PTC Therapeutics (PTCT) 10-Q 3 Nov 16 2016 Q3 Quarterly report Financial data

Document and Entity Information

Document and Entity Information - shares	9 Months Ended
	Sep. 30, 2016	Nov. 01, 2016
Document and Entity Information
Entity Registrant Name	PTC THERAPEUTICS, INC.
Entity Central Index Key	1,070,081
Document Type	10-Q
Document Period End Date	Sep. 30, 2016
Amendment Flag	false
Current Fiscal Year End Date	--12-31
Entity Current Reporting Status	Yes
Entity Filer Category	Large Accelerated Filer
Entity Common Stock, Shares Outstanding		34,318,169
Document Fiscal Year Focus	2,016
Document Fiscal Period Focus	Q3

Consolidated Balance Sheets (un

Consolidated Balance Sheets (unaudited) - USD ($) $ in Thousands	Sep. 30, 2016	Dec. 31, 2015
Current assets:
Cash and cash equivalents	$ 50,286	$ 58,022
Marketable securities	198,052	280,903
Prepaid expenses and other current assets	4,860	5,930
Trade receivables, net	27,409	11,094
Total current assets	280,607	355,949
Fixed assets, net	7,059	8,974
Deposits and other assets	511	358
Total assets	288,177	365,281
Current liabilities:
Accounts payable and accrued expenses	47,759	45,247
Deferred revenue	910	139
Other current liabilities	257	0
Total current liabilities	48,926	45,386
Long-term debt	96,559	91,848
Other long-term liabilities	2,515	2,046
Total liabilities	148,000	139,280
Stockholders’ equity:
Common stock, $0.001 par value. Authorized 125,000,000 shares; issued and outstanding 34,165,519 shares at September 30, 2016. Authorized 125,000,000 shares; issued and outstanding 33,916,559 shares at December 31, 2015	34	34
Additional paid-in capital	847,700	820,165
Accumulated other comprehensive income (loss)	756	(1,200)
Accumulated deficit	(708,313)	(592,998)
Total stockholders’ equity	140,177	226,001
Total liabilities and stockholders’ equity	$ 288,177	$ 365,281

Consolidated Balance Sheets (u3

Consolidated Balance Sheets (unaudited) (Parenthetical) - $ / shares	Sep. 30, 2016	Dec. 31, 2015
Statement of Financial Position [Abstract]
Common stock, par value (in dollars per share)	$ 0.001	$ 0.001
Common stock, authorized shares (in shares)	125,000,000	125,000,000
Common stock, issued shares (in shares)	34,165,519	33,916,559
Common stock, outstanding shares (in shares)	34,165,519	33,916,559

Consolidated Statements of Oper

Consolidated Statements of Operations (unaudited) - USD ($) $ in Thousands	3 Months Ended		9 Months Ended
	Sep. 30, 2016	Sep. 30, 2015	Sep. 30, 2016	Sep. 30, 2015
Revenues:
Net product revenue	$ 22,013	$ 9,772	$ 56,328	$ 21,002
Collaboration and grant revenue	973	4	1,186	3,030
Total revenues	22,986	9,776	57,514	24,032
Operating expenses:
Research and development	31,396	30,640	91,622	86,768
Selling, general and administrative	23,654	21,368	72,958	56,193
Total operating expenses	55,050	52,008	164,580	142,961
Loss from operations	(32,064)	(42,232)	(107,066)	(118,929)
Interest (expense) income, net	(2,133)	(852)	(6,149)	170
Other expense, net	(786)	(51)	(1,893)	(507)
Loss before income tax expense	(34,983)	(43,135)	(115,108)	(119,266)
Income tax expense	(184)	(88)	(206)	(233)
Net loss attributable to common stockholders	$ (35,167)	$ (43,223)	$ (115,314)	$ (119,499)
Weighted-average shares outstanding:
Basic and diluted (in shares)	34,088,741	33,908,853	34,002,952	33,528,833
Net loss per share-basic and diluted (in dollars per share)
Net loss per share—basic and diluted (in dollars per share)	$ (1.03)	$ (1.27)	$ (3.39)	$ (3.56)

Consolidated Statements of Comp

Consolidated Statements of Comprehensive Loss (unaudited) - USD ($) $ in Thousands	3 Months Ended		9 Months Ended
	Sep. 30, 2016	Sep. 30, 2015	Sep. 30, 2016	Sep. 30, 2015
Statement of Comprehensive Income [Abstract]
Net loss	$ (35,167)	$ (43,223)	$ (115,314)	$ (119,499)
Other comprehensive loss:
Unrealized (loss) gain on marketable securities, net of tax	(189)	(483)	429	(582)
Foreign currency translation gain (loss)	60	(149)	1,527	192
Comprehensive loss	$ (35,296)	$ (43,855)	$ (113,358)	$ (119,889)

Consolidated Statements of Cash

Consolidated Statements of Cash Flows (unaudited) - USD ($) $ in Thousands	9 Months Ended
	Sep. 30, 2016	Sep. 30, 2015
Cash flows from operating activities
Net loss	$ (115,314)	$ (119,499)
Adjustments to reconcile net loss to net cash used in operating activities:
Depreciation	2,477	2,079
Change in valuation of warrant liability	44	(152)
Non-cash interest expense	4,487	736
Amortization of premiums on investments	1,610	1,319
Amortization of debt issuance costs	224	37
Share-based compensation expense	26,610	26,130
Benefit for deferred income taxes	(222)	0
Unrealized foreign currency transaction losses, net	1,401	0
Changes in operating assets and liabilities:
Prepaid expenses and other current assets	1,095	(748)
Trade receivables, net	(16,035)	(3,582)
Deposits and other assets	(154)	183
Accounts payable and accrued expenses	2,080	2,871
Other long-term liabilities	682	(69)
Deferred revenue	768	(3,310)
Net cash used in operating activities	(90,247)	(94,005)
Cash flows from investing activities
Purchases of fixed assets	(540)	(1,764)
Purchases of marketable securities	(73,692)	(134,299)
Sale and redemption of marketable securities	155,582	167,082
Net cash provided by investing activities	81,350	31,019
Cash flows from financing activities
Proceeds from exercise of options	926	8,689
Debt issuance costs related to convertible notes	0	(4,650)
Proceeds from issuance of convertible notes	0	150,000
Net cash provided by financing activities	926	154,039
Effect of exchange rate changes on cash	235	(89)
Net (decrease) increase in cash and cash equivalents	(7,736)	90,964
Cash and cash equivalents, beginning of period	58,022	49,748
Cash and cash equivalents, end of period	50,286	140,712
Supplemental disclosure of cash information
Cash paid for interest	4,513	0
Cash paid for income taxes	633	0
Supplemental disclosures of non-cash information related to investing and financing activities
Change in unrealized gain (loss) on marketable securities, net of tax	$ 429	$ (582)

The Company

The Company	9 Months Ended
	Sep. 30, 2016
Organization, Consolidation and Presentation of Financial Statements [Abstract]
The Company	The Company PTC Therapeutics, Inc. (the “Company” or “PTC”) was incorporated as a Delaware corporation on March 31, 1998. PTC is a global biopharmaceutical company focused on the discovery, development and commercialization of orally administered, small molecule therapeutics targeting an area of RNA biology referred to as post transcriptional control. Post-transcriptional control processes are the regulatory events that occur in cells during and after a messenger RNA molecule is copied from DNA through the transcription process. PTC has discovered all of its compounds currently under development using its proprietary technologies. PTC plans to continue to develop these compounds both on its own and through selective collaboration arrangements with leading pharmaceutical and biotechnology companies. PTC’s internally discovered pipeline addresses multiple therapeutic areas, including rare disorders and oncology. PTC’s lead product candidate is ataluren, an investigational new drug in the United States, for the treatment of patients with genetic disorders that arise from a type of genetic mutation known as a nonsense mutation. The Company holds worldwide commercialization rights to ataluren for all indications in all territories. The brand name of ataluren is Translarna TM . The Company received conditional marketing authorization from the European Commission in August 2014 for Translarna for the treatment of nonsense mutation Duchenne muscular dystrophy, or nmDMD, in ambulatory patients aged five years and older in the 31 member states of the European Economic Area, or EEA. The marketing authorization is subject to annual review and renewal by the European Commission following reassessment by the European Medicines Agency, or EMA, of the risk-benefit balance of the authorization, or the annual EMA reassessment, as well as the Company’s satisfaction of any conditions and obligations that have been or may be placed upon the marketing authorization. The Company expects that the EMA's Committee for Medicinal Products for Human Use, or CHMP, will adopt an opinion as to whether to renew the Company's marketing authorization by the end of 2016. During 2016, the Company’s revenues have been, and are expected to be, primarily generated from sales of Translarna for the treatment of nmDMD in countries in the EEA where pricing and reimbursement approval is obtained at acceptable levels and in other territories where the Company is permitted to distribute Translarna under reimbursed early access programs, or EAPs. If the Company's marketing authorization in the EEA is not renewed, or the product label applicable to the marketing authorization is materially restricted, the Company would lose all, or a significant portion of, its ability to generate revenue from product sales, whether pursuant to a commercial or an EAP program and throughout all territories. The Company is subject to a number of risks similar to those of other early stage companies, including dependence on key individuals, the difficulties inherent in the development of commercially usable products, the potential need to obtain additional capital necessary to fund the development of its products, and competition from other companies. As of September 30, 2016 , the Company had an accumulated deficit of approximately $708.3 million . The Company has financed its operations to date primarily through the private offering in August 2015 of 3.00% convertible senior notes due 2022 (see Note 9), public offerings of common stock in February 2014 and October 2014, its initial public offering of common stock in June 2013, private placements of its convertible preferred stock, collaborations, bank debt, convertible debt financings, grant funding and clinical trial support from governmental and philanthropic organizations and patient advocacy groups in the disease area addressed by the Company’s product candidates.

Summary of significant accounti

Summary of significant accounting policies	9 Months Ended
	Sep. 30, 2016
Accounting Policies [Abstract]
Summary of significant accounting policies	Summary of significant accounting policies The Company’s complete listing of significant accounting policies are described in Note 2 of the notes to the Company’s audited financial statements as of December 31, 2015 included in the Company’s Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC) on February 29, 2016 (2015 Form 10-K). Basis of Presentation The accompanying financial information as of September 30, 2016 and for the three and nine months ended September 30, 2016 and 2015 has been prepared by the Company, without audit, pursuant to the rules and regulations of the SEC. Certain information and footnote disclosures normally included in financial statements prepared in accordance with generally accepted accounting principles in the United States (GAAP) have been condensed or omitted pursuant to such rules and regulations. These interim financial statements should be read in conjunction with the Company’s audited financial statements as of December 31, 2015 and notes thereto included in the 2015 Form 10-K. In the opinion of management, the unaudited financial information as of September 30, 2016 and for the three and nine months ended September 30, 2016 and 2015 reflects all adjustments, which are normal recurring adjustments, necessary to present a fair statement of financial position, results of operations and cash flows. The results of operations for the three and nine month periods ended September 30, 2016 are not necessarily indicative of the results to be expected for the year ended December 31, 2016 or for any other interim period or for any other future year. Use of estimates The preparation of financial statements in conformity with GAAP requires management to make estimates and assumptions that affect the amounts reported in the financial statements and accompanying notes. Significant estimates in these consolidated financial statements have been made in connection with the calculation of net product sales, certain accruals related to the Company’s research and development expenses, stock-based compensation, valuation procedures for the convertible notes, allowance for doubtful accounts and the provision for or benefit from income taxes. Actual results could differ from those estimates. Changes in estimates are reflected in reported results in the period in which they become known. Inventories and cost of product revenue In 2014, the Company was notified that the European Commission, or EC, granted marketing authorization for Translarna for the treatment of nmDMD in ambulatory patients aged five years and older. The conditional marketing authorization allows the Company to market Translarna for the treatment of nmDMD in the 31 member states of European Economic Area. The launch in these countries is on a country by country basis. This marketing authorization is subject to annual review and renewal by the EC following reassessment by the European Medicines Agency, or EMA, of the risk benefit balance of the authorization, which the Company refers to as the annual EMA reassessment. The authorization was further conditioned on the Company’s submission of the final report, including additional efficacy and safety data, from ACT DMD and the Company’s ability to implement measures, including pharmacovigilance plans that are detailed in the risk management plan for Translarna that was submitted to EMA. In January 2016, the Company submitted the final ACT DMD report to the EMA. The Company made this submission as a type II variation request that sought to have this initial condition to its marketing authorization removed and a full marketing authorization granted. In February 2016, the Company also submitted a marketing authorization renewal request with the EMA. The annual EMA reassessment process related to the Company's 2016 marketing authorization request is still ongoing and, as of the time of this filing, renewal has not been granted. The Company expects that the EMA's CHMP will adopt an opinion as to whether to renew the Company's marketing authorization for Translarna for the treatment of nmDMD by the end of 2016. Pursuant to applicable regulations, the Company expects that its current marketing authorization status (which was last renewed by the European Commission in the third quarter of 2015) will remain valid while the 2016 annual EMA reassessment is ongoing and until it is concluded with an opinion from the European Commission with respect to renewal of the marketing authorization. In the event that the Company's marketing authorization renewal request is granted, the Company plans to seek to renew the marketing authorization on an annual basis until any further obligations or conditions that may be placed by the EC on the marketing authorization have been fulfilled and the approval is converted from a conditional approval into a full approval. If the Company fails to satisfy such further obligations or conditions, or if it is determined that the balance of risks and benefits of using Translarna changes materially, the EC could, at the EMA’s recommendation, vary, suspend, withdraw or refuse to renew the marketing authorization for Translarna or require additional clinical trials. There continues to be substantial risk that regulators could suspend or not renew the Company’s marketing authorization in the future. As such, as of the date of this filing, the Company has not capitalized inventory given the near-term uncertainty with respect to the long-term utilization of Translarna finished product for commercial use. Had the Company capitalized as inventory all of the its Translarna product that is available for commercial sale on hand as of September 30, 2016 , the value of that inventory would have been approximately $1.3 million . In addition, had the Company expensed the cost of Translarna product sold as a cost of sales, the gross profit margin would have been greater than 90% , which the Company believes is consistent with the cost of producing small molecule therapeutics for orphan drug diseases in the pharmaceutical industry. The Company will continue to assess the appropriateness of inventory capitalization based on the outcome of applicable regulatory determinations, including the pending CHMP opinion regarding the potential annual renewal of our marketing authorization in the EEA, which is expected to be issued in 2016 and followed by ratification by the EC in early 2017. In the event the CHMP issues a positive opinion regarding renewal of the marketing authorization, and the EC ratifies such determination, the Company would expect to capitalize inventory and commence the expensing of cost of goods sold. Revenue Recognition The Company recognizes revenue when amounts are realized or realizable and earned. Revenue is considered realizable and earned when the following criteria are met: (1) persuasive evidence of an arrangement exists; (2) delivery has occurred or services have been rendered; (3) the price is fixed or determinable; and (4) collection of the amounts due are reasonably assured. Net Product Sales The Company’s net product sales have consisted solely of sales of Translarna for the treatment of nmDMD in territories outside of the U.S. The Company began recognizing revenue for payments received under the reimbursed EAPs for Translarna in nmDMD patients in select countries in the third quarter of 2014. The Company has now established a pattern of collectability and, since January 2015, the Company recognizes revenue from product sales when there is persuasive evidence that an arrangement exists, title to product and associated risk of loss has passed to the customer, the price is fixed or determinable, collectability is reasonably assured and the Company has no further performance obligations in accordance with Financial Accounting Standards Board (“FASB”) Accounting Standards Codification (“ASC”) Subtopic 605-15, Revenue Recognition—Products. The Company has recorded revenue on sales where Translarna is available either on a commercial basis or through a reimbursed EAP program. Orders for Translarna are generally received from hospital and retail pharmacies and, in some cases, one of the Company’s third-party partner distributors. The Company’s third-party partner distributors act as intermediaries between the Company and end users and do not typically stock significant quantities of Translarna. The ultimate payor for Translarna is typically a government authority or institution or a third-party health insurer. The Company records revenue net of estimated third-party discounts and rebates. Allowances are recorded as a reduction of revenue at the time revenues from product sales are recognized. These allowances are adjusted to reflect known changes in factors and may impact such allowances in the quarter those changes are known. Collaboration and Grant Revenue The terms of these agreements typically include payments to the Company of one or more of the following: nonrefundable, upfront license fees; milestone payments; research funding and royalties on future product sales. In addition, the Company generates service revenue through agreements that generally provide for fees for research and development services and may include additional payments upon achievement of specified events. The Company evaluates all contingent consideration earned, such as a milestone payment, using the criteria as provided by FASB ASC 605-28, Revenue Recognition—Milestone Method. At the inception of a collaboration arrangement, the Company evaluates if a milestone payment is substantive. The criteria requires that (1) the Company determines if the milestone is commensurate with either its performance to achieve the milestone or the enhancement of value resulting from our activities to achieve the milestone; (2) the milestone be related to past performance; and (3) the milestone be reasonable relative to all deliverable and payment terms of the collaboration arrangement. If these criteria are met then the contingent milestones can be considered a substantive milestone and will be recognized as revenue in the period that the milestone is achieved. The Company recognizes royalties as earned in accordance with the terms of various research and collaboration agreements. If not substantive, the contingent consideration is allocated to the existing units of accounting based on relative selling price and recognized following the same basis previously established for the associated unit of accounting. The Company recognizes revenue for reimbursements of research and development costs under collaboration agreements as the services are performed. The Company records these reimbursements as revenue and not as a reduction of research and development expenses as the Company has the risks and rewards as the principal in the research and development activities. Allowance for doubtful accounts The Company maintains an allowance for estimated losses resulting from the inability of its customers to make required payments. The Company estimates uncollectible amounts based upon current customer receivable balances, the age of customer receivable balances, the customer’s financial condition and current economic trends. The allowance for doubtful accounts was $0.4 million as of September 30, 2016 and $0 as of December 31, 2015. Recently issued accounting standards In May 2014, the FASB issued Accounting Standards Update (ASU) No. 2014-9, “Revenue from Contracts with Customers (Topic 606)”. ASU No. 2014-9 will eliminate transaction- and industry-specific revenue recognition guidance under current GAAP and replace it with a principle-based approach for determining revenue recognition. ASU No. 2014-9 includes the required steps to achieve the core principle that an entity should recognize revenue to depict the transfer of promised goods or services to customers in an amount that reflects the consideration to which the entity expects to be entitled in exchange for those goods or services. The ASU will also require additional disclosure about the nature, amount, timing and uncertainty of revenue and cash flows arising from customer contracts, including significant judgments and changes in judgments and assets recognized from costs incurred to obtain or fulfill a contract. With the issuance of ASU No. 2015-14 in August 2015, the FASB deferred the effective date of the revenue recognition guidance to reporting periods beginning after December 15, 2017. Early adoption of the standard is permitted but not before the original effective date, which was for reporting periods beginning after December 15, 2016. With the issuance of ASU No. 2016-8 in March 2016 and ASU No. 2016-10 in April 2016, the FASB further amended guidance on recording revenue on a gross versus a net basis and on identifying performance obligations and licensing, respectively. The Company expects to adopt this guidance when effective and continues to evaluate the effect that the updated standard, as well as additional amendments, may have on its consolidated financial statements and accompanying notes. In August 2014, the FASB issued ASU 2014-15, “Presentation of Financial Statements—Going Concern (Subtopic 205-40): Disclosure of Uncertainties about an Entity’s Ability to Continue as a Going Concern”, which defines management’s responsibility to assess an entity’s ability to continue as a going concern, and to provide related footnote disclosures if there is substantial doubt about its ability to continue as a going concern. The pronouncement is effective for annual reporting periods ending after December 15, 2016 with early adoption permitted. The adoption of this guidance is not expected to have a significant impact on the Company’s financial statements. In April 2015, the FASB issued ASU No. 2015-3, “Interest—Imputation of Interest (Subtopic 835-30): Simplifying the Presentation of Debt Issuance Costs topic of the Codification”. This standard provides a simplified presentation of debt issuance costs and requires that debt issuance costs related to a recognized debt liability to be presented on the balance sheet as a direct deduction from the carrying amount of that debt liability, consistent with debt discounts. The standard is effective for public companies for annual periods beginning after December 15, 2015. The Company adopted the guidance on January 1, 2016 on a retrospective basis and reclassed $2.8 million from “Deposits and other assets” to “Long-term debt” on the balance sheet as of December 31, 2015. The Company’s unamortized debt issuance cost at September 30, 2016 was $2.5 million which is included within “Long-term debt” on the consolidated balance sheet. In November 2015, the FASB issued ASU No. 2015-17, “Income Taxes (Topic 740): Balance Sheet Classification of Deferred Taxes”. This standard requires all deferred tax assets and liabilities to be classified as non-current on the balance sheet instead of separating deferred taxes into current and non-current amounts. In addition, valuation allowance allocations between current and non-current deferred tax assets are no longer required because those allowances also will be classified as non-current. This standard is effective for public companies for annual periods beginning after December 15, 2016. Earlier application is permitted as of the beginning of an interim or annual reporting period. The Company’s deferred tax assets is provided with full valuation allowance as of September 30, 2016 . As such, the Company does not expect that this standard will have a significant impact upon adoption. In January 2016, the FASB issued ASU No. 2016-1, “Financial Instruments - Overall (Subtopic 825-10): Recognition and Measurement of Financial Assets and Financial Liabilities”. This standard enhances the reporting model for financial instruments, which includes amendments to address aspects of recognition, measurement, presentation and disclosure. The new guidance affects all reporting organizations (whether public or private) that hold financial assets or owe financial liabilities. ASU 2016-1 is effective for years beginning after December 15, 2017, including interim periods within those fiscal years. The Company expects to adopt this guidance when effective and is currently assessing what effect the adoption of ASU No. 2016-1 will have on its consolidated financial statements and accompanying notes. In February 2016, the FASB issued ASU No. 2016-2, “Leases (Topic 842)”. This standard will require organizations that lease assets with lease terms of more than 12 months to recognize assets and liabilities for the rights and obligations created by those leases on their balance sheets. The ASU will also require new qualitative and quantitative disclosures to help investors and other financial statement users better understand the amount, timing, and uncertainty of cash flows arising from leases. The standard is effective for public companies for fiscal years, and interim periods within those fiscal years, beginning after December 15, 2018, with early adoption permitted. The Company expects to adopt this guidance when effective and is currently assessing what effect the adoption of ASU No. 2016-2 will have on its consolidated financial statements and accompanying notes. In March 2016, the FASB issued ASU No. 2016-9, “Compensation—Stock Compensation (Topic 718): Improvements to Employee Share-Based Payment Accounting”. This standard requires the recognition of all income tax effects of awards in the income statement when the awards vest or are settled, with Additional Paid in Capital (APIC) pools to be eliminated. In addition, the standard will increase the amount an employer can withhold to cover income taxes on awards and still qualify for the exception to liability classification for shares used to satisfy the employer’s statutory income tax withholding obligation as well as allowing companies to elect whether to account for forfeitures of share-based payments by recognizing forfeitures of awards as they occur or estimating the number of awards expected to be forfeited and adjusting the estimate when it is likely to change, as is currently required. This standard is effective for public companies for fiscal years beginning after December 15, 2016 and interim periods within those years, with early adoption permitted but only if all of the guidance is adopted in the same period. The Company expects to adopt this guidance when effective and is currently assessing what effect the adoption of ASU No. 2016-9 will have on its consolidated financial statements and accompanying notes. In June 2016, the FASB issued ASU No. 2016-13, “Financial Instruments — Credit Losses (Topic 326): Measurement of Credit Losses on Financial Instruments”. This standard requires financial assets measured at amortized cost basis to be presented at the net amount expected to be collected. This standard is effective for public companies who are SEC filers for fiscal years beginning after December 15, 2019, including interim periods within those years. The Company expects to adopt this guidance when effective and is assessing what effect the adoption of ASU 2016-13 will have on its consolidated financial statements and accompanying notes. In August 2016, the FASB issued ASU No. 2016-15, “Statement of Cash Flows (Topic 230): Classification of Certain Cash Receipts and Cash Payments”. This standard clarifies the presentation of certain specific cash flow issues in the Statement of cash flows. The standard is effective for public companies for fiscal years, and interim periods within those fiscal years, beginning after December 15, 2017, with early adoption permitted. The adoption of this guidance is not expected to have a significant impact on the Company’s consolidated financial statements.

Fair value of financial instrum

Fair value of financial instruments and marketable securities	9 Months Ended
	Sep. 30, 2016
Fair Value Disclosures [Abstract]
Fair value of financial instruments and marketable securities	Fair value of financial instruments and marketable securities The Company follows the fair value measurement rules, which provides guidance on the use of fair value in accounting and disclosure for assets and liabilities when such accounting and disclosure is called for by other accounting literature. These rules establish a fair value hierarchy for inputs to be used to measure fair value of financial assets and liabilities. This hierarchy prioritizes the inputs to valuation techniques used to measure fair value into three levels: Level 1 (highest priority), Level 2, and Level 3 (lowest priority). · Level 1—Unadjusted quoted prices in active markets for identical assets or liabilities that the Company has the ability to access at the balance sheet date. · Level 2—Inputs other than quoted prices included within Level 1 that are observable for the asset or liability, either directly or indirectly. Level 2 inputs include quoted prices for similar assets and liabilities in active markets, quoted prices for identical or similar assets or liabilities in markets that are not active, inputs other than quoted prices that are observable for the asset or liability (i.e., interest rates, yield curves, etc.), and inputs that are derived principally from or corroborated by observable market data by correlation or other means (market corroborated inputs). · Level 3—Inputs are unobservable and reflect the Company’s assumptions as to what market participants would use in pricing the asset or liability. The Company develops these inputs based on the best information available. Cash equivalents and investments are reflected in the accompanying financial statements at fair value. The carrying amount of grant and collaboration receivables, accounts payable and accrued expenses, and debt approximates fair value due to the short-term nature of those instruments. Fair value of certain marketable securities is based upon market prices using quoted prices in active markets for identical assets quoted on the last day of the period. In establishing the estimated fair value of the remaining investments, the Company used the fair value as determined by its investment advisors using observable inputs other than quoted prices. The Company reviews its investments on a periodic basis for other-than-temporary impairments. This review is subjective, as it requires management to evaluate whether an event or change in circumstances has occurred in that period that may have a significant adverse effect on the fair value of the investment. The following represents the fair value using the hierarchy described above for the Company’s financial assets and liabilities that are required to be measured at fair value on a recurring basis as of September 30, 2016 and December 31, 2015 : September 30, 2016 Total Quoted prices Significant Significant Marketable securities $ 198,052 $ — $ 198,052 $ — Warrant liability $ 4 $ — $ — $ 4 Stock appreciation rights liability $ 838 $ — $ — $ 838 December 31, 2015 Total Quoted prices in active markets for identical assets (level 1) Significant other observable inputs (level 2) Significant unobservable inputs (level 3) Marketable securities $ 280,903 $ — $ 280,903 $ — Warrant Liability $ 48 $ — $ — $ 48 Stock appreciation rights liability $ — $ — $ — $ — No transfers of assets between Level 1 and Level 2 of the fair value measurement hierarchy occurred during the periods ended September 30, 2016 and December 31, 2015 . The following is a summary of marketable securities accounted for as available-for-sale securities at September 30, 2016 and December 31, 2015 : September 30, 2016 Amortized Cost Gross Unrealized Fair Value Gains Losses Commercial paper $ 17,935 $ 53 $ — $ 17,988 Corporate debt securities 166,119 110 (109 ) 166,120 Government obligations 13,936 8 — 13,944 $ 197,990 $ 171 $ (109 ) $ 198,052 December 31, 2015 Amortized Cost Gross Unrealized Fair Value Gains Losses Commercial paper $ 26,877 $ 80 $ — $ 26,957 Corporate debt securities 226,959 — (640 ) 226,319 Government obligations 27,656 3 (32 ) 27,627 $ 281,492 $ 83 $ (672 ) $ 280,903 At September 30, 2016 and December 31, 2015 , the Company held securities with an unrealized loss position that were not considered to be other-than-temporarily impaired as the Company has the ability to hold such investments until recovery of their fair value. Unrealized gains and losses are reported as a component of accumulated other comprehensive (loss) income in stockholders’ equity. As of September 30, 2016 and December 31, 2015 , the Company did not have any realized gains/losses from the sale of marketable securities. Marketable securities on the balance sheet at September 30, 2016 and December 31, 2015 mature as follows: September 30, 2016 Less Than 12 Months More Than 12 Months Commercial paper $ 17,988 $ — Corporate debt securities 132,009 34,111 Government obligations 13,944 — Total Marketable securities $ 163,941 $ 34,111 December 31, 2015 Less Than 12 Months More Than 12 Months Commercial paper $ 26,957 $ — Corporate debt securities 140,831 85,488 Government obligations 18,994 8,633 Total Marketable securities $ 186,782 $ 94,121 The Company classifies all of its securities as current as they are all available for sale and are available for current operations. Level 3 valuation The warrant liability is classified in Other long-term liabilities on the Company’s consolidated balance sheets. The warrant liability is marked-to-market each reporting period with the change in fair value recorded as a gain or loss within Other expense, net, on the Company’s consolidated statements of operations until the warrants are exercised, expire or other facts and circumstances lead the warrant liability to be reclassified as an equity instrument. The fair value of the warrant liability is determined at each reporting period by utilizing the Black-Scholes option pricing model. The stock appreciation rights (SARs) liability is classified in Other long-term liabilities on the Company’s consolidated balance sheets. The SARs liability is marked-to-market each reporting period with the change in fair value recorded as compensation expense on the Company’s consolidated statements of operations until the SARS vest. The fair value of the SARs liability is determined at each reporting period by utilizing the Black-Scholes option pricing model. The table presented below is a summary of changes in the fair value of the Company’s Level 3 valuations for the warrant liability and SARs liability for the period ended September 30, 2016 : Level 3 liabilities Warrants SARs Beginning balance as of December 31, 2015 $ 48 $ — Change in fair value (44 ) 838 Ending balance as of September 30, 2016 $ 4 $ 838 Fair value of the warrant liability is estimated using an option-pricing model, which includes variables such as the expected volatility based on guideline public companies, the stock fair value, and the estimated time to a liquidity event. The significant assumptions used in preparing the option pricing model for valuing the Company’s warrants as of September 30, 2016 include (i) volatility ( 68% — 75% ), (ii) risk free interest rate ( 0.52% — 0.88% ), (iii) strike price ( $128.00 - $2,520.00 ), (iv) fair value of common stock ( $14.01 ), and (v) expected life ( 0.71 — 2.98 years). The significant assumptions used in preparing the option pricing model for valuing the Company’s warrants as of December 31, 2015 include (i) volatility ( 62% - 70% ), (ii) risk free interest rate ( 0.86% — 1.54% ), (iii) strike price ( $128.00 — $2,520.00 ), (iv) fair value of common stock ( $32.40 ), and (v) expected life ( 1.50 — 3.70 years). Fair value of the SARs liability is estimated using an option-pricing model, which includes variables such as the expected volatility based on guideline public companies, the stock fair value, and the estimated time to a liquidity event. The significant assumptions used in preparing the option pricing model for valuing the Company’s SARs as of September 30, 2016 include (i) volatility ( 69% — 75% ), (ii) risk free interest rate ( 0.29% — 0.88% ), (iii) strike price ( $6.76 - $30.86 ), (iv) fair value of common stock ( $14.01 ), and (v) expected life ( 0.26 — 3.26 years).

Other comprehensive income (los

Other comprehensive income (loss) and accumulated other comprehensive items	9 Months Ended
	Sep. 30, 2016
Comprehensive Income (Loss), Net of Tax, Attributable to Parent [Abstract]
Other comprehensive income (loss) and accumulated other comprehensive items	Other comprehensive income (loss) and accumulated other comprehensive items Other comprehensive income (loss) includes changes in equity that are excluded from net income (loss), such as unrealized gains and losses on marketable securities. The following tables summarize other comprehensive income (loss) and the changes in accumulated other comprehensive items for the three and nine months ended September 30, 2016 : Unrealized Gains/(Losses) On Marketable Securities, net of tax Foreign Currency Translation Total Accumulated Other Comprehensive Items Balance at June 30, 2016 $ 29 $ 856 $ 885 Other comprehensive (loss) income before reclassifications (189 ) 60 (129 ) Amounts reclassified from other comprehensive items — — — Other comprehensive (loss) income (189 ) 60 (129 ) Balance at September 30, 2016 $ (160 ) $ 916 $ 756 Unrealized Gains/(Losses) On Marketable Securities, net of tax Foreign Currency Translation Total Accumulated Other Comprehensive Items Balance at December 31, 2015 $ (589 ) $ (611 ) $ (1,200 ) Other comprehensive income before reclassifications 429 1,527 1,956 Amounts reclassified from other comprehensive items — — — Other comprehensive income 429 1,527 1,956 Balance at September 30, 2016 $ (160 ) $ 916 $ 756

Accounts payable and accrued ex

Accounts payable and accrued expenses	9 Months Ended
	Sep. 30, 2016
Payables and Accruals [Abstract]
Accounts payable and accrued expenses	Accounts payable and accrued expenses Accounts payable and accrued expenses at September 30, 2016 and December 31, 2015 consist of the following: September 30, December 31, Employee compensation, benefits, and related accruals $ 8,898 $ 11,187 Consulting and contracted research 13,336 13,753 Professional fees 1,679 2,523 Accounts payable 19,238 11,940 Accrued severance 231 — Other 4,377 5,844 $ 47,759 $ 45,247

Warrants

Warrants	9 Months Ended
	Sep. 30, 2016
Stockholders' Equity Note [Abstract]
Warrants	Warrants All of the Company’s outstanding warrants were classified as liabilities as of September 30, 2016 and December 31, 2015 because they contained non-standard antidilution provisions. The following is a summary of the Company’s outstanding warrants as of September 30, 2016 and December 31, 2015 : Warrant shares Exercise price Expiration Common stock 6,250 $ 128.00 2017 Common stock 7,030 $ 128.00 2019 Common stock 130 $ 2,520.00 2019

Net loss per share

Net loss per share	9 Months Ended
	Sep. 30, 2016
Earnings Per Share [Abstract]
Net loss per share	Net loss per share Basic earnings per share is computed by dividing net income (loss) by the weighted-average number of common shares outstanding. Diluted earnings per share is computed by dividing net income (loss) by the weighted-average number of common shares plus the effect of dilutive potential common shares outstanding during the period. The following tables set forth the computation of basic and diluted net loss per share: Three Months Ended September 30, Nine Months Ended September 30, 2016 2015 2016 2015 Numerator Net loss $ (35,167 ) $ (43,223 ) $ (115,314 ) $ (119,499 ) Denominator Denominator for basic and diluted net loss per share 34,088,741 33,908,853 34,002,952 33,528,833 Net loss per share: Basic and diluted $ (1.03 ) * $ (1.27 ) * $ (3.39 ) * $ (3.56 ) * *In the three and nine months ended September 30, 2016 and 2015, the Company experienced a net loss and therefore did not report any dilutive share impact. The following table shows historical dilutive common share equivalents outstanding, which are not included in the above historical calculation, as the effect of their inclusion is anti-dilutive during each period. As of September 30, 2016 2015 Stock Options 5,832,166 4,788,264 Unvested restricted stock awards and units 272,579 353,135 Total 6,104,745 5,141,399

Stock award plan

Stock award plan	9 Months Ended
	Sep. 30, 2016
Disclosure of Compensation Related Costs, Share-based Payments [Abstract]
Stock award plan	Stock award plan On March 5, 2013, the Company’s Board of Directors approved the 2013 Stock Incentive Plan, which provides for the granting of stock option awards, stock appreciation rights, restricted stock, restricted stock units and other stock-based awards in the aggregate of 739,937 shares of common stock. On March 5, 2013, the Board approved a grant of 735,324 shares of restricted stock and 4,613 stock options. There are no additional shares available for issuance under this plan. In May 2013, the Company’s Board of Directors and stockholders increased by 2,500,000 the number of shares authorized under the 2009 Equity and Long Term Incentive Plan, which provides for the granting of stock option awards, restricted stock awards, and other stock-based and cash-based awards. In May 2013, the Company’s Board of Directors and stockholders approved the 2013 Long Term Incentive Plan, which became effective upon the closing of the Company’s IPO. The 2013 Long Term Incentive Plan provides for the grant of incentive stock options, nonstatutory stock options, restricted stock awards and other stock-based awards. The number of shares of common stock reserved for issuance under the 2013 Long Term Incentive Plan is the sum of (1) 122,296 shares of common stock available for issuance under the Company’s 2009 Equity and Long Term Incentive Plan and 2013 Stock Incentive Plan, (2) the number of shares (up to 3,040,444 shares) equal to the sum of the number of shares of common stock subject to outstanding awards under the Company’s 1998 Employee, Director and Consultant Stock Option Plan, 2009 Equity and Long Term Incentive Plan and 2013 Stock Incentive Plan that expire, terminate or are otherwise surrendered, cancelled, forfeited or repurchased by the Company at their original issuance price pursuant to a contractual repurchase right plus (3) an annual increase, to be added on the first day of each fiscal year until the expiration of the 2013 Long Term Incentive Plan, equal to the lowest of 2,500,000 shares of common stock, 4% of the number of shares of common stock outstanding on the first day of the fiscal year and an amount determined by the Company’s Board of Directors. As of September 30, 2016 , awards for 345,719 shares of common stock are available for issuance. From January 1, 2016 through September 30, 2016 , the Company issued a total of 1,440,445 stock options to various employees. Of those, 116,000 were inducement grants for non-statutory stock options. The inducement grant awards were made pursuant to the NASDAQ inducement grant exception as a material component of our new hires’ employment compensation and not under the 2013 Long Term Incentive Plan. A summary of stock option activity is as follows: Number of Weighted- Weighted- Aggregate (in Outstanding at December 31, 2015 4,826,477 $ 37.20 Granted 1,440,445 $ 28.55 Exercised (85,325 ) $ 10.85 Forfeited/Cancelled (349,431 ) $ 46.77 Outstanding at September 30, 2016 5,832,166 $ 35.03 8.01 years $ 4,132 Vested or Expected to vest at September 30, 2016 3,032,483 $ 35.79 8.50 years $ 1,200 Exercisable at September 30, 2016 2,613,982 $ 34.08 7.38 years $ 2,867 The fair value of grants made in the nine months ended September 30, 2016 was contemporaneously estimated on the date of grant using the following assumptions: Nine months ended Risk-free interest rate 1.30% — 2.24% Expected volatility 67%—78% Expected term 5.05– 10.00 years The Company assumed no expected dividends for all grants. The weighted average grant date fair value of options granted during the nine month period ended September 30, 2016 was $17.67 per share. The Company uses the “simplified method” to determine the expected term of options. Under this method, the expected term represents the average of the vesting period and the contractual term. The expected volatility of share options was estimated based on a historical volatility analysis of peers that were similar to the Company with respect to industry, stage of life cycle, size, and financial leverage. The risk-free rate of the option is based on U.S. Government Securities Treasury Constant Maturities yields at the date of grant for a term similar to the expected term of the option. Restricted Stock Awards —Restricted stock awards are granted subject to certain restrictions, including in some cases service or time conditions (restricted stock). The grant-date fair value of restricted stock awards, which has been determined based upon the market value of the Company’s shares on the grant date, is expensed over the vesting period. Restricted Stock Units —Restricted stock units are granted subject to certain restrictions, including in some cases service or time conditions (restricted stock). The grant-date fair value of restricted stock units, which has been determined based upon the market value of the Company’s shares on the grant date, is expensed over the vesting period. The following table summarizes information on the Company’s restricted stock awards and units: Restricted Stock Awards and Units Number of Weighted January 1, 2016 344,335 $ 10.85 Granted 141,185 $ 30.86 Vested (163,635 ) $ 10.85 Forfeited (49,306 ) $ 18.69 Unvested at September 30, 2016 272,579 $ 19.80 Stock Appreciation Rights —Stock appreciation rights (SARs) entitle the holder to receive, upon exercise, an amount of the Company's common stock or cash (or a combination thereof) determined by reference to appreciation, from and after the date of grant, in the fair market value of a share of the Company's common stock over the measurement price based on the exercise date. In May 2016, a total of 897,290 SARs were granted to non-executive employees (the 2016 SARs). The 2016 SARs will vest annually in equal installments over four years and will be settled in cash on each vest date, requiring the Company to remeasure the SARs at each reporting period until vesting occurs. For the period ending September 30, 2016 , the Company recorded $0.8 million in compensation expense related to the 2016 SARs. Employee Stock Purchase Plan —In June 2016, the Company established an Employee Stock Purchase Plan (“ESPP” or “the Plan”) for certain eligible employees. The Plan is administered by the Company’s Board of Directors or a committee appointed by the Board. The total number of shares available for purchase under the Plan is one million shares of the Company’s common stock. Employees may participate over a six -month period through payroll withholdings and may purchase, at the end of the six -month period, the Company’s common stock at a purchase price of at least 85% of the closing price of a share of the Company’s common stock on the first business day of the offering period or the closing price of a share of the Company’s common stock on the last business day of the offering period, whichever is lower. No participant will be granted a right to purchase the Company’s common stock under the Plan if such participant would own more than 5% of the total combined voting power of the Company or any subsidiary of the Company after such purchase. For the period ending September 30, 2016 , the Company recorded $0.1 million in compensation expense related to the ESPP. The Company recorded share-based compensation expense in the statement of operations related to incentive stock options, nonstatutory stock options, restricted stock awards, restricted stock units and the ESPP as follows: Three Months Ended September 30, Nine Months Ended September 30, 2016 2015 2016 2015 Research and development $ 4,319 $ 3,828 $ 12,734 $ 12,452 Selling, general and administrative 4,640 4,226 13,876 13,678 Total $ 8,959 $ 8,054 $ 26,610 $ 26,130 As of September 30, 2016 there was approximately $70.8 million of total unrecognized compensation cost related to unvested share-based compensation arrangements granted under the 2009 Equity and Long Term Incentive Plan, the 2013 Long Term Incentive Plan and equity awards made pursuant to the NASDAQ inducement grant exception for new hires. This cost is expected to be recognized as share-based compensation expense over the weighted average remaining service period of approximately 2.32 years.

Convertible Senior Notes

Convertible Senior Notes	9 Months Ended
	Sep. 30, 2016
Debt Disclosure [Abstract]
Convertible Senior Notes	Convertible Senior Notes In August 2015, the Company issued, at par value, $150.0 million aggregate principal amount of 3.0% convertible senior notes due 2022 (the Convertible Notes). The Convertible Notes bear cash interest at a rate of 3.0% per year, payable semi-annually on February 15 and August 15 of each year, beginning on February 15, 2016. The Convertible Notes will mature on August 15, 2022, unless earlier repurchased or converted. The net proceeds to the Company from the offering were $145.4 million after deducting the initial purchasers’ discounts and commissions and the offering expenses payable by the Company. The Convertible Notes are governed by an indenture (the Convertible Notes Indenture) with U.S Bank National Association as trustee (the Convertible Notes Trustee). Holders may convert their Convertible Notes at their option at any time prior to the close of business on the business day immediately preceding February 15, 2022 only under the following circumstances: · during any calendar quarter commencing on or after September 30, 2015 (and only during such calendar quarter), if the last reported sale price of the Company’s common stock for at least 20 trading days (whether or not consecutive) during a period of 30 consecutive trading days ending on the last trading day of the immediately preceding calendar quarter is greater than or equal to 130% of the conversion price on each applicable trading day; · during the five business day period after any five consecutive trading day period (the “measurement period”) in which the trading price (as defined in the Convertible Notes Indenture) per $1,000 principal amount of Convertible Notes for each trading day of the measurement period was less than 98% of the product of the last reported sale price of the Company’s common stock and the conversion rate on each such trading day; · during any period after the Company has issued notice of redemption until the close of business on the scheduled trading day immediately preceding the relevant redemption date; or · upon the occurrence of specified corporate events On or after February 15, 2022, until the close of business on the business day immediately preceding the maturity date, holders may convert their Convertible Notes at any time, regardless of the foregoing circumstances. Upon conversion, the Company will pay cash up to the aggregate principal amount of the Convertible Notes to be converted and deliver shares of its common stock in respect of the remainder, if any, of its conversion obligation in excess of the aggregate principal amount of Convertible Notes being converted. The conversion rate for the Convertible Notes was initially, and remains, 17.7487 shares of the Company’s common stock per $1,000 principal amount of the Convertible Notes, which is equivalent to an initial conversion price of approximately $56.34 per share of the Company’s common stock. The Company may not redeem the Convertible Notes prior to August 20, 2018. The Company may redeem for cash all or any portion of the Convertible Notes, at its option, on or after August 20, 2018 if the last reported sale price of its common stock has been at least 130% of the conversion price then in effect on the last trading day of, and for at least 19 other trading days (whether or not consecutive) during, any 30 consecutive trading day period ending on, and including, the trading day immediately preceding the date on which the Company provides notice of redemption, at a redemption price equal to 100% of the principal amount of the Convertible Notes to be redeemed, plus accrued and unpaid interest to, but excluding, the redemption date. No sinking fund is provided for the Convertible Notes, which means that the Company is not required to redeem or retire the Convertible Notes periodically. If the Company undergoes a “fundamental change” (as defined in the Indenture governing the Convertible Notes Indenture), subject to certain conditions, holders of the Convertible Notes may require the Company to repurchase for cash all or part of their Convertible Notes at a repurchase price equal to 100% of the principal amount of the Convertible Notes to be repurchased, plus accrued and unpaid interest to, but excluding, the fundamental change repurchase date. The Convertible Notes Indenture contains customary events of default with respect to the Convertible Notes, including that upon certain events of default (including the Company’s failure to make any payment of principal or interest on the Convertible Notes when due and payable) occurring and continuing, the Convertible Notes Trustee by notice to the Company, or the holders of at least 25% in principal amount of the outstanding Convertible Notes by notice to the Company and the Convertible Notes Trustee, may, and the Convertible Notes Trustee at the request of such holders (subject to the provisions of the Convertible Notes Indenture) shall, declare 100% of the principal of and accrued and unpaid interest, if any, on all the Convertible Notes to be due and payable. In case of certain events of bankruptcy, insolvency or reorganization, involving the Company or a significant subsidiary, 100% of the principal of and accrued and unpaid interest on the Convertible Notes will automatically become due and payable. Upon such a declaration of acceleration, such principal and accrued and unpaid interest, if any, will be due and payable immediately. The Company accounts for the Convertible Notes as a liability and equity component where the carrying value of the liability component will be valued based on a similar instrument. In accounting for the issuance of the Convertible Notes, the Company separated the Convertible Notes into liability and equity components. The carrying amount of the liability component was calculated by measuring the fair value of a similar liability that does not have an associated convertible feature. The carrying amount of the equity component representing the conversion option was determined by deducting the fair value of the liability component from the par value of the Convertible Notes as a whole. The excess of the principal amount of the liability component over its carrying amount, referred to as the debt discount, is amortized to interest expense over the seven -year term of the Convertible Notes. The equity component is not re-measured as long as it continues to meet the conditions for equity classification. In accounting for the transaction costs related to the issuance of the Convertible Notes, the Company allocated the total costs incurred to the liability and equity components of the Convertible Notes based on their relative values. Transaction costs attributable to the liability component are amortized to interest expense over the seven -year term of the Convertible Notes, and transaction costs attributable to the equity component are netted with the equity components in stockholders’ equity. Additionally, the Company initially recorded a net deferred tax liability of $22.3 million in connection with the Notes. The Convertible Notes consist of the following: Liability component September 30, 2016 December 31, 2015 Principal $ 150,000 $ 150,000 Less: Debt issuance costs (2,536 ) (2,760 ) Less: Debt discount, net(1) (50,905 ) (55,392 ) Net carrying amount $ 96,559 $ 91,848 (1) Included in the consolidated balance sheets within convertible senior notes (due 2022) and amortized to interest expense over the remaining life of the Convertible Notes using the effective interest rate method. The fair value of the Convertible Notes was approximately $89.2 million as of September 30, 2016 . The Company estimates the fair value of its Convertible Notes utilizing market quotations for debt that have quoted prices in active markets. As of September 30, 2016 , the remaining contractual life of the Convertible Notes is approximately 5.9 years. The following table sets forth total interest expense recognized related to the Convertible Notes: Three Months Ended September 30, Nine Months Ended September 30, 2016 2015 2016 2015 Contractual interest expense $ 1,131 $ 584 $ 3,372 $ 584 Amortization of debt issuance costs 77 37 224 37 Amortization of debt discount 1,546 736 4,487 736 Total $ 2,754 $ 1,357 $ 8,083 $ 1,357 Effective interest rate of the liability component 11 % 11 % 11 % 11 %

Restructuring

Restructuring	9 Months Ended
	Sep. 30, 2016
Restructuring Charges [Abstract]
Restructuring	Restructuring In March 2016, the Company commenced implementation of a reorganization of its operations intended to improve efficiency and better align the Company’s costs and employment structure with its strategic plans. The Company completed its reorganization in June 2016 and recorded a one-time charge of $2.5 million for the nine month period ended September 30, 2016 . The total $2.5 million in one-time charges is related to work-force reduction, recorded in research and development and selling, general and administrative expenses in the accompanying statement of operations. Balance as of Expenses, Cash Balance as of 2016 workforce reduction $ 995 $ 33 $ (797 ) $ 231

Commitments and contingencies

Commitments and contingencies	9 Months Ended
	Sep. 30, 2016
Commitments and Contingencies Disclosure [Abstract]
Commitments and contingencies	Commitments and contingencies Under various agreements, the Company will be required to pay royalties and milestone payments upon the successful development and commercialization of products. The Company has entered into funding agreements with The Wellcome Trust Limited (Wellcome Trust) for the research and development of small molecule compounds. To the extent that the Company develops and commercializes program intellectual property on a for-profit basis, it may become obligated to pay to Wellcome Trust development and regulatory milestone payments of up to an aggregate of $68.9 million and single-digit royalties on sales of any research program product. The Company’s obligation to pay such royalties would continue on a country-by-country basis until the longer of the expiration of the last patent in the program intellectual property in such country covering the research program product and the expiration of market exclusivity of such product in such country. The Company’s first such milestone payment of $0.8 million payable to Wellcome Trust occurred in the second quarter of 2016. The Company has also entered into a collaboration agreement with the SMA Foundation. The Company may become obligated to pay the SMA Foundation single- digit royalties on worldwide net product sales of any collaboration product that we successfully develop and subsequently commercialize or, if we outlicense rights to a collaboration product, a specified percentage of certain payments we receive from our licensee. The Company is not obligated to make such payments unless and until annual sales of a collaboration product exceed a designated threshold. The Company’s obligation to make such payments would end upon our payment to the SMA Foundation of a specified amount. The Company has employment agreements with certain employees which require the funding of a specific level of payments, if certain events, such as a change in control or termination without cause, occur.

Subsequent events

Subsequent events	9 Months Ended
	Sep. 30, 2016
Subsequent Events [Abstract]
Subsequent events	Subsequent events The Company has evaluated all subsequent events and transactions through the filing date. There were no material events that impacted the unaudited consolidated financial statements or disclosures.

Summary of significant accoun19

Summary of significant accounting policies (Policies)	9 Months Ended
	Sep. 30, 2016
Accounting Policies [Abstract]
Basis of Presentation	Basis of Presentation The accompanying financial information as of September 30, 2016 and for the three and nine months ended September 30, 2016 and 2015 has been prepared by the Company, without audit, pursuant to the rules and regulations of the SEC. Certain information and footnote disclosures normally included in financial statements prepared in accordance with generally accepted accounting principles in the United States (GAAP) have been condensed or omitted pursuant to such rules and regulations. These interim financial statements should be read in conjunction with the Company’s audited financial statements as of December 31, 2015 and notes thereto included in the 2015 Form 10-K. In the opinion of management, the unaudited financial information as of September 30, 2016 and for the three and nine months ended September 30, 2016 and 2015 reflects all adjustments, which are normal recurring adjustments, necessary to present a fair statement of financial position, results of operations and cash flows. The results of operations for the three and nine month periods ended September 30, 2016 are not necessarily indicative of the results to be expected for the year ended December 31, 2016 or for any other interim period or for any other future year.
Use of estimates	Use of estimates The preparation of financial statements in conformity with GAAP requires management to make estimates and assumptions that affect the amounts reported in the financial statements and accompanying notes. Significant estimates in these consolidated financial statements have been made in connection with the calculation of net product sales, certain accruals related to the Company’s research and development expenses, stock-based compensation, valuation procedures for the convertible notes, allowance for doubtful accounts and the provision for or benefit from income taxes. Actual results could differ from those estimates. Changes in estimates are reflected in reported results in the period in which they become known.
Inventories and cost of product revenue	Inventories and cost of product revenue In 2014, the Company was notified that the European Commission, or EC, granted marketing authorization for Translarna for the treatment of nmDMD in ambulatory patients aged five years and older. The conditional marketing authorization allows the Company to market Translarna for the treatment of nmDMD in the 31 member states of European Economic Area. The launch in these countries is on a country by country basis. This marketing authorization is subject to annual review and renewal by the EC following reassessment by the European Medicines Agency, or EMA, of the risk benefit balance of the authorization, which the Company refers to as the annual EMA reassessment. The authorization was further conditioned on the Company’s submission of the final report, including additional efficacy and safety data, from ACT DMD and the Company’s ability to implement measures, including pharmacovigilance plans that are detailed in the risk management plan for Translarna that was submitted to EMA. In January 2016, the Company submitted the final ACT DMD report to the EMA. The Company made this submission as a type II variation request that sought to have this initial condition to its marketing authorization removed and a full marketing authorization granted. In February 2016, the Company also submitted a marketing authorization renewal request with the EMA. The annual EMA reassessment process related to the Company's 2016 marketing authorization request is still ongoing and, as of the time of this filing, renewal has not been granted. The Company expects that the EMA's CHMP will adopt an opinion as to whether to renew the Company's marketing authorization for Translarna for the treatment of nmDMD by the end of 2016. Pursuant to applicable regulations, the Company expects that its current marketing authorization status (which was last renewed by the European Commission in the third quarter of 2015) will remain valid while the 2016 annual EMA reassessment is ongoing and until it is concluded with an opinion from the European Commission with respect to renewal of the marketing authorization. In the event that the Company's marketing authorization renewal request is granted, the Company plans to seek to renew the marketing authorization on an annual basis until any further obligations or conditions that may be placed by the EC on the marketing authorization have been fulfilled and the approval is converted from a conditional approval into a full approval. If the Company fails to satisfy such further obligations or conditions, or if it is determined that the balance of risks and benefits of using Translarna changes materially, the EC could, at the EMA’s recommendation, vary, suspend, withdraw or refuse to renew the marketing authorization for Translarna or require additional clinical trials. There continues to be substantial risk that regulators could suspend or not renew the Company’s marketing authorization in the future. As such, as of the date of this filing, the Company has not capitalized inventory given the near-term uncertainty with respect to the long-term utilization of Translarna finished product for commercial use. Had the Company capitalized as inventory all of the its Translarna product that is available for commercial sale on hand as of September 30, 2016 , the value of that inventory would have been approximately $1.3 million . In addition, had the Company expensed the cost of Translarna product sold as a cost of sales, the gross profit margin would have been greater than 90% , which the Company believes is consistent with the cost of producing small molecule therapeutics for orphan drug diseases in the pharmaceutical industry. The Company will continue to assess the appropriateness of inventory capitalization based on the outcome of applicable regulatory determinations, including the pending CHMP opinion regarding the potential annual renewal of our marketing authorization in the EEA, which is expected to be issued in 2016 and followed by ratification by the EC in early 2017. In the event the CHMP issues a positive opinion regarding renewal of the marketing authorization, and the EC ratifies such determination, the Company would expect to capitalize inventory and commence the expensing of cost of goods sold.
Revenue Recognition	Revenue Recognition The Company recognizes revenue when amounts are realized or realizable and earned. Revenue is considered realizable and earned when the following criteria are met: (1) persuasive evidence of an arrangement exists; (2) delivery has occurred or services have been rendered; (3) the price is fixed or determinable; and (4) collection of the amounts due are reasonably assured. Net Product Sales The Company’s net product sales have consisted solely of sales of Translarna for the treatment of nmDMD in territories outside of the U.S. The Company began recognizing revenue for payments received under the reimbursed EAPs for Translarna in nmDMD patients in select countries in the third quarter of 2014. The Company has now established a pattern of collectability and, since January 2015, the Company recognizes revenue from product sales when there is persuasive evidence that an arrangement exists, title to product and associated risk of loss has passed to the customer, the price is fixed or determinable, collectability is reasonably assured and the Company has no further performance obligations in accordance with Financial Accounting Standards Board (“FASB”) Accounting Standards Codification (“ASC”) Subtopic 605-15, Revenue Recognition—Products. The Company has recorded revenue on sales where Translarna is available either on a commercial basis or through a reimbursed EAP program. Orders for Translarna are generally received from hospital and retail pharmacies and, in some cases, one of the Company’s third-party partner distributors. The Company’s third-party partner distributors act as intermediaries between the Company and end users and do not typically stock significant quantities of Translarna. The ultimate payor for Translarna is typically a government authority or institution or a third-party health insurer. The Company records revenue net of estimated third-party discounts and rebates. Allowances are recorded as a reduction of revenue at the time revenues from product sales are recognized. These allowances are adjusted to reflect known changes in factors and may impact such allowances in the quarter those changes are known. Collaboration and Grant Revenue The terms of these agreements typically include payments to the Company of one or more of the following: nonrefundable, upfront license fees; milestone payments; research funding and royalties on future product sales. In addition, the Company generates service revenue through agreements that generally provide for fees for research and development services and may include additional payments upon achievement of specified events. The Company evaluates all contingent consideration earned, such as a milestone payment, using the criteria as provided by FASB ASC 605-28, Revenue Recognition—Milestone Method. At the inception of a collaboration arrangement, the Company evaluates if a milestone payment is substantive. The criteria requires that (1) the Company determines if the milestone is commensurate with either its performance to achieve the milestone or the enhancement of value resulting from our activities to achieve the milestone; (2) the milestone be related to past performance; and (3) the milestone be reasonable relative to all deliverable and payment terms of the collaboration arrangement. If these criteria are met then the contingent milestones can be considered a substantive milestone and will be recognized as revenue in the period that the milestone is achieved. The Company recognizes royalties as earned in accordance with the terms of various research and collaboration agreements. If not substantive, the contingent consideration is allocated to the existing units of accounting based on relative selling price and recognized following the same basis previously established for the associated unit of accounting. The Company recognizes revenue for reimbursements of research and development costs under collaboration agreements as the services are performed. The Company records these reimbursements as revenue and not as a reduction of research and development expenses as the Company has the risks and rewards as the principal in the research and development activities.
Allowance for doubtful accounts	Allowance for doubtful accounts The Company maintains an allowance for estimated losses resulting from the inability of its customers to make required payments. The Company estimates uncollectible amounts based upon current customer receivable balances, the age of customer receivable balances, the customer’s financial condition and current economic trends.
Recently issued accounting standards	Recently issued accounting standards In May 2014, the FASB issued Accounting Standards Update (ASU) No. 2014-9, “Revenue from Contracts with Customers (Topic 606)”. ASU No. 2014-9 will eliminate transaction- and industry-specific revenue recognition guidance under current GAAP and replace it with a principle-based approach for determining revenue recognition. ASU No. 2014-9 includes the required steps to achieve the core principle that an entity should recognize revenue to depict the transfer of promised goods or services to customers in an amount that reflects the consideration to which the entity expects to be entitled in exchange for those goods or services. The ASU will also require additional disclosure about the nature, amount, timing and uncertainty of revenue and cash flows arising from customer contracts, including significant judgments and changes in judgments and assets recognized from costs incurred to obtain or fulfill a contract. With the issuance of ASU No. 2015-14 in August 2015, the FASB deferred the effective date of the revenue recognition guidance to reporting periods beginning after December 15, 2017. Early adoption of the standard is permitted but not before the original effective date, which was for reporting periods beginning after December 15, 2016. With the issuance of ASU No. 2016-8 in March 2016 and ASU No. 2016-10 in April 2016, the FASB further amended guidance on recording revenue on a gross versus a net basis and on identifying performance obligations and licensing, respectively. The Company expects to adopt this guidance when effective and continues to evaluate the effect that the updated standard, as well as additional amendments, may have on its consolidated financial statements and accompanying notes. In August 2014, the FASB issued ASU 2014-15, “Presentation of Financial Statements—Going Concern (Subtopic 205-40): Disclosure of Uncertainties about an Entity’s Ability to Continue as a Going Concern”, which defines management’s responsibility to assess an entity’s ability to continue as a going concern, and to provide related footnote disclosures if there is substantial doubt about its ability to continue as a going concern. The pronouncement is effective for annual reporting periods ending after December 15, 2016 with early adoption permitted. The adoption of this guidance is not expected to have a significant impact on the Company’s financial statements. In April 2015, the FASB issued ASU No. 2015-3, “Interest—Imputation of Interest (Subtopic 835-30): Simplifying the Presentation of Debt Issuance Costs topic of the Codification”. This standard provides a simplified presentation of debt issuance costs and requires that debt issuance costs related to a recognized debt liability to be presented on the balance sheet as a direct deduction from the carrying amount of that debt liability, consistent with debt discounts. The standard is effective for public companies for annual periods beginning after December 15, 2015. The Company adopted the guidance on January 1, 2016 on a retrospective basis and reclassed $2.8 million from “Deposits and other assets” to “Long-term debt” on the balance sheet as of December 31, 2015. The Company’s unamortized debt issuance cost at September 30, 2016 was $2.5 million which is included within “Long-term debt” on the consolidated balance sheet. In November 2015, the FASB issued ASU No. 2015-17, “Income Taxes (Topic 740): Balance Sheet Classification of Deferred Taxes”. This standard requires all deferred tax assets and liabilities to be classified as non-current on the balance sheet instead of separating deferred taxes into current and non-current amounts. In addition, valuation allowance allocations between current and non-current deferred tax assets are no longer required because those allowances also will be classified as non-current. This standard is effective for public companies for annual periods beginning after December 15, 2016. Earlier application is permitted as of the beginning of an interim or annual reporting period. The Company’s deferred tax assets is provided with full valuation allowance as of September 30, 2016 . As such, the Company does not expect that this standard will have a significant impact upon adoption. In January 2016, the FASB issued ASU No. 2016-1, “Financial Instruments - Overall (Subtopic 825-10): Recognition and Measurement of Financial Assets and Financial Liabilities”. This standard enhances the reporting model for financial instruments, which includes amendments to address aspects of recognition, measurement, presentation and disclosure. The new guidance affects all reporting organizations (whether public or private) that hold financial assets or owe financial liabilities. ASU 2016-1 is effective for years beginning after December 15, 2017, including interim periods within those fiscal years. The Company expects to adopt this guidance when effective and is currently assessing what effect the adoption of ASU No. 2016-1 will have on its consolidated financial statements and accompanying notes. In February 2016, the FASB issued ASU No. 2016-2, “Leases (Topic 842)”. This standard will require organizations that lease assets with lease terms of more than 12 months to recognize assets and liabilities for the rights and obligations created by those leases on their balance sheets. The ASU will also require new qualitative and quantitative disclosures to help investors and other financial statement users better understand the amount, timing, and uncertainty of cash flows arising from leases. The standard is effective for public companies for fiscal years, and interim periods within those fiscal years, beginning after December 15, 2018, with early adoption permitted. The Company expects to adopt this guidance when effective and is currently assessing what effect the adoption of ASU No. 2016-2 will have on its consolidated financial statements and accompanying notes. In March 2016, the FASB issued ASU No. 2016-9, “Compensation—Stock Compensation (Topic 718): Improvements to Employee Share-Based Payment Accounting”. This standard requires the recognition of all income tax effects of awards in the income statement when the awards vest or are settled, with Additional Paid in Capital (APIC) pools to be eliminated. In addition, the standard will increase the amount an employer can withhold to cover income taxes on awards and still qualify for the exception to liability classification for shares used to satisfy the employer’s statutory income tax withholding obligation as well as allowing companies to elect whether to account for forfeitures of share-based payments by recognizing forfeitures of awards as they occur or estimating the number of awards expected to be forfeited and adjusting the estimate when it is likely to change, as is currently required. This standard is effective for public companies for fiscal years beginning after December 15, 2016 and interim periods within those years, with early adoption permitted but only if all of the guidance is adopted in the same period. The Company expects to adopt this guidance when effective and is currently assessing what effect the adoption of ASU No. 2016-9 will have on its consolidated financial statements and accompanying notes. In June 2016, the FASB issued ASU No. 2016-13, “Financial Instruments — Credit Losses (Topic 326): Measurement of Credit Losses on Financial Instruments”. This standard requires financial assets measured at amortized cost basis to be presented at the net amount expected to be collected. This standard is effective for public companies who are SEC filers for fiscal years beginning after December 15, 2019, including interim periods within those years. The Company expects to adopt this guidance when effective and is assessing what effect the adoption of ASU 2016-13 will have on its consolidated financial statements and accompanying notes. In August 2016, the FASB issued ASU No. 2016-15, “Statement of Cash Flows (Topic 230): Classification of Certain Cash Receipts and Cash Payments”. This standard clarifies the presentation of certain specific cash flow issues in the Statement of cash flows. The standard is effective for public companies for fiscal years, and interim periods within those fiscal years, beginning after December 15, 2017, with early adoption permitted. The adoption of this guidance is not expected to have a significant impact on the Company’s consolidated financial statements.

Fair value of financial instr20

Fair value of financial instruments and marketable securities (Tables)	9 Months Ended
	Sep. 30, 2016
Fair Value Disclosures [Abstract]
Schedule of financial assets and liabilities that are required to be measured at fair value on a recurring basis	The following represents the fair value using the hierarchy described above for the Company’s financial assets and liabilities that are required to be measured at fair value on a recurring basis as of September 30, 2016 and December 31, 2015 : September 30, 2016 Total Quoted prices Significant Significant Marketable securities $ 198,052 $ — $ 198,052 $ — Warrant liability $ 4 $ — $ — $ 4 Stock appreciation rights liability $ 838 $ — $ — $ 838 December 31, 2015 Total Quoted prices in active markets for identical assets (level 1) Significant other observable inputs (level 2) Significant unobservable inputs (level 3) Marketable securities $ 280,903 $ — $ 280,903 $ — Warrant Liability $ 48 $ — $ — $ 48 Stock appreciation rights liability $ — $ — $ — $ —
Summary of marketable securities accounted for as available-for-sale securities	The following is a summary of marketable securities accounted for as available-for-sale securities at September 30, 2016 and December 31, 2015 : September 30, 2016 Amortized Cost Gross Unrealized Fair Value Gains Losses Commercial paper $ 17,935 $ 53 $ — $ 17,988 Corporate debt securities 166,119 110 (109 ) 166,120 Government obligations 13,936 8 — 13,944 $ 197,990 $ 171 $ (109 ) $ 198,052 December 31, 2015 Amortized Cost Gross Unrealized Fair Value Gains Losses Commercial paper $ 26,877 $ 80 $ — $ 26,957 Corporate debt securities 226,959 — (640 ) 226,319 Government obligations 27,656 3 (32 ) 27,627 $ 281,492 $ 83 $ (672 ) $ 280,903
Schedule of marketable securities on the balance sheet	Marketable securities on the balance sheet at September 30, 2016 and December 31, 2015 mature as follows: September 30, 2016 Less Than 12 Months More Than 12 Months Commercial paper $ 17,988 $ — Corporate debt securities 132,009 34,111 Government obligations 13,944 — Total Marketable securities $ 163,941 $ 34,111 December 31, 2015 Less Than 12 Months More Than 12 Months Commercial paper $ 26,957 $ — Corporate debt securities 140,831 85,488 Government obligations 18,994 8,633 Total Marketable securities $ 186,782 $ 94,121
Summary of changes in the fair value of the Company's Level 3 valuation for warrant liability and SARs liability	The table presented below is a summary of changes in the fair value of the Company’s Level 3 valuations for the warrant liability and SARs liability for the period ended September 30, 2016 : Level 3 liabilities Warrants SARs Beginning balance as of December 31, 2015 $ 48 $ — Change in fair value (44 ) 838 Ending balance as of September 30, 2016 $ 4 $ 838

Other comprehensive income (l21

Other comprehensive income (loss) and accumulated other comprehensive items (Tables)	9 Months Ended
	Sep. 30, 2016
Comprehensive Income (Loss), Net of Tax, Attributable to Parent [Abstract]
Summary of other comprehensive income (loss) and the changes in accumulated other comprehensive items	The following tables summarize other comprehensive income (loss) and the changes in accumulated other comprehensive items for the three and nine months ended September 30, 2016 : Unrealized Gains/(Losses) On Marketable Securities, net of tax Foreign Currency Translation Total Accumulated Other Comprehensive Items Balance at June 30, 2016 $ 29 $ 856 $ 885 Other comprehensive (loss) income before reclassifications (189 ) 60 (129 ) Amounts reclassified from other comprehensive items — — — Other comprehensive (loss) income (189 ) 60 (129 ) Balance at September 30, 2016 $ (160 ) $ 916 $ 756 Unrealized Gains/(Losses) On Marketable Securities, net of tax Foreign Currency Translation Total Accumulated Other Comprehensive Items Balance at December 31, 2015 $ (589 ) $ (611 ) $ (1,200 ) Other comprehensive income before reclassifications 429 1,527 1,956 Amounts reclassified from other comprehensive items — — — Other comprehensive income 429 1,527 1,956 Balance at September 30, 2016 $ (160 ) $ 916 $ 756

Accounts payable and accrued 22

Accounts payable and accrued expenses (Tables)	9 Months Ended
	Sep. 30, 2016
Payables and Accruals [Abstract]
Schedule of components of accounts payable and accrued expenses	Accounts payable and accrued expenses at September 30, 2016 and December 31, 2015 consist of the following: September 30, December 31, Employee compensation, benefits, and related accruals $ 8,898 $ 11,187 Consulting and contracted research 13,336 13,753 Professional fees 1,679 2,523 Accounts payable 19,238 11,940 Accrued severance 231 — Other 4,377 5,844 $ 47,759 $ 45,247

Warrants (Tables)

Warrants (Tables)	9 Months Ended
	Sep. 30, 2016
Stockholders' Equity Note [Abstract]
Summary of the Company's outstanding warrants	The following is a summary of the Company’s outstanding warrants as of September 30, 2016 and December 31, 2015 : Warrant shares Exercise price Expiration Common stock 6,250 $ 128.00 2017 Common stock 7,030 $ 128.00 2019 Common stock 130 $ 2,520.00 2019

Net loss per share (Tables)

Net loss per share (Tables)	9 Months Ended
	Sep. 30, 2016
Earnings Per Share [Abstract]
Schedule of computation of basic and diluted net loss available to common stockholders	The following tables set forth the computation of basic and diluted net loss per share: Three Months Ended September 30, Nine Months Ended September 30, 2016 2015 2016 2015 Numerator Net loss $ (35,167 ) $ (43,223 ) $ (115,314 ) $ (119,499 ) Denominator Denominator for basic and diluted net loss per share 34,088,741 33,908,853 34,002,952 33,528,833 Net loss per share: Basic and diluted $ (1.03 ) * $ (1.27 ) * $ (3.39 ) * $ (3.56 ) * *In the three and nine months ended September 30, 2016 and 2015, the Company experienced a net loss and therefore did not report any dilutive share impact.
Schedule of historical dilutive common share equivalents outstanding	The following table shows historical dilutive common share equivalents outstanding, which are not included in the above historical calculation, as the effect of their inclusion is anti-dilutive during each period. As of September 30, 2016 2015 Stock Options 5,832,166 4,788,264 Unvested restricted stock awards and units 272,579 353,135 Total 6,104,745 5,141,399

Stock award plan (Tables)

Stock award plan (Tables)	9 Months Ended
	Sep. 30, 2016
Disclosure of Compensation Related Costs, Share-based Payments [Abstract]
Summary of stock option activity	A summary of stock option activity is as follows: Number of Weighted- Weighted- Aggregate (in Outstanding at December 31, 2015 4,826,477 $ 37.20 Granted 1,440,445 $ 28.55 Exercised (85,325 ) $ 10.85 Forfeited/Cancelled (349,431 ) $ 46.77 Outstanding at September 30, 2016 5,832,166 $ 35.03 8.01 years $ 4,132 Vested or Expected to vest at September 30, 2016 3,032,483 $ 35.79 8.50 years $ 1,200 Exercisable at September 30, 2016 2,613,982 $ 34.08 7.38 years $ 2,867
Schedule of assumptions used to estimate fair values of grants made on the date of grant	The fair value of grants made in the nine months ended September 30, 2016 was contemporaneously estimated on the date of grant using the following assumptions: Nine months ended Risk-free interest rate 1.30% — 2.24% Expected volatility 67%—78% Expected term 5.05– 10.00 years
Summary of information on the Company's restricted stock	The following table summarizes information on the Company’s restricted stock awards and units: Restricted Stock Awards and Units Number of Weighted January 1, 2016 344,335 $ 10.85 Granted 141,185 $ 30.86 Vested (163,635 ) $ 10.85 Forfeited (49,306 ) $ 18.69 Unvested at September 30, 2016 272,579 $ 19.80
Schedule of share-based compensation expense recorded in the statement of operations	The Company recorded share-based compensation expense in the statement of operations related to incentive stock options, nonstatutory stock options, restricted stock awards, restricted stock units and the ESPP as follows: Three Months Ended September 30, Nine Months Ended September 30, 2016 2015 2016 2015 Research and development $ 4,319 $ 3,828 $ 12,734 $ 12,452 Selling, general and administrative 4,640 4,226 13,876 13,678 Total $ 8,959 $ 8,054 $ 26,610 $ 26,130

Convertible Senior Notes (Table

Convertible Senior Notes (Tables)	9 Months Ended
	Sep. 30, 2016
Debt Disclosure [Abstract]
Summary of convertible notes	The Convertible Notes consist of the following: Liability component September 30, 2016 December 31, 2015 Principal $ 150,000 $ 150,000 Less: Debt issuance costs (2,536 ) (2,760 ) Less: Debt discount, net(1) (50,905 ) (55,392 ) Net carrying amount $ 96,559 $ 91,848 (1) Included in the consolidated balance sheets within convertible senior notes (due 2022) and amortized to interest expense over the remaining life of the Convertible Notes using the effective interest rate method.
Summary of interest expense recognized related to the Convertible Notes	The following table sets forth total interest expense recognized related to the Convertible Notes: Three Months Ended September 30, Nine Months Ended September 30, 2016 2015 2016 2015 Contractual interest expense $ 1,131 $ 584 $ 3,372 $ 584 Amortization of debt issuance costs 77 37 224 37 Amortization of debt discount 1,546 736 4,487 736 Total $ 2,754 $ 1,357 $ 8,083 $ 1,357 Effective interest rate of the liability component 11 % 11 % 11 % 11 %

Restructuring (Tables)

Restructuring (Tables)	9 Months Ended
	Sep. 30, 2016
Restructuring Charges [Abstract]
Schedule of restructuring charges related to work-force reduction	Balance as of Expenses, Cash Balance as of 2016 workforce reduction $ 995 $ 33 $ (797 ) $ 231

The Company (Details)

The Company (Details) $ in Thousands	12 Months Ended
	Dec. 31, 2014state	Sep. 30, 2016USD ($)	Dec. 31, 2015USD ($)	Aug. 31, 2015
Long-term debt
Minimum age of ambulatory patient	5 years
Number of member states of the European Economic Area | state	31
Accumulated deficit | $		$ (708,313)	$ (592,998)
Convertible debt | 3.00% Convertible senior notes due 2022
Long-term debt
Interest rate				3.00%

Summary of significant accoun29

Summary of significant accounting policies (Details)	Jan. 01, 2016USD ($)	Dec. 31, 2014state	Sep. 30, 2016USD ($)	Dec. 31, 2015USD ($)
New Accounting Pronouncements or Change in Accounting Principle [Line Items]
Minimum age of ambulatory patient		5 years
Number of member states of the European Economic Area | state		31
Capitalized inventory			$ 1,300,000
Allowance for doubtful accounts receivable			400,000	$ 0
Accounting Standards Update 2015-03 | Deposits and other assets
New Accounting Pronouncements or Change in Accounting Principle [Line Items]
Debt issuance cost	$ (2,800,000)
Accounting Standards Update 2015-03 | Long-term debt.
New Accounting Pronouncements or Change in Accounting Principle [Line Items]
Debt issuance cost	$ 2,800,000
Unamortized debt issuance cost			$ 2,500,000
Minimum
New Accounting Pronouncements or Change in Accounting Principle [Line Items]
Gross profit margin (as a percent)			90.00%

Fair value of financial instr30

Fair value of financial instruments and marketable securities - Hierachy (Details) - USD ($) $ in Thousands	Sep. 30, 2016	Dec. 31, 2015
Financial assets and liabilities measured at fair value on recurring basis
Marketable securities	$ 198,052	$ 280,903
Recurring basis | Total
Financial assets and liabilities measured at fair value on recurring basis
Marketable securities	198,052	280,903
Warrant Liability	4	48
Stock appreciation rights liability	838	0
Recurring basis | Quoted prices in active markets for identical assets (level 1)
Financial assets and liabilities measured at fair value on recurring basis
Marketable securities	0	0
Warrant Liability	0	0
Stock appreciation rights liability	0	0
Recurring basis | Significant other observable inputs (level 2)
Financial assets and liabilities measured at fair value on recurring basis
Marketable securities	198,052	280,903
Warrant Liability	0	0
Stock appreciation rights liability	0	0
Recurring basis | Significant unobservable inputs (level 3)
Financial assets and liabilities measured at fair value on recurring basis
Marketable securities	0	0
Warrant Liability	4	48
Stock appreciation rights liability	$ 838	$ 0

Fair value of financial instr31

Fair value of financial instruments and marketable securities - Available for sale (Details) - USD ($)	Sep. 30, 2016	Dec. 31, 2015
Marketable securities accounted for as available-for-sale securities
Amortized Cost	$ 197,990,000	$ 281,492,000
Gross Unrealized Gains	171,000	83,000
Gross Unrealized Losses	(109,000)	(672,000)
Fair Value	198,052,000	280,903,000
Transfers of assets between Level 1 and Level 2 of the fair value measurement hierarchy	0	0
Commercial paper
Marketable securities accounted for as available-for-sale securities
Amortized Cost	17,935,000	26,877,000
Gross Unrealized Gains	53,000	80,000
Gross Unrealized Losses	0	0
Fair Value	17,988,000	26,957,000
Corporate debt securities
Marketable securities accounted for as available-for-sale securities
Amortized Cost	166,119,000	226,959,000
Gross Unrealized Gains	110,000	0
Gross Unrealized Losses	(109,000)	(640,000)
Fair Value	166,120,000	226,319,000
Government obligations
Marketable securities accounted for as available-for-sale securities
Amortized Cost	13,936,000	27,656,000
Gross Unrealized Gains	8,000	3,000
Gross Unrealized Losses	0	(32,000)
Fair Value	$ 13,944,000	$ 27,627,000

Fair value of financial instr32

Fair value of financial instruments and marketable securities - Balance Sheet (Details) - USD ($) $ in Thousands	Sep. 30, 2016	Dec. 31, 2015
Marketable securities on the balance sheet
Total Marketable securities, Less Than 12 Months	$ 163,941	$ 186,782
Total Marketable securities, More Than 12 Months	34,111	94,121
Commercial paper
Marketable securities on the balance sheet
Total Marketable securities, Less Than 12 Months	17,988	26,957
Total Marketable securities, More Than 12 Months	0	0
Corporate debt securities
Marketable securities on the balance sheet
Total Marketable securities, Less Than 12 Months	132,009	140,831
Total Marketable securities, More Than 12 Months	34,111	85,488
Government obligations
Marketable securities on the balance sheet
Total Marketable securities, Less Than 12 Months	13,944	18,994
Total Marketable securities, More Than 12 Months	$ 0	$ 8,633

Fair value of financial instr33

Fair value of financial instruments and marketable securities - Warrants and SARs (Details) - USD ($) $ / shares in Units, $ in Thousands	9 Months Ended	12 Months Ended
	Sep. 30, 2016	Dec. 31, 2015
SARs
Changes in the fair value of warrant liability and SARs liability
December 31, 2015	$ 0
Change in fair value	838
September 30, 2016	$ 838	$ 0
Minimum | SARs
Assumption used to estimate the fair value of warrant liability and SARs liability by utilizing the Black-Scholes option-pricing model
Volatility (as a percent)	69.00%
Risk-free interest rate (as a percent)	0.29%
Strike price (in dollars per share)	$ 6.76
Expected life	3 months 4 days
Maximum | SARs
Assumption used to estimate the fair value of warrant liability and SARs liability by utilizing the Black-Scholes option-pricing model
Volatility (as a percent)	75.00%
Risk-free interest rate (as a percent)	0.88%
Strike price (in dollars per share)	$ 30.86
Expected life	3 years 3 months 4 days
Common stock | SARs
Assumption used to estimate the fair value of warrant liability and SARs liability by utilizing the Black-Scholes option-pricing model
Fair value of shares (in dollars per share)	$ 14.01
Warrants
Changes in the fair value of warrant liability and SARs liability
December 31, 2015	$ 48
Change in fair value	(44)
September 30, 2016	$ 4	$ 48
Warrants | Minimum
Assumption used to estimate the fair value of warrant liability and SARs liability by utilizing the Black-Scholes option-pricing model
Volatility (as a percent)	68.00%	62.00%
Risk-free interest rate (as a percent)	0.52%	0.86%
Strike price (in dollars per share)	$ 128	$ 128
Expected life	8 months 16 days	1 year 6 months
Warrants | Maximum
Assumption used to estimate the fair value of warrant liability and SARs liability by utilizing the Black-Scholes option-pricing model
Volatility (as a percent)	75.00%	70.00%
Risk-free interest rate (as a percent)	0.88%	1.54%
Strike price (in dollars per share)	$ 2,520	$ 2,520
Expected life	2 years 11 months 23 days	3 years 8 months 12 days
Warrants | Common stock
Assumption used to estimate the fair value of warrant liability and SARs liability by utilizing the Black-Scholes option-pricing model
Fair value of shares (in dollars per share)	$ 14.01	$ 32.40

Other comprehensive income (l34

Other comprehensive income (loss) and accumulated other comprehensive items (Details) - USD ($) $ in Thousands	3 Months Ended	9 Months Ended
	Sep. 30, 2016	Sep. 30, 2016
AOCI Including Portion Attributable to Noncontrolling Interest, Net of Tax [Roll Forward]
Beginning Balance	$ 885	$ (1,200)
Other comprehensive (loss) income before reclassifications	(129)	1,956
Amounts reclassified from other comprehensive items	0	0
Other comprehensive (loss) income	(129)	1,956
Ending Balance	756	756
Unrealized Gains/(Losses) On Marketable Securities, net of tax
AOCI Including Portion Attributable to Noncontrolling Interest, Net of Tax [Roll Forward]
Beginning Balance	29	(589)
Other comprehensive (loss) income before reclassifications	(189)	429
Amounts reclassified from other comprehensive items	0	0
Other comprehensive (loss) income	(189)	429
Ending Balance	(160)	(160)
Foreign Currency Translation
AOCI Including Portion Attributable to Noncontrolling Interest, Net of Tax [Roll Forward]
Beginning Balance	856	(611)
Other comprehensive (loss) income before reclassifications	60	1,527
Amounts reclassified from other comprehensive items	0	0
Other comprehensive (loss) income	60	1,527
Ending Balance	$ 916	$ 916

Accounts payable and accrued 35

Accounts payable and accrued expenses (Details) - USD ($) $ in Thousands	Sep. 30, 2016	Dec. 31, 2015
Payables and Accruals [Abstract]
Employee compensation, benefits, and related accruals	$ 8,898	$ 11,187
Consulting and contracted research	13,336	13,753
Professional fees	1,679	2,523
Accounts payable	19,238	11,940
Accrued severance	231	0
Other	4,377	5,844
Accounts payable and accrued expenses	$ 47,759	$ 45,247

Warrants (Details)

Warrants (Details) - Warrants - Common stock - $ / shares	Sep. 30, 2016	Dec. 31, 2015
2,017
Warrants
Warrant shares (in shares)	6,250	6,250
Exercise price (in dollars per share)	$ 128	$ 128
2,019
Warrants
Warrant shares (in shares)	7,030	7,030
Exercise price (in dollars per share)	$ 128	$ 128
2,019
Warrants
Warrant shares (in shares)	130	130
Exercise price (in dollars per share)	$ 2,520	$ 2,520

Net loss per share - Numerator

Net loss per share - Numerator and Denominator (Details) - USD ($) $ / shares in Units, $ in Thousands	3 Months Ended		9 Months Ended
	Sep. 30, 2016	Sep. 30, 2015	Sep. 30, 2016	Sep. 30, 2015
Numerator
Net loss	$ (35,167)	$ (43,223)	$ (115,314)	$ (119,499)
Denominator
Denominator for basic and diluted net loss per share (in shares)	34,088,741	33,908,853	34,002,952	33,528,833
Net loss per share:
Basic and diluted (in dollars per share)	$ (1.03)	$ (1.27)	$ (3.39)	$ (3.56)

Net loss per share - Antidiluti

Net loss per share - Antidilutive (Details) - shares	9 Months Ended
	Sep. 30, 2016	Sep. 30, 2015
Net loss per share
Total shares excluded from calculation	6,104,745	5,141,399
Stock Options
Net loss per share
Total shares excluded from calculation	5,832,166	4,788,264
Unvested restricted stock awards and units
Net loss per share
Total shares excluded from calculation	272,579	353,135

Stock award plan - Share Base C

Stock award plan - Share Base Compensation (Details) - Stock option $ / shares in Units, $ in Thousands	9 Months Ended
	Sep. 30, 2016USD ($)$ / sharesshares
Number of options
Outstanding at the beginning of the period (in shares) | shares	4,826,477
Granted (in shares) | shares	1,440,445
Exercised (in shares) | shares	(85,325)
Forfeited/Cancelled (in shares) | shares	(349,431)
Outstanding at the end of the period (in shares) | shares	5,832,166
Vested or Expected to vest at the end of the period (in shares) | shares	3,032,483
Exercisable at the end of the period (in shares) | shares	2,613,982
Weighted-average exercise price
Outstanding at the beginning of the period (in dollars per share) | $ / shares	$ 37.20
Granted (in dollars per share) | $ / shares	28.55
Exercised (in dollars per share) | $ / shares	10.85
Forfeited/Cancelled (in dollars per share) | $ / shares	46.77
Outstanding at the end of the period (in dollars per share) | $ / shares	35.03
Vested or Expected to vest at the end of the period (in dollars per share) | $ / shares	35.79
Exercisable at the end of the period (in dollars per share) | $ / shares	$ 34.08
Weighted-average remaining contractual term
Outstanding at the end of the period	8 years 4 days
Vested or Expected to vest at the end of the period	8 years 6 months
Exercisable at the end of the period	7 years 4 months 17 days
Aggregate intrinsic value
Outstanding at the end of the period (in dollars) | $	$ 4,132
Vested or Expected to vest at the end of the period (in dollars) | $	1,200
Exercisable at the end of the period (in dollars) | $	$ 2,867
Minimum
Valuation assumptions
Risk-free interest rate (as a percent)	1.30%
Expected volatility (as a percent)	67.00%
Expected term	5 years 18 days
Maximum
Valuation assumptions
Risk-free interest rate (as a percent)	2.24%
Expected volatility (as a percent)	78.00%
Expected term	10 years

Stock award plan - Restricted S

Stock award plan - Restricted Stock (Details) - USD ($) $ / shares in Units, $ in Thousands	1 Months Ended	3 Months Ended		9 Months Ended
	May 31, 2016	Sep. 30, 2016	Sep. 30, 2015	Sep. 30, 2016	Sep. 30, 2015
Weighted Average Grant Date Fair Value
Share-based compensation expense		$ 8,959	$ 8,054	$ 26,610	$ 26,130
Research and development
Weighted Average Grant Date Fair Value
Share-based compensation expense		4,319	3,828	12,734	12,452
Selling, general and administrative
Weighted Average Grant Date Fair Value
Share-based compensation expense		$ 4,640	$ 4,226	$ 13,876	$ 13,678
Unvested restricted stock
Number of Shares
Balance at the beginning of the period (in shares)				344,335
Granted (in shares)				141,185
Vested (in shares)				(163,635)
Forfeited (in shares)				(49,306)
Balance at the end of the period (in shares)		272,579		272,579
Weighted Average Grant Date Fair Value
Balance at the beginning of the period (in dollars per share)				$ 10.85
Granted (in dollars per share)				30.86
Vested (in dollars per share)				10.85
Forfeited (in dollars per share)				18.69
Balance at the end of the period (in dollars per share)		$ 19.80		$ 19.80
SARs
Number of Shares
Granted (in shares)	897,290
Weighted Average Grant Date Fair Value
Share-based compensation expense				$ 800

Stock award plan Stock award pl

Stock award plan Stock award plan- Narrative (Details) - USD ($) $ / shares in Units, $ in Thousands	Mar. 05, 2013	Jun. 30, 2016	May 31, 2016	May 31, 2013	Sep. 30, 2016	Sep. 30, 2015	Sep. 30, 2016	Sep. 30, 2015
Stock option plan
Share-based compensation expense					$ 8,959	$ 8,054	$ 26,610	$ 26,130
Unrecognized compensation cost					$ 70,800		$ 70,800
Weighted average remaining service period for recognition of unrecognized compensation cost							2 years 3 months 26 days
Common stock
Stock option plan
Number of shares available for issuance (in shares)					345,719		345,719
Unvested restricted stock
Stock option plan
Granted (in shares)							141,185
Stock option
Stock option plan
Granted (in shares)							1,440,445
Inducement grants for non-statutory stock options (in shares)							116,000
Expected dividend yield (as a percent)							0.00%
Weighted average grant date fair value (in dollars per share)							$ 17.67
SARs
Stock option plan
Granted (in shares)			897,290
Vesting period							4 years
Share-based compensation expense							$ 800
2013 Stock Incentive Plan
Stock option plan
Number of shares available for issuance (in shares)	0
2013 Stock Incentive Plan | Common stock
Stock option plan
Number of shares authorized (in shares)	739,937
2013 Stock Incentive Plan | Unvested restricted stock
Stock option plan
Grants in Period (in shares)	735,324
2013 Stock Incentive Plan | Stock option
Stock option plan
Granted (in shares)	4,613
2009 Equity and Long Term Incentive Plan
Stock option plan
Number of additional shares authorized (in shares)				2,500,000
2009 Equity and Long Term Incentive Plan and 2013 Stock Incentive Plan | Common stock
Stock option plan
Number of shares available for issuance (in shares)				122,296
2009 Equity and Long Term Incentive Plan and 2013 Stock Incentive Plan | 1998 Employee, Director and Consultant Stock Option Plan | Common stock | Maximum
Stock option plan
Number of shares subject to outstanding awards (in shares)				3,040,444
2013 Long Term Incentive Plan | Minimum
Stock option plan
Annual increase in the number of shares (in shares) on the first day of the fiscal year				2,500,000
Annual increase in the number of shares outstanding on the first day of the fiscal year (as a percent)				4.00%
Employee Stock Purchase Plan
Stock option plan
Number of shares authorized (in shares)		1,000,000
Award requisite service period		6 months
Share-based compensation expense							$ 100
Purchase price of common stock, percent		85.00%
Employee stock purchase plan, voting percentage limit		5.00%

Convertible Senior Notes (Detai

Convertible Senior Notes (Details) - 3.00% Convertible senior notes due 2022 - Convertible debt - USD ($)	Sep. 30, 2016	Dec. 31, 2015	Aug. 31, 2015
Long-term debt
Principal	$ 150,000,000	$ 150,000,000	$ 150,000,000
Less: Debt issuance costs	(2,536,000)	(2,760,000)
Less: Debt discount, net	(50,905,000)	(55,392,000)
Net carrying amount	$ 96,559,000	$ 91,848,000

Convertible Senior Notes - Inte

Convertible Senior Notes - Interest Expense (Details) - USD ($) $ in Thousands	3 Months Ended		9 Months Ended
	Sep. 30, 2016	Sep. 30, 2015	Sep. 30, 2016	Sep. 30, 2015
Long-term debt
Amortization of debt issuance costs			$ 224	$ 37
Convertible debt | 3.00% Convertible senior notes due 2022
Long-term debt
Contractual interest expense	$ 1,131	$ 584	3,372	584
Amortization of debt issuance costs	77	37	224	37
Amortization of debt discount	1,546	736	4,487	736
Total	$ 2,754	$ 1,357	$ 8,083	$ 1,357
Effective interest rate of the liability component	11.00%	11.00%	11.00%	11.00%

Convertible Senior Notes - Narr

Convertible Senior Notes - Narrative (Details) - Convertible debt - 3.00% Convertible senior notes due 2022	1 Months Ended	9 Months Ended
	Aug. 31, 2015USD ($)item$ / shares	Sep. 30, 2016USD ($)	Dec. 31, 2015USD ($)
Long-term debt
Debt principal amount	$ 150,000,000	$ 150,000,000	$ 150,000,000
Interest rate	3.00%
Net proceeds from issuance of convertible notes	$ 145,400,000
Trading days, number | item	20
Consecutive trading days, period	30 days
Stock price trigger (as a percent)	130.00%
Business days, period	5 days
Consecutive trading-day period	5 days
Common stock per principal amount	$ 1,000
Maximum product of the closing sale price of shares of the Company's common stock and the applicable conversion rate for such trading day (as a percent)	98.00%
Conversion ratio	17.7487
Conversion price per share | $ / shares	$ 56.34
Convertible instruments principal and unpaid interest payable upon events of default	100.00%
Minimum percentage of principal held by convertible debt instrument holders required to issue notice for declaration of principal and unpaid interest payable upon events of default (as a percent)	25.00%
Term of the convertible notes	7 years
Net deferred tax liability in connection with convertible notes	$ 22,300,000
Fair value of convertible notes		$ 89,200,000
Remaining contractual life of the convertible notes		5 years 10 months 24 days
Redemption on or after August 20, 2018
Long-term debt
Trading days, number | item	19
Consecutive trading days, period	30 days
Stock price trigger (as a percent)	130.00%
Redemption price (as a percent)	100.00%
Sinking fund	$ 0

Restructuring (Details)

Restructuring (Details) $ in Thousands	3 Months Ended
	Sep. 30, 2016USD ($)
Research and development and selling, general and administrative expenses
Restructuring Cost and Reserve [Line Items]
Work-force reduction charges	$ 2,500
2016 Workforce Reduction
Restructuring Reserve [Roll Forward]
Restructuring Reserve, Beginning Balance	995
Expenses, net	33
Cash	(797)
Restructuring Reserve, Ending Balance	$ 231

Commitments and contingencies (

Commitments and contingencies (Details) - Funding agreement - Wellcome trust $ in Millions	Sep. 30, 2016USD ($)
Other Commitments [Abstract]
Development and regulatory milestone payments which the entity may be obligated to pay	$ 0.8
Maximum
Other Commitments [Abstract]
Development and regulatory milestone payments which the entity may be obligated to pay	$ 68.9