
Aggregate intrinsic value		$ 14,900,000
Maximum | Restricted Stock Units
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Stock based awards vesting period		4 years
Minimum | Restricted Stock Units
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Stock based awards vesting period		1 year
2014 Incentive Plan
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Share of common stock authorized for future issuance					2,250,000
Automatic increases in shares available for grant effective date		Jan. 1, 2015
Shares available for grant, ending date		Jan. 1, 2024
2014 Incentive Plan | Employee Stock Option
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Minimum percentage of voting rights of all classes of stock		10.00%
Percentage of statutory stock awards		110.00%
2014 Incentive Plan | Maximum | Employee Stock Option
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Award expiration period		10 years
2011 Equity Incentive Plan
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Share of common stock authorized for future issuance					655,038
2011 Equity Incentive Plan | Restricted Stock Units
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Option vesting rights, percentage		25.00%
Stock based awards vesting period		4 years
2011 Equity Incentive Plan | First Anniversary | Employee Stock Option
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Option vesting rights, percentage		25.00%
2011 Equity Incentive Plan | Shares Vesting Monthly After First Anniversary | Employee Stock Option
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Option vesting rights, percentage		2.08%
2011 Equity Incentive Plan and 2014 Incentive Plan
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Share of common stock authorized for future issuance		8,845,990
2014 Employee Stock Purchase Plan
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Share of common stock authorized for future issuance		2,211,075
Automatic increases in shares available for grant effective date		Jan. 1, 2015
Shares available for grant, ending date		Jan. 1, 2024
Percentage of statutory stock awards		85.00%
Share of common stock available for future issuance						600,000
Common stock shares issued		81,831

Stock-Based Awards - Summary of

Stock-Based Awards - Summary of Activity Under Stock Option Plans Including 2011 Plan and 2014 Plan (Details) - USD ($) $ / shares in Units, $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Disclosure Of Compensation Related Costs Sharebased Payments [Abstract]
Number of Options, Outstanding, Beginning Balance	5,399,410	4,429,472	3,826,963
Number of Options, Options granted	1,479,451	1,328,860	1,435,995
Number of Options, Options assumed		639,897
Number of Options, Options exercised	(713,263)	(478,470)	(425,922)
Number of Options, Options cancelled	(812,474)	(520,349)	(407,564)
Number of Options, Outstanding, Ending Balance	5,353,124	5,399,410	4,429,472	3,826,963
Number of Options, Vested and exercisable — December 31, 2018	2,870,804
Number of Options, Vested and expected to vest — December 31, 2018	5,134,594
Weighted Average Exercise Price, Outstanding, Beginning Balance	$ 62.75	$ 61.85	$ 56.36
Weighted Average Exercise Price, Options granted	55.54	71.99	67
Weighted Average Exercise Price, Options assumed		27.97
Weighted Average Exercise Price, Options exercised	36.21	16.25	21.21
Weighted Average Exercise Price, Options cancelled	74.80	78.70	70.87
Weighted Average Exercise Price, Outstanding, Ending Balance	62.46	$ 62.75	$ 61.85	$ 56.36
Weighted Average Exercise Price, Vested and exercisable — December 31, 2018	62.10
Weighted Average Exercise Price, Vested and expected to vest — December 31, 2018	$ 62.53
Weighted Average Remaining Contractual Term (Years), Outstanding	7 years 2 months 19 days	7 years 4 months 24 days	8 years 2 months 19 days	8 years 6 months 29 days
Weighted Average Remaining Contractual Term (Years), Vested and exercisable — December 31, 2018	6 years 1 month 2 days
Weighted Average Remaining Contractual Term (Years), Vested and expected to vest — December 31, 2018	7 years 1 month 28 days
Aggregate Intrinsic Value, Outstanding	$ 23,243	$ 37,687	$ 79,135	$ 217,386
Aggregate Intrinsic Value, Vested and exercisable — December 31, 2018	22,555
Aggregate Intrinsic Value, Vested and expected to vest — December 31, 2018	$ 23,191

Stock-Based Awards - Summary _2

Stock-Based Awards - Summary of Activity Under Restricted Stock Units (RSUs) from 2014 Plan (Details) - Restricted Stock Units - $ / shares	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Outstanding, Number of Shares, Unvested, Beginning Balance	821,560	573,744	197,151
Number of Shares, granted	555,905	516,161	477,816
Number of Shares, released	(235,913)	(156,021)	(52,273)
Number of Shares, cancelled	(187,475)	(112,324)	(48,950)
Outstanding, Number of Shares, Unvested, Ending Balance	954,077	821,560	573,744
Outstanding, Weighted-Average Grant Date Fair Value, Unvested, Beginning Balance	$ 70.71	$ 71.45	$ 87.24
Weighted-Average Grant Date Fair Value, granted	56.01	71.58	66.83
Weighted-Average Grant Date Fair Value, released	71.01	71.93	82.59
Weighted-Average Grant Date Fair Value, cancelled	65.37	76.78	78.04
Outstanding, Weighted-Average Grant Date Fair Value, Unvested, Ending Balance	$ 63.12	$ 70.71	$ 71.45

Stock-Based Awards - Summary _3

Stock-Based Awards - Summary of Activity Under PSUs from 2014 Plan (Details) - Performance Stock Units - $ / shares	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Outstanding, Number of Shares, Unvested, Beginning Balance	508,850
Number of Shares, granted	71,725	508,850
Number of Shares, cancelled	(97,375)
Outstanding, Number of Shares, Unvested, Ending Balance	483,200	508,850
Outstanding, Weighted-Average Grant Date Fair Value, Unvested, Beginning Balance	$ 48.03
Weighted-Average Grant Date Fair Value, granted	59.67	$ 48.03
Weighted-Average Grant Date Fair Value, cancelled	48.58
Outstanding, Weighted-Average Grant Date Fair Value, Unvested, Ending Balance	$ 49.65	$ 48.03

Stock-Based Awards - Summary _4

Stock-Based Awards - Summary of Stock-Based Compensation Recognized (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Employee Service Share Based Compensation Allocation Of Recognized Period Costs [Line Items]
Stock-based compensation expense	$ 80,107	$ 68,014	$ 48,309
Cost of sales
Employee Service Share Based Compensation Allocation Of Recognized Period Costs [Line Items]
Stock-based compensation expense	146
Research and development
Employee Service Share Based Compensation Allocation Of Recognized Period Costs [Line Items]
Stock-based compensation expense	45,572	38,212	29,412
Selling, general and administrative
Employee Service Share Based Compensation Allocation Of Recognized Period Costs [Line Items]
Stock-based compensation expense	$ 34,389	$ 29,802	$ 18,897

Stock-Based Awards - Fair Value

Stock-Based Awards - Fair Value of Stock Option Awards Granted Estimated Using Black-Scholes Option-Pricing Model (Details) - Employee Stock Option	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Share Based Compensation Arrangement By Share Based Payment Award [Line Items]
Expected term (years)	6 years 2 months 23 days	6 years 2 months 23 days	6 years 2 months 23 days
Expected volatility	62.00%	65.00%	65.00%
Risk-free interest rate	2.70%	2.10%	1.50%
Expected dividend rate	0.00%	0.00%	0.00%

Defined Contribution Plan - Add

Defined Contribution Plan - Additional Information (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Defined Contribution Pension And Other Postretirement Plans Disclosure [Abstract]
Contribution expenses	$ 2.9	$ 2.1	$ 1.5

Income Taxes - Components of Co

Income Taxes - Components of Company's Loss Before Income Taxes (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Income Tax Disclosure [Abstract]
Domestic	$ 205,440	$ 250,917	$ 192,287
Foreign	(8,343)	67,421	53,552
Total loss before income taxes	$ 197,097	$ 318,338	$ 245,839

Income Taxes - Components of _2

Income Taxes - Components of Company's Income Tax Provision (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Current provision for income taxes:
State	$ 14	$ 5
International	500	42	$ 35
Total current tax provision	514	47	35
Deferred tax benefit:
Federal		(16,243)
State		(3)
Total deferred tax benefit		(16,246)
Total (benefit from) provision for income taxes	$ 514	$ (16,199)	$ 35

Income Taxes - Effective Tax Ra

Income Taxes - Effective Tax Rate of Provision for Income Taxes from Federal Statutory Rate (Details)	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Effective Income Tax Rate Continuing Operations Tax Rate Reconciliation [Abstract]
Federal statutory income tax rate	21.00%	34.00%	34.00%
State income taxes, net of federal benefit			1.30%
Federal tax credits	9.50%	9.00%	13.70%
Other	(0.20%)	(0.90%)	(0.30%)
Nondeductible permanent items	(0.80%)
Stock-based compensation	(0.80%)	(0.60%)	(1.40%)
Uncertain tax positions	(1.90%)	(1.80%)	2.00%
Change in valuation allowance	(26.80%)	(32.50%)	(41.90%)
Foreign rate differential	(0.30%)	(7.20%)	(7.40%)
Change in federal tax rate		5.00%
Provision for income taxes	(0.30%)	5.10%	0.00%

Income Taxes - Schedule of Tax

Income Taxes - Schedule of Tax Effect of Temporary Differences to Significant Portions of Deferred Tax Assets (Details) - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2012	Dec. 31, 2011
Deferred tax assets:
Loss carryforwards	$ 183,331	$ 154,949	$ 200	$ 200
Tax credits	137,019	119,542
Stock options	29,925	21,336
Accruals and reserves	7,418	5,939
Fixed assets and intangibles	2,820	1,194
Other	1,189	1,286
Gross deferred tax assets	361,702	304,246
Valuation allowance	(361,702)	(304,246)
Deferred tax liabilities:
Net deferred tax assets (liabilities)	(31,166)	(31,166)
In-process Research and Development
Deferred tax liabilities:
In-process research and development	$ (31,166)	$ (31,166)

Income Taxes - Additional Infor

Income Taxes - Additional Information (Details) - USD ($)	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016	Nov. 07, 2017	Dec. 31, 2012	Dec. 31, 2011
Tax Credit Carryforward [Line Items]
Deferred tax assets net operating loss carryforwards	$ 183,331,000	$ 154,949,000			$ 200,000	$ 200,000
Deferred tax liability decrease, net		16,200,000
Benefit from (provision for) income taxes	(514,000)	16,199,000	$ (35,000)
Valuation allowance increased	57,500,000	91,900,000
Net decrease to deferred tax assets and deferred tax liabilities		70,500,000
Net adjustment to benefit from income taxes		16,100,000
Change in valuation allowance		86,600,000
Unrecognized tax benefits, income tax penalties and interest accrued	0	0
Undistributed earnings of foreign subsidiaries	3,700,000
Dimension
Tax Credit Carryforward [Line Items]
Deferred tax liability				$ 47,412,000
Deferred tax liability decrease, net		31,200,000
Federal
Tax Credit Carryforward [Line Items]
Deferred tax assets operating loss carryforwards subject to expiration	$ 558,300,000	422,300,000
Operating loss carryforwards expiration year	2,030
Tax credit carryforwards	$ 7,500,000	4,500,000
Tax credit carryforwards expiration year	2,030
Deferred tax assets net operating loss carryforwards					3,600,000	3,600,000
Federal | Orphan Drug Credits [Member]
Tax Credit Carryforward [Line Items]
Deferred tax assets operating loss carryforwards subject to expiration	$ 143,500,000	124,600,000
Operating loss carryforwards expiration year	2,031
State
Tax Credit Carryforward [Line Items]
Deferred tax assets operating loss carryforwards subject to expiration	$ 476,800,000	457,700,000
Operating loss carryforwards expiration year	2,030
Tax credit carryforwards	$ 17,300,000	$ 12,400,000
Deferred tax assets net operating loss carryforwards					$ 3,600,000	$ 3,600,000

Income Taxes - Unrecognized Tax

Income Taxes - Unrecognized Tax Benefits (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Income Tax Disclosure [Abstract]
Balance at beginning of year	$ 28,377	$ 13,505	$ 24,010
Additions based on tax positions related to current year	4,750	9,338	6,777
Additions for tax positions of prior years	600	5,534	877
Reductions for tax positions of prior years			(18,159)
Balance at end of year	$ 33,727	$ 28,377	$ 13,505

Commitments and Contingencies -

Commitments and Contingencies - Additional Information (Details) - USD ($) $ in Millions	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Disclosure Commitments And Contingencies Additional Information Details [Line Items]
Rent expense	$ 6.4	$ 4.5	$ 3.3
Novato Office Facility
Disclosure Commitments And Contingencies Additional Information Details [Line Items]
Operating lease expiration year	2,028
Lease renewal term	5 years

Commitments and Contingencies_2

Commitments and Contingencies - Summary of Future Minimum Lease Payments under Non-Cancellable Operating Leases Arrangements and Future Payments under Contractually Binding Manufacturing and Service Agreements (Details) $ in Thousands	Dec. 31, 2018USD ($)
Commitments And Contingencies Disclosure [Abstract]
Leases, 2019	$ 5,965
Leases, 2020	4,588
Leases, 2021	3,091
Leases, 2022	2,831
Leases, 2023	2,842
Leases, Thereafter	8,451
Leases, Total	27,768
Manufacturing and Services, 2019	6,790
Manufacturing and Services, 2020	62
Manufacturing and Services, Total	$ 6,852

Net Loss per Share - Computatio

Net Loss per Share - Computation of Basic and Diluted Net Loss per Share (Details) - 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
Numerator:
Net loss	$ (87,826)	$ (87,310)	$ (52,728)	$ 30,253	$ (81,731)	$ (79,227)	$ (72,891)	$ (68,290)	$ (197,611)	$ (302,139)	$ (245,874)
Denominator:
Weighted-average shares used to compute net loss per share, basic and diluted									49,775,223	42,453,135	39,586,908
Net loss per share, basic and diluted					$ (1.89)	$ (1.87)	$ (1.72)	$ (1.63)	$ (3.97)	$ (7.12)	$ (6.21)

Net Loss per Share - Outstandin

Net Loss per Share - Outstanding Shares of Common Stock Equivalents Excluded from Computation of Diluted Net Loss per Share (Details) - shares	12 Months Ended
	Dec. 31, 2018	Dec. 31, 2017	Dec. 31, 2016
Antidilutive Securities Excluded From Computation Of Earnings Per Share [Line Items]
Common stock equivalents excluded from computation of diluted net loss per share	7,454,476	6,015,212	4,856,744
Options to Purchase Common Stock, RSUs, and PSUs
Antidilutive Securities Excluded From Computation Of Earnings Per Share [Line Items]
Common stock equivalents excluded from computation of diluted net loss per share	7,301,431	5,862,784	4,699,111
Common Stock Warrants
Antidilutive Securities Excluded From Computation Of Earnings Per Share [Line Items]
Common stock equivalents excluded from computation of diluted net loss per share	149,700	149,700	149,700
Employee Stock Purchase Plan
Antidilutive Securities Excluded From Computation Of Earnings Per Share [Line Items]
Common stock equivalents excluded from computation of diluted net loss per share	3,345	2,728	7,933

Accumulated Other Comprehensi_3

Accumulated Other Comprehensive Loss - Schedule of Total Accumulated Other Comprehensive Loss (Details) - USD ($) $ in Thousands	Dec. 31, 2018	Dec. 31, 2017
Accumulated Other Comprehensive Income Loss Net Of Tax [Abstract]
Foreign currency translation adjustments	$ (329)	$ (5,298)
Unrealized loss on securities available-for-sale	(304)	(382)
Total accumulated other comprehensive loss	$ (633)	$ (5,680)

Quarterly Financial Data (una_3

Quarterly Financial Data (unaudited) - Summary of Unaudited Quarterly Financial Information (Details) - 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
Selected Quarterly Financial Information [Abstract]
Collaboration and royalty revenue	$ 16,261	$ 11,763	$ 12,794	$ 10,677	$ 2,414	$ 198			$ 51,495	$ 2,612	$ 133
Operating expenses	106,601	101,409	107,694	107,164	99,248	83,911	$ 78,441	$ 69,954	422,868	331,554	248,140
Net income (loss)	$ (87,826)	$ (87,310)	$ (52,728)	$ 30,253	$ (81,731)	$ (79,227)	$ (72,891)	$ (68,290)	$ (197,611)	$ (302,139)	$ (245,874)
Net income (loss) per share, basic	$ (1.73)	$ (1.74)	$ (1.06)	$ 0.63
Net income (loss) per share, diluted	$ (1.73)	$ (1.74)	$ (1.06)	$ 0.62
Net loss per share, basic and diluted					$ (1.89)	$ (1.87)	$ (1.72)	$ (1.63)	$ (3.97)	$ (7.12)	$ (6.21)