Ionis Pharmaceuticals (IONS) 10-Q 3 May 23 2023 Q1 Quarterly report Financial data

Document and Entity Information

Document and Entity Information - shares	3 Months Ended
	Mar. 31, 2023	Apr. 27, 2023
Cover [Abstract]
Document Type	10-Q
Amendment Flag	false
Document Quarterly Report	true
Document Period End Date	Mar. 31, 2023
Current Fiscal Year End Date	--12-31
Document Fiscal Year Focus	2023
Document Fiscal Period Focus	Q1
Document Transition Report	false
Entity File Number	000-19125
Entity Registrant Name	Ionis Pharmaceuticals, Inc.
Entity Central Index Key	0000874015
Entity Incorporation, State or Country Code	DE
Entity Tax Identification Number	33-0336973
Entity Address, Address Line One	2855 Gazelle Court
Entity Address, City or Town	Carlsbad
Entity Address, State or Province	CA
Entity Address, Postal Zip Code	92010
City Area Code	760
Local Phone Number	931-9200
Title of 12(b) Security	Common Stock, $.001 Par Value
Trading Symbol	IONS
Security Exchange Name	NASDAQ
Entity Current Reporting Status	Yes
Entity Interactive Data Current	Yes
Entity Filer Category	Large Accelerated Filer
Entity Small Business	false
Entity Emerging Growth Company	false
Entity Shell Company	false
Entity Common Stock, Shares Outstanding		143,092,117

CONDENSED CONSOLIDATED BALANCE

CONDENSED CONSOLIDATED BALANCE SHEETS - USD ($) $ in Thousands	Mar. 31, 2023	Dec. 31, 2022
Current assets:
Cash and cash equivalents	$ 309,031	$ 276,472
Short-term investments	2,037,750	1,710,397
Contracts receivable	13,914	25,538
Inventories	22,200	22,033
Other current assets	159,724	168,254
Total current assets	2,542,619	2,202,694
Property, plant and equipment, net	85,158	74,294
Right-of-use assets	179,148	181,544
Deposits and other assets	78,296	75,344
Total assets	2,885,221	2,533,876
Current liabilities:
Accounts payable	10,499	17,921
Accrued compensation	18,160	49,178
Accrued liabilities	112,702	140,101
Income taxes payable	17,286	6,249
Current portion of deferred contract revenue	92,335	90,577
Other current liabilities	8,239	7,535
Total current liabilities	259,221	311,561
Long-term deferred contract revenue	272,973	287,768
Liability related to sale of future royalties, net	505,081	0
Long-term lease liabilities	177,000	178,941
Long-term mortgage debt	8,811	8,847
Long-term obligations	7,487	7,126
Total liabilities	2,398,651	1,960,989
Stockholders' equity:
Common stock, $0.001 par value; 300,000,000 shares authorized, 143,022,539 and 142,057,736 shares issued and outstanding at March 31, 2023 (unaudited) and December 31, 2022, respectively	143	142
Additional paid-in capital	2,089,358	2,059,850
Accumulated other comprehensive loss	(48,983)	(57,480)
Accumulated deficit	(1,553,948)	(1,429,625)
Total stockholders' equity	486,570	572,887
Total liabilities and stockholders' equity	2,885,221	2,533,876
0 Percent Convertible Senior Notes [Member]
Current liabilities:
Convertible senior notes, net	623,025	622,242
0.125 Percent Convertible Senior Notes [Member]
Current liabilities:
Convertible senior notes, net	$ 545,053	$ 544,504

CONDENSED CONSOLIDATED BALANC_2

CONDENSED CONSOLIDATED BALANCE SHEETS (Parenthetical) - $ / shares	Mar. 31, 2023	Dec. 31, 2022
Stockholders' equity:
Common stock, par value (in dollars per share)	$ 0.001	$ 0.001
Common stock, shares authorized (in shares)	300,000,000	300,000,000
Common stock, shares issued (in shares)	143,022,539	142,057,736
Common stock, shares outstanding (in shares)	143,022,539	142,057,736
0 Percent Convertible Senior Notes [Member]
LIABILITIES AND STOCKHOLDERS' EQUITY
Interest rate on convertible senior notes	0%	0%
0.125 Percent Convertible Senior Notes [Member]
LIABILITIES AND STOCKHOLDERS' EQUITY
Interest rate on convertible senior notes	0.125%	0.125%

CONDENSED CONSOLIDATED STATEMEN

CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS - USD ($) shares in Thousands, $ in Thousands	3 Months Ended
	Mar. 31, 2023	Mar. 31, 2022
Revenue:
Revenue	$ 130,524	$ 141,919
Expenses:
Cost of sales	1,343	4,170
Research, development and patent	197,813	161,126
Selling, general and administrative	45,516	34,127
Total operating expenses	244,672	199,423
Loss from operations	(114,148)	(57,504)
Other income (expense):
Investment income	18,627	1,993
Interest expense	(1,608)	(2,122)
Interest expense related to sale of future royalties	(15,515)	0
Loss on investments	(529)	(6,625)
Other income	230	187
Loss before income tax expense	(112,943)	(64,071)
Income tax expense	(11,380)	(1,094)
Net loss	$ (124,323)	$ (65,165)
Basic net loss per share (in dollars per share)	$ (0.87)	$ (0.46)
Diluted net loss per share (in dollars per share)	$ (0.87)	$ (0.46)
Shares used in computing basic net loss per share (in shares)	142,735	141,599
Shares used in computing diluted net loss per share (in shares)	142,735	141,599
Commercial Revenue [Member]
Revenue:
Revenue	$ 67,768	$ 72,285
SPINRAZA Royalties [Member]
Revenue:
Revenue	50,247	53,818
TEGSEDI and WAYLIVRA Revenue, Net [Member]
Revenue:
Revenue	6,478	6,160
Licensing and Other Royalty Revenue [Member]
Revenue:
Revenue	11,043	12,307
Research and Development Revenue [Member]
Revenue:
Revenue	62,756	69,634
Collaborative Agreement Revenue [Member]
Revenue:
Revenue	38,334	49,784
Eplontersen Joint Development Revenue [Member]
Revenue:
Revenue	$ 24,422	$ 19,850

CONDENSED CONSOLIDATED STATEM_2

CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS - USD ($) $ in Thousands	3 Months Ended
	Mar. 31, 2023	Mar. 31, 2022
CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS [Abstract]
Net loss	$ (124,323)	$ (65,165)
Unrealized gains (losses) on debt securities, net of tax	8,393	(15,756)
Currency translation adjustment	104	(154)
Comprehensive loss	$ (115,826)	$ (81,075)

CONDENSED CONSOLIDATED STATEM_3

CONDENSED CONSOLIDATED STATEMENTS OF STOCKHOLDERS' EQUITY - USD ($) shares in Thousands, $ in Thousands	Common Stock [Member]	Additional Paid in Capital [Member]	Accumulated Other Comprehensive Loss [Member]	Accumulated Deficit [Member]	Total
Balance at Dec. 31, 2021	$ 141	$ 1,964,167	$ (32,668)	$ (1,159,903)	$ 771,737
Balance (in shares) at Dec. 31, 2021	141,210
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Net loss	$ 0	0	0	(65,165)	(65,165)
Change in unrealized gains (losses), net of tax	0	0	(15,756)	0	(15,756)
Foreign currency translation	0	0	(154)	0	(154)
Issuance of common stock in connection with employee stock plans	$ 1	1,848	0	0	1,849
Issuance of common stock in connection with employee stock plans (in shares)	847
Stock-based compensation expense	$ 0	26,236	0	0	26,236
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options	$ 0	(9,173)	0	0	(9,173)
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options (in shares)	(304)
Balance at Mar. 31, 2022	$ 142	1,983,078	(48,578)	(1,225,068)	709,574
Balance (in shares) at Mar. 31, 2022	141,753
Balance at Dec. 31, 2022	$ 142	2,059,850	(57,480)	(1,429,625)	572,887
Balance (in shares) at Dec. 31, 2022	142,058
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Net loss	$ 0	0	0	(124,323)	(124,323)
Change in unrealized gains (losses), net of tax	0	0	8,393	0	8,393
Foreign currency translation	0	0	104	0	104
Issuance of common stock in connection with employee stock plans	$ 1	2,560	0	0	2,561
Issuance of common stock in connection with employee stock plans (in shares)	965
Stock-based compensation expense	$ 0	26,948	0	0	26,948
Balance at Mar. 31, 2023	$ 143	$ 2,089,358	$ (48,983)	$ (1,553,948)	$ 486,570
Balance (in shares) at Mar. 31, 2023	143,023

CONDENSED CONSOLIDATED STATEM_4

CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS - USD ($) $ in Thousands	3 Months Ended
	Mar. 31, 2023	Mar. 31, 2022
Operating activities:
Net loss	$ (124,323)	$ (65,165)
Adjustments to reconcile net loss to net cash used in operating activities:
Depreciation	2,604	3,701
Amortization of right-of-use operating lease assets	2,395	602
Amortization of other assets	607	592
Amortization of premium (discount) on investments, net	(5,042)	4,175
Amortization of debt issuance costs	1,486	1,343
Non-cash interest related to sale of future royalties	15,363	0
Stock-based compensation expense	26,948	26,236
Loss (gain) on investments	529	(10)
Non-cash losses related to disposal of property, plant and equipment	0	527
Non-cash losses related to other assets	445	110
Changes in operating assets and liabilities:
Contracts receivable	11,624	35,774
Inventories	(167)	774
Other current and long-term assets	5,312	(7,222)
Income taxes payable	11,037	865
Accounts payable	(10,295)	2,878
Accrued compensation	(31,018)	(22,285)
Accrued liabilities and other current liabilities	(28,460)	10,473
Deferred contract revenue	(13,037)	(25,018)
Net cash used in operating activities	(133,992)	(31,650)
Investing activities:
Purchases of short-term investments	(688,278)	(462,855)
Proceeds from sale of short-term investments	374,363	178,837
Purchases of property, plant and equipment	(10,472)	(2,705)
Acquisition of licenses and other assets, net	(1,253)	(826)
Net cash used in investing activities	(325,640)	(287,549)
Financing activities:
Proceeds from equity, net	2,560	1,848
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options	0	(9,173)
Proceeds from sale of future royalties	500,000	0
Payments of transaction costs related to sale of future royalties	(10,434)	0
Principal payments on mortgage debt	(39)	0
Net cash provided by (used in) financing activities	492,087	(7,325)
Effects of exchange rates on cash	104	(154)
Net increase (decrease) in cash and cash equivalents	32,559	(326,678)
Cash and cash equivalents at beginning of period	276,472	869,191
Cash and cash equivalents at end of period	309,031	542,513
Supplemental disclosures of cash flow information:
Interest paid	89	594
Income taxes paid	293	2
Supplemental disclosures of non-cash investing and financing activities:
Amounts accrued for capital and patent expenditures	$ 3,058	$ 1,344

Organization and Basis of Prese

Organization and Basis of Presentation	3 Months Ended
	Mar. 31, 2023
Organization and Basis of Presentation [Abstract]
Organization and Basis of Presentation	1. Organization and Basis of Presentation Organization and Business Activity We incorporated in California on January 10, 1989. In conjunction with our initial public offering, we reorganized as a Delaware corporation in April 1991. We are a leader in the discovery and development of RNA-targeted therapeutics. Basis of Presentation We prepared the unaudited interim condensed consolidated financial statements for the three months ended March 31, 2023 and 2022 on the same basis as the audited financial statements for the year ended December 31, 2022. We included all normal recurring adjustments in the financial statements, which we considered necessary for a fair presentation of our financial position at such dates and our operating results and cash flows for those periods. Our operating results for the interim periods may not be indicative of what our operating results will be for the entire year. For more complete financial information, these financial statements, and notes thereto, should be read in conjunction with the audited financial statements for the year ended December 31, 2022 included in our Annual Report on Form 10-K filed with the Securities and Exchange Commission, or SEC. In our condensed consolidated financial statements, we included the accounts of Ionis Pharmaceuticals, Inc. and the consolidated results of our wholly owned subsidiary, Akcea Therapeutics, Inc. and its wholly owned subsidiaries (“we”, “us” or “our”). We operate as a single single Use of Estimates We prepare our condensed consolidated financial statements in conformity with accounting principles generally accepted in the United States, or

Significant Accounting Policies

Significant Accounting Policies	3 Months Ended
	Mar. 31, 2023
Significant Accounting Policies [Abstract]
Significant Accounting Policies	2. Significant Accounting Policies Our significant accounting policies have not changed substantially from those included in our Annual Report on Form 10-K for the year ended December 31, 2022, other than as discussed below. Liability Related to Sale of Future Royalties In January 2023, we entered into a royalty purchase agreement with Royalty Pharma Investments, or Royalty Pharma, to monetize a portion of our future SPINRAZA and pelacarsen royalties we are entitled to under our arrangements with Biogen and Novartis, respectively. Refer to Note 10, Liability Related to Sale of Future Royalties We record upfront payments and milestone payments we receive from the sale of future royalties as a liability, net of transaction costs. We record royalty payments made to Royalty Pharma as a reduction of the liability and amortize the transaction costs over the estimated life of the related royalty stream. We account for the associated interest expense under the effective interest rate method, while continuing to recognize the full amount of royalty revenue in the period in which the counterparty sells the related product and recognizes the related revenue. The liability related to the sale of future royalties, effective interest rate and the related interest expense are calculated using our current estimate of anticipated future royalty payments under the arrangement, which we periodically reassess based on internal projections and information from our partners who are responsible for commercializing the medicines. If there is a material change in our estimate, we will prospectively adjust the liability related to the sale of future royalties, effective interest rate and the related interest expense. Recently Adopted Accounting Standards We do not expect any recently issued accounting standards to have a material impact to our financial results.

Supplemental Financial Data

Supplemental Financial Data	3 Months Ended
	Mar. 31, 2023
Supplemental Financial Data [Abstract]
Supplemental Financial Data [Text Block]	3. Supplemental Financial Data Inventories Our inventory consisted of the following (in thousands): March 31, 2023 December 31, 2022 Raw materials: Raw materials - clinical $ 17,356 $ 17,061 Raw materials - commercial 2,786 2,699 Total raw materials 20,142 19,760 Work in process 1,840 2,109 Finished goods 218 164 Total inventory $ 22,200 $ 22,033 Accrued Liabilities Our accrued liabilities consisted of the following (in thousands): March 31, 2023 December 31, 2022 Clinical development expenses $ 85,694 $ 116,460 In-licensing expenses 12,704 7,945 Commercial expenses 4,704 3,498 Other miscellaneous expenses 9,600 12,198 Total accrued liabilities $ 112,702 $ 140,101

Collaborative Arrangements and

Collaborative Arrangements and Licensing Agreements	3 Months Ended
	Mar. 31, 2023
Collaborative Arrangements and Licensing Agreements [Abstract]
Collaborative Arrangements and Licensing Agreements	4. Collaborative Arrangements and Licensing Agreements Below, we have included our Biogen and GSK collaborations, which are our only collaborations with substantive changes during 2023 from those included in Part IV, Item 15, Note 7 of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2022. Biogen We have several strategic collaborations with Biogen focused on using antisense technology to advance the treatment of neurological disorders. We developed and licensed to Biogen SPINRAZA, our approved medicine to treat people with spinal muscular atrophy, or SMA. Under our 2013 strategic neurology collaboration, Biogen developed QALSODY (tofersen), our recently approved medicine to treat people with superoxide dismutase 1 amyotrophic lateral sclerosis, or SOD1-ALS. We and Biogen are currently developing numerous investigational medicines to treat neurodegenerative diseases under these collaborations, including medicines in development to treat people with , SMA, Angelman Syndrome, Alzheimer’s disease and Parkinson’s disease. In addition to these medicines, our collaborations with Biogen include a substantial research pipeline that addresses a broad range of neurological diseases. From inception through , we have received more than $ billion in payments from our Biogen collaborations. In the first quarter of 2023, we earned a $10 million milestone payment from Biogen when we advanced ION582 under our 2012 neurology collaboration. We will recognize revenue as we perform services based on our effort to satisfy our research and development, or R&D, services performance obligation relative to the total effort expected to satisfy our performance obligation for ION582. We will achieve the next payment of up to $25 million if Biogen advances another medicine under our 2012 neurology collaboration. During the three months ended March 31, 2023 and 2022, we earned the following revenue from our relationship with Biogen (in thousands, except percentage amounts): Three Months Ended March 31, 2023 2022 SPINRAZA royalties (commercial revenue) $ 50,247 $ 53,818 R&D revenue 20,254 40,049 Total revenue from our relationship with Biogen $ 70,501 $ 93,867 Percentage of total revenue 54 % 66 % In April 2023, we earned a $16 million milestone payment from Biogen when the FDA approved Biogen’s New Drug Application, or NDA, for QALSODY. We will achieve the next payment of up to $20 million if Biogen advances a medicine under the 2013 strategic neurology collaboration. Our condensed consolidated balance sheets at March 31, 2023 and December 31, 2022 GSK In March 2010, we entered into a collaboration with GSK using our antisense drug discovery platform to discover and develop new medicines against targets for serious and rare diseases, including infectious diseases and some conditions causing blindness. Our collaboration with GSK currently includes bepirovirsen, our medicine in development targeting hepatitis B virus, or HBV. We designed this medicine to reduce the production of viral proteins associated with HBV infection. In the third quarter of 2019, following positive Phase 2 results, GSK licensed our HBV program. GSK is responsible for all global development, regulatory and commercialization activities and costs for the HBV program In the first quarter of 2023, we earned a $15 million milestone payment when GSK initiated a Phase 3 program of bepirovirsen. We recognized this milestone payment as R&D revenue in full in the first quarter of 2023 because we did not have any remaining performance obligations related to the milestone payment. We will achieve the next payment of $15 million if the FDA accepts an NDA filing of bepirovirsen for review. During the three months ended March 31, 2023 and 2022, we earned the following revenue from our relationship with GSK (in thousands, except percentage amounts): Three Months Ended March 31, 2023 2022 R&D revenue $ 15,000 $ — Percentage of total revenue 11 % — We did not have any deferred revenue from our relationship with GSK at March 31, 2023 or December 31, 2022.

Basic and Diluted Net Loss Per

Basic and Diluted Net Loss Per Share	3 Months Ended
	Mar. 31, 2023
Basic and Diluted Net Loss Per Share [Abstract]
Basic and Diluted Net Loss Per Share	5. Basic and Diluted Net Loss Per Share Basic net loss per share We calculated our basic net loss per share for the three months ended March 31, 2023 and 2022 by dividing our net loss by our weighted-average number of common shares outstanding during the period. Diluted net loss per share For the three months ended March 31, 2023 and 2022, we incurred a net loss; therefore, we did not include dilutive common equivalent shares in the computation of diluted net loss per share because the effect would have been anti-dilutive. Common stock from the following would have had an anti-dilutive effect on net loss per share: ● 0 percent convertible senior notes, or 0% Notes; ● Note hedges related to the 0% Notes; ● 0.125 percent convertible senior notes, or 0.125% Notes; ● Note hedges related to the 0.125% Notes; ● Dilutive stock options; ● Unvested restricted stock units, or RSUs; ● Unvested performance restricted stock units, or PRSUs; and ● Employee Stock Purchase Plan, or ESPP. Additionally as of March 31, 2023, we had warrants related to our 0% and 0.125% Notes outstanding. We will include the shares issuable under these warrants in our calculation of diluted earnings per share when the average market price per share of our common stock for the reporting period exceeds the strike price of the warrants.

Investments

Investments	3 Months Ended
	Mar. 31, 2023
Investments [Abstract]
Investments	6. Investments The following table summarizes the contract maturity of the available-for-sale securities we held as of March 31, 2023: One year 74 % After one year two years 23 % After two years three and a half years 3 % Total 100 % As illustrated above, at March 31, 2023, 97 percent of our available-for-sale securities had a maturity of less than two years. All of our available-for-sale debt securities are available to us for use in our current operations. As a result, we categorize all of these securities as current assets even though the stated maturity of some individual securities may be one year or more beyond the balance sheet date. We invest in available-for-sale securities At March 31, 2023, we had an equity ownership interest of less than 20 percent in seven private companies and three public companies with which we conduct business. The following is a summary of our investments (in thousands): Amortized Gross Unrealized Estimated March 31, 2023 Cost Gains Losses Fair Value Available-for-sale debt securities: Corporate debt securities (1) $ 623,940 $ 62 $ (6,026 ) $ 617,976 Debt securities issued by U.S. government agencies 247,629 69 (1,283 ) 246,415 Debt securities issued by the U.S. Treasury (1) 556,394 62 (3,738 ) 552,718 Debt securities issued by states of the U.S. and political subdivisions of the states 57,322 4 (498 ) 56,828 Total debt securities with a maturity of one year or less 1,485,285 197 (11,545 ) 1,473,937 Corporate debt securities 200,661 336 (5,205 ) 195,792 Debt securities issued by U.S. government agencies 99,635 256 (649 ) 99,242 Debt securities issued by the U.S. Treasury 257,651 364 (2,726 ) 255,289 Debt securities issued by states of the U.S. and political subdivisions of the states 14,564 106 (182 ) 14,488 Total debt securities with a maturity of more than one year 572,511 1,062 (8,762 ) 564,811 Total available-for-sale debt securities $ 2,057,796 $ 1,259 $ (20,307 ) $ 2,038,748 Equity securities: Publicly traded equity securities included in other current assets (2) $ 11,897 $ — $ (4,508 ) $ 7,389 Privately held equity securities included in deposits and other assets (3) 23,115 25,001 (5,125 ) 42,991 Total equity securities 35,012 25,001 (9,633 ) 50,380 Total available-for-sale debt and equity securities $ 2,092,808 $ 26,260 $ (29,940 ) $ 2,089,128 Amortized Gross Unrealized Estimated December 31, 2022 Cost Gains Losses Fair Value Available-for-sale debt securities: Corporate debt securities (1) $ 513,790 $ 23 $ (4,365 ) $ 509,448 Debt securities issued by U.S. government agencies 133,585 — (1,829 ) 131,756 Debt securities issued by the U.S. Treasury (1) 512,655 23 (5,124 ) 507,554 Debt securities issued by states of the U.S. and political subdivisions of the states 57,484 18 (686 ) 56,816 Other municipal debt securities 6,008 — (14 ) 5,994 Total debt securities with a maturity of one year or less 1,223,522 64 (12,018 ) 1,211,568 Corporate debt securities 227,631 14 (10,143 ) 217,502 Debt securities issued by U.S. government agencies 34,339 — (1,040 ) 33,299 Debt securities issued by the U.S. Treasury 245,030 — (4,109 ) 240,921 Debt securities issued by states of the U.S. and political subdivisions of the states 18,314 116 (329 ) 18,101 Total debt securities with a maturity of more than one year 525,314 130 (15,621 ) 509,823 Total available-for-sale debt securities $ 1,748,836 $ 194 $ (27,639 ) $ 1,721,391 Equity securities: Publicly traded equity securities included in other current assets (2) $ 11,897 $ — $ (1,358 ) $ 10,539 Privately held equity securities included in deposits and other assets (3) 23,115 17,257 — 40,372 Total equity securities 35,012 17,257 (1,358 ) 50,911 Total available-for-sale debt and equity securities $ 1,783,848 $ 17,451 $ (28,997 ) $ 1,772,302 (1) Includes investments classified as cash equivalents in our condensed consolidated balance sheets. (2) Our publicly traded equity securities are included in other current assets. We recognize publicly traded equity securities at fair value. In the three months ended March 31, 2023, we recognized a $3.2 million unrealized loss in our condensed consolidated statements of operations related to a decrease in the fair value of our investments in publicly traded companies. (3) Our privately held equity securities are included in deposits and other assets. We recognize our privately held equity securities at . In the three months ended March 31, 2023, we recorded a net gain of $ million in our condensed consolidated statements of operations related to changes in the fair value of our investments in privately held companies. The following is a summary of our investments we consider to be temporarily impaired at March 31, 2023 (in thousands, except for number of investments): Less than 12 Months of Temporary Impairment More than 12 Months of Temporary Impairment Total Temporary Impairment Number of Investments Estimated Fair Value Unrealized Losses Estimated Fair Value Unrealized Losses Estimated Fair Value Unrealized Losses Corporate debt securities 361 $ 434,500 $ (1,697 ) $ 291,713 $ (9,534 ) $ 726,213 $ (11,231 ) Debt securities issued by U.S. government agencies 68 138,211 (424 ) 70,965 (1,508 ) 209,176 (1,932 ) Debt securities issued by the U.S. Treasury 64 603,444 (3,873 ) 91,448 (2,591 ) 694,892 (6,464 ) Debt securities issued by states of the U.S. and political subdivisions of the states 110 22,778 (140 ) 32,792 (540 ) 55,570 (680 ) Total temporarily impaired securities 603 $ 1,198,933 $ (6,134 ) $ 486,918 $ (14,173 ) $ 1,685,851 $ (20,307 ) We believe that the decline in value of these securities is temporary and is primarily related to the change in market interest rates since purchase rather than underlying credit deterioration for any of the issuers. We believe it is more likely than not that we will be able to hold our debt securities with declines in value to maturity. Therefore, we anticipate full recovery of our debt securities’ amortized cost basis at maturity.

Fair Value Measurements

Fair Value Measurements	3 Months Ended
	Mar. 31, 2023
Fair Value Measurements [Abstract]
Fair Value Measurements	7. Fair Value Measurements The following tables present the major security types we held at March 31, 2023 and December 31, 2022 that we regularly measure and carry at fair value. The following tables segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective security’s fair value (in thousands): At March 31, 2023 Quoted Prices in Active Markets (Level 1) Significant Other Observable Inputs (Level 2) Cash equivalents (1) $ 276,352 $ 276,352 $ — Corporate debt securities (2) 813,768 — 813,768 Debt securities issued by U.S. government agencies (2) 345,657 — 345,657 Debt securities issued by the U.S. Treasury (2) 808,007 808,007 — Debt securities issued by states of the U.S. and political subdivisions of the states (3) 71,316 — 71,316 Publicly traded equity securities included in other current assets (4) 7,389 7,389 — Total $ 2,322,489 $ 1,091,748 $ 1,230,741 At December 31, 2022 Quoted Prices in Active Markets (Level 1) Significant Other Observable Inputs (Level 2) Cash equivalents (1) $ 211,655 $ 211,655 $ — Corporate debt securities (5) 726,950 — 726,950 Debt securities issued by U.S. government agencies (2) 165,055 — 165,055 Debt securities issued by the U.S. Treasury (2) 748,475 748,475 — Debt securities issued by states of the U.S. and political subdivisions of the states (2) 74,917 — 74,917 Other municipal debt securities (2) 5,994 — 5,994 Publicly traded equity securities included in other current assets (4) 10,539 10,539 — Total $ 1,943,585 $ 970,669 $ 972,916 The following footnotes reference lines in our condensed consolidated balance sheets: (1) Included in cash and cash equivalents in our condensed consolidated balance sheets. (2) Included in short-term investments in our condensed consolidated balance sheets. (3) $1.0 million was included in cash and cash equivalents in our condensed consolidated balance sheets, with the difference included in short-term investments in our condensed consolidated balance sheets. (4) Included in other current assets in our condensed consolidated balance sheets. (5) $11.0 million was included in cash and cash equivalents in our condensed consolidated balance sheets, with the difference included in short-term investments in our condensed consolidated balance sheets. Convertible Notes Our 0.125% Notes and 0% Notes had a fair value of $506.3 million and $578.4 million at March 31, 2023, respectively. Our 0.125% Notes and 0% Notes had a fair value of $498.9 million and $587.3 million at December 31, 2022, respectively. We determine the fair value of our notes based on quoted market prices for these notes, which are Level 2 measurements because the notes do not trade regularly.

Stock-based Compensation Expens

Stock-based Compensation Expense	3 Months Ended
	Mar. 31, 2023
Stock-based Compensation Expense [Abstract]
Stock-based Compensation Expense	8. Stock-based Compensation Expense We measure stock-based compensation expense for equity-classified awards, principally related to stock options, RSUs, PRSUs and stock purchase rights under our ESPP based on the estimated fair value of the award on the date of grant. We recognize the value of the portion of the award that we ultimately expect to vest as stock-based compensation expense over the requisite service period in our condensed consolidated statements of operations. We reduce stock-based compensation expense for estimated forfeitures at the time of grant and revise in subsequent periods if actual forfeitures differ from those estimates. We use the Black-Scholes model to estimate the fair value of stock options granted and stock purchase rights under our ESPP. On the grant date, we use our stock price and assumptions regarding a number of variables to determine the estimated fair value of stock-based payment awards. These variables include, but are not limited to, our expected stock price volatility over the term of the awards, and actual and projected employee stock option exercise behaviors. We recognize compensation expense for stock options granted, RSUs, PRSUs and stock purchase rights under the ESPP using the accelerated multiple-option approach. Under the accelerated multiple-option approach (also known as the graded-vesting method), we recognize compensation expense over the requisite service period for each separately vesting tranche of the award as though the award were in substance multiple awards, which results in the expense being front-loaded over the vesting period. For the three months ended March 31, 2023 and 2022, we used the following weighted-average assumptions in our Black-Scholes calculations: Employee Stock Options: Three Months Ended March 31, 2023 2022 Risk-free interest rate 3.6 % 1.7 % Dividend yield 0.0 % 0.0 % Volatility 47.5 % 55.2 % Expected life* 6.3 years 6.3 years * In 2021, our Compensation Committee approved an amendment to the 2011 Equity Incentive Plan, or 2011 Plan, and the 2020 Equity Incentive Plan, or ESPP: Three Months Ended March 31, 2023 2022 Risk-free interest rate 5.2 % 0.6 % Dividend yield 0.0 % 0.0 % Volatility 36.7 % 50.2 % Expected life 6 months 6 months RSUs: The fair value of RSUs is based on the market price of our common stock on the date of grant. The RSUs we have granted to employees vest annually over a four-year period. The RSUs we granted to our board of directors prior to June 2020 vest annually over a four-year period. The RSUs we granted after June 2020 to our board of directors fully vest after one year. The weighted-average grant date fair value of RSUs granted to employees for the three months ended March 31, 2023 was $39.85 per share. PRSUs: Beginning in 2020, we added PRSU awards to the compensation for our Chief Executive Officer, Dr. Brett Monia. In 2022, we added PRSU awards to the compensation for our other Section 16 officers. Beginning in 2023, we added PRSU awards to the compensation for all executive officers. Under the terms of the PRSUs we granted in 2020 through 2022, one third Under the terms of the PRSUs we granted in 2023, 100 percent of the PRSUs may vest at the end of the three-year performance period based on our relative TSR as compared to a peer group of companies and as measured at the end of the performance period. Under the terms of the grants, no number of PRSUs is guaranteed to vest and the actual number of PRSUs that will vest at the end of each performance period may be anywhere from zero to 200 percent of the target number depending on our relative TSR. We determined the fair value of the PRSUs using a Monte Carlo model because the performance target is based on our relative TSR, which represents a market condition. The weighted-average grant date fair value of PRSUs granted to our executive officers for the three months ended March 31, 2023 and 2022 were $58.99 and $42.28 per share, respectively. The following table summarizes stock-based compensation expense for the three months ended March 31, 2023 and 2022 (in thousands): Three Months Ended March 31, 2023 2022 Cost of sales $ 119 $ 160 Research, development and patent expense 19,567 19,082 Selling, general and administrative expense 7,262 6,994 Total $ 26,948 $ 26,236 As of March 31, 2023, total unrecognized estimated stock-based compensation expense related to non-vested stock options, RSUs and PRSUs was $60.2 million, $79.1 million and $9.5 million, respectively. Our actual expenses may differ from these estimates because we will adjust our unrecognized stock-based compensation expense for future forfeitures, including any PRSUs that do not vest. We expect to recognize the cost of stock-based compensation expense related to our non-vested stock options, RSUs and PRSUs over a weighted average amortization period of 1.4 years, 1.8 years and 2.2 years, respectively.

Income Taxes

Income Taxes	3 Months Ended
	Mar. 31, 2023
Income Taxes [Abstract]
Income Taxes	9. Income Taxes Beginning in 2022, the Tax Cuts and Jobs Act of 2017, or TCJA, requires taxpayers to amortize research and development expenditures over five years pursuant to Internal Revenue Code, or IRC, Section 174. Additionally, we expect to reflect the royalty purchase agreement with Royalty Pharma as a taxable sale, requiring us to include the proceeds from the sale, net of currently deductible issuance costs, as taxable income in 2023. We recorded income tax expense of $11.4 million and $1.1 million for the three months ended March 31, 2023 and 2022, respectively. The increase in income tax expense for the three months ended March 31, 2023, compared to the same period in 2022, relates primarily to the impact of the Royalty Pharma transaction.

Liability Related to Sale of Fu

Liability Related to Sale of Future Royalties	3 Months Ended
	Mar. 31, 2023
Liability Related to Sale of Future Royalties [Abstract]
Liability Related to Sale of Future Royalties	10. Liability Related to Sale of Future Royalties In January 2023, we entered into a royalty purchase agreement with Royalty Pharma to monetize a portion of our future SPINRAZA and pelacarsen royalties we are entitled to under our arrangements with Biogen and Novartis, respectively. As a result, we received an upfront payment of $500 million and we are eligible to receive up to $625 million in additional milestone payments. Under the terms of the agreement, Royalty Pharma will receive 25 percent of our SPINRAZA royalty payments from 2023 through 2027, increasing to 45 percent of royalty payments in 2028, on up to $1.5 billion in annual sales. In addition, Royalty Pharma will receive 25 percent of any future royalty payments on pelacarsen, our medicine in development to treat patients with elevated lipoprotein(a), or Lp(a), and cardiovascular disease. Royalty Pharma’s royalty interest in SPINRAZA will revert to us after total SPINRAZA royalty payments to Royalty Pharma reach either $475 million or $550 million, depending on the timing and occurrence of FDA approval of pelacarsen. We recorded the upfront payment of $500 million as a liability related to the sale of future royalties, net of transaction costs of $10.4 million, which we are amortizing over the estimated life of the arrangement using the effective interest rate method. We recognize royalty revenue in the period in which the counterparty sells the related product and recognizes the related revenue. We record royalty payments made to Royalty Pharma as a reduction of the liability. We estimate the effective interest rate used to record interest expense under this agreement based on the estimate of future royalty payments to Royalty Pharma. As of March 31, 2023, the estimated effective interest rate under the agreement was 13.5 percent. The following is a summary of our liability related to sale of future royalties for the three months ended March 31, 2023 (in thousands): Proceeds from sale of future royalties $ 500,000 Interest expense related to sale of future royalties 15,363 Liability related to sale of future royalties as of March 31, 2023 $ 515,363 Net issuance costs related to sale of future royalties as of March 31, 2023 (10,282 ) Net liability related to sale of future royalties as of March 31, 2023 $ 505,081 There are numerous factors, most of which are not within our control, that could materially impact the amount and timing of royalty payments from Biogen and Novartis, and result in changes to our estimate of future royalty payments to Royalty Pharma. Such factors include, but are not limited to the commercial sales of SPINRAZA, the regulatory approval and commercial sales of pelacarsen, competing products or other significant events.

Convertible Debt

Convertible Debt	3 Months Ended
	Mar. 31, 2023
Convertible Debt [Abstract]
Convertible Debt	11. Convertible Debt 0 Percent Convertible Senior Notes and Call Spread In April 2021, we completed a $632.5 million offering of convertible senior notes. We used a portion of the net proceeds from the issuance of the 0% Notes to repurchase $247.9 million in principal of our 1% Notes for $257.0 million. At March 31, 2023, we had the following 0% 0% Notes Outstanding principal balance $ 632.5 Unamortized debt issuance costs $ 9.5 Maturity date April 2026 Interest rate 0 percent Effective interest rate 0.5 percent Conversion price per share $ 57.84 Effective conversion price per share with call spread $ 76.39 Total shares of common stock subject to conversion 10.9 In conjunction with the April 2021 offering, we entered into a call spread transaction, which was comprised of purchasing note hedges and selling warrants, to minimize the impact of potential economic dilution upon conversion of our 0% 0% 0% 0% 0% 0% 0% 0% We recorded the amount we paid for the note hedges and the amount we received for the warrants in additional paid-in capital in our condensed consolidated balance sheets. Refer to Part IV, Item 15, Note 1 of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2022 for our Call Spread accounting policy. We reassess our ability to continue to classify the note hedges and warrants in shareholders’ equity at each reporting period. 0.125 Percent Convertible Senior Notes and Call Spread At March 31, 2023, we had the following 0.125% Notes outstanding with interest payable semi-annually (in millions except interest rate and price per share data): 0.125% Notes Outstanding principal balance $ 548.8 Unamortized debt issuance costs $ 3.8 Maturity date December 2024 Interest rate 0.125 percent Effective interest rate 0.5 percent Conversion price per share $ 83.28 Effective conversion price per share with call spread $ 123.38 Total shares of common stock subject to conversion 6.6 In conjunction with the issuance of our Notes in December 2019, we entered into a call spread transaction, which was comprised of purchasing note hedges and selling warrants, to minimize the impact of potential economic dilution upon conversion of our . We increased our effective conversion price to $123.38 with the same number of underlying shares as our Notes. The call spread cost us $ million, of which $ million was for the note hedge purchase, offset by $ million we received for selling the warrants. Similar to our , our note hedges are subject to adjustment. Additionally, our note hedges are exercisable upon conversion of the . The note hedges will expire upon maturity of the , or December 2024. The note hedges and warrants are separate transactions and are not part of the terms of our . The holders of the do not have any rights with respect to the note hedges and warrants. We recorded the amount we paid for the note hedges and the amount we received for the warrants in additional paid-in capital in our condensed consolidated balance sheets. We reassess our ability to continue to classify the note hedges and warrants in shareholders’ equity at each reporting period. Other Terms of Convertible Senior Notes The 0% and Notes are convertible under certain conditions, at the option of the note holders. We can settle conversions of the notes, at our election, in cash, shares of our common stock or a combination of both. We may not redeem the notes prior to maturity, and we do not have to provide a sinking fund for them. Holders of the notes may require us to purchase some or all of their notes upon the occurrence of certain fundamental changes, as set forth in the indentures governing the notes, at a purchase price equal to of the principal amount of the notes to be purchased, plus any accrued and unpaid interest.

Legal Proceedings

Legal Proceedings	3 Months Ended
	Mar. 31, 2023
Legal Proceedings [Abstract]
Legal Proceedings	12. Legal Proceedings From time to time, we are involved in legal proceedings arising in the ordinary course of our business. Periodically, we evaluate the status of each legal matter and assess our potential financial exposure. If we consider the potential loss from any legal proceeding to be probable and we can reasonably estimate the amount, we accrue a liability for the estimated loss. The outcome of any proceeding is not determinable in advance. Therefore, we are required to use significant judgment to determine the probability of a loss and whether the amount of the loss is reasonably estimable. Our assessment of a potential liability and the amount of accruals we recorded are based only on the information available to us at the time. As additional information becomes available, we reassess the potential liability related to the legal proceeding and may revise our estimates. On January 19, 2022, a purported stockholder of Ionis filed a stockholder derivative complaint in the Delaware Court of Chancery captioned Leo Shumacher, et al. v. Joseph Loscalzo, et al., C.A. No. 2022-0059, or the Shumacher Action. The complaint names Ionis’ board of directors, or the Board, as defendants and names Ionis as a nominal defendant. The Shumacher Action Plaintiff asserts a breach of fiduciary duty claim against the Board for awarding and receiving allegedly excessive compensation. The Shumacher Action Plaintiff also asserts an unjust enrichment claim against the non-executive directors as a result of the compensation they received. The complaint seeks, among other things, damages, restitution, attorneys’ fees and costs, and such other relief as deemed just and proper by the court. On March 18, 2022, Ionis and the Board moved to dismiss the complaint. On May 24, 2022, the parties entered into a Stipulation and Agreement of Compromise, Settlement and Release. On May 25, 2022, another purported stockholder of Ionis filed a stockholder derivative complaint also in the Delaware Court of Chancery captioned Robert S. Cohen, et al. v. Joseph Loscalzo, et al., C.A. No. 2022-0453, or the Cohen Action. The complaint names the Board as defendants and names Ionis as a nominal defendant. The Cohen Action Plaintiff asserts claims for breach of fiduciary duty, unjust enrichment, aiding and abetting breaches of fiduciary duty, and waste against the Board for awarding and receiving allegedly excessive non-executive director compensation for the years 2018, 2019, and 2020. On June 2, 2022, the Cohen Action Plaintiff filed a motion to consolidate the related Cohen Action and Shumacher Action. On July 5, 2022, the Court denied the motion to consolidate in favor of the settlement pending in the Shumacher Action. On July 18, 2022, Ionis filed a Form 8-K disclosing the pending settlement and attaching the Notice of Pendency of Settlement of Action. On September 21, 2022, the Court held a hearing to consider whether the terms of the settlement should be approved, at which hearing the Cohen Action plaintiff objected to the settlement. At the conclusion of the hearing, the Court declined to approve the settlement and directed the parties to meet and confer on the issue of the scope of the release. On February 7, 2023, the parties entered into an Amended Stipulation and Agreement of Compromise, Settlement and Release, which folded the Cohen Action into the settlement, or the Revised Settlement. The settlement did not have a material impact on our condensed consolidated financial statements. On April 24, 2023, the Court issued an Order and Final Judgment approving the Revised Settlement and dismissing the Shumacher and Cohen Actions, and all claims contained therein, with prejudice. The Order does not contain any admission of wrongdoing by any defendant.

Organization and Basis of Pre_2

Organization and Basis of Presentation (Policies)	3 Months Ended
	Mar. 31, 2023
Organization and Basis of Presentation [Abstract]
Basis of Presentation	We prepared the unaudited interim condensed consolidated financial statements for the three months ended March 31, 2023 and 2022 on the same basis as the audited financial statements for the year ended December 31, 2022. We included all normal recurring adjustments in the financial statements, which we considered necessary for a fair presentation of our financial position at such dates and our operating results and cash flows for those periods. Our operating results for the interim periods may not be indicative of what our operating results will be for the entire year. For more complete financial information, these financial statements, and notes thereto, should be read in conjunction with the audited financial statements for the year ended December 31, 2022 included in our Annual Report on Form 10-K filed with the Securities and Exchange Commission, or SEC.
Consolidation	In our condensed consolidated financial statements, we included the accounts of Ionis Pharmaceuticals, Inc. and the consolidated results of our wholly owned subsidiary, Akcea Therapeutics, Inc. and its wholly owned subsidiaries (“we”, “us” or “our”).
Segment Information	We operate as a single single
Use of Estimates	Use of Estimates We prepare our condensed consolidated financial statements in conformity with accounting principles generally accepted in the United States, or

Significant Accounting Polici_2

Significant Accounting Policies (Policies)	3 Months Ended
	Mar. 31, 2023
Significant Accounting Policies [Abstract]
Liability Related to Sale of Future Royalties	Liability Related to Sale of Future Royalties In January 2023, we entered into a royalty purchase agreement with Royalty Pharma Investments, or Royalty Pharma, to monetize a portion of our future SPINRAZA and pelacarsen royalties we are entitled to under our arrangements with Biogen and Novartis, respectively. Refer to Note 10, Liability Related to Sale of Future Royalties We record upfront payments and milestone payments we receive from the sale of future royalties as a liability, net of transaction costs. We record royalty payments made to Royalty Pharma as a reduction of the liability and amortize the transaction costs over the estimated life of the related royalty stream. We account for the associated interest expense under the effective interest rate method, while continuing to recognize the full amount of royalty revenue in the period in which the counterparty sells the related product and recognizes the related revenue. The liability related to the sale of future royalties, effective interest rate and the related interest expense are calculated using our current estimate of anticipated future royalty payments under the arrangement, which we periodically reassess based on internal projections and information from our partners who are responsible for commercializing the medicines. If there is a material change in our estimate, we will prospectively adjust the liability related to the sale of future royalties, effective interest rate and the related interest expense.
Recently Adopted Accounting Standards	Recently Adopted Accounting Standards We do not expect any recently issued accounting standards to have a material impact to our financial results.

Basic and Diluted Net Loss Pe_2

Basic and Diluted Net Loss Per Share (Policies)	3 Months Ended
	Mar. 31, 2023
Basic and Diluted Net Loss Per Share [Abstract]
Basic and Diluted Net Loss Per Share	Basic net loss per share We calculated our basic net loss per share for the three months ended March 31, 2023 and 2022 by dividing our net loss by our weighted-average number of common shares outstanding during the period. Diluted net loss per share For the three months ended March 31, 2023 and 2022, we incurred a net loss; therefore, we did not include dilutive common equivalent shares in the computation of diluted net loss per share because the effect would have been anti-dilutive. Common stock from the following would have had an anti-dilutive effect on net loss per share: ● 0 percent convertible senior notes, or 0% Notes; ● Note hedges related to the 0% Notes; ● 0.125 percent convertible senior notes, or 0.125% Notes; ● Note hedges related to the 0.125% Notes; ● Dilutive stock options; ● Unvested restricted stock units, or RSUs; ● Unvested performance restricted stock units, or PRSUs; and ● Employee Stock Purchase Plan, or ESPP. Additionally as of March 31, 2023, we had warrants related to our 0% and 0.125% Notes outstanding. We will include the shares issuable under these warrants in our calculation of diluted earnings per share when the average market price per share of our common stock for the reporting period exceeds the strike price of the warrants.

Stock-based Compensation Expe_2

Stock-based Compensation Expense (Policies)	3 Months Ended
	Mar. 31, 2023
Stock-based Compensation Expense [Abstract]
Stock-Based Compensation Expense	We measure stock-based compensation expense for equity-classified awards, principally related to stock options, RSUs, PRSUs and stock purchase rights under our ESPP based on the estimated fair value of the award on the date of grant. We recognize the value of the portion of the award that we ultimately expect to vest as stock-based compensation expense over the requisite service period in our condensed consolidated statements of operations. We reduce stock-based compensation expense for estimated forfeitures at the time of grant and revise in subsequent periods if actual forfeitures differ from those estimates. We use the Black-Scholes model to estimate the fair value of stock options granted and stock purchase rights under our ESPP. On the grant date, we use our stock price and assumptions regarding a number of variables to determine the estimated fair value of stock-based payment awards. These variables include, but are not limited to, our expected stock price volatility over the term of the awards, and actual and projected employee stock option exercise behaviors. We recognize compensation expense for stock options granted, RSUs, PRSUs and stock purchase rights under the ESPP using the accelerated multiple-option approach. Under the accelerated multiple-option approach (also known as the graded-vesting method), we recognize compensation expense over the requisite service period for each separately vesting tranche of the award as though the award were in substance multiple awards, which results in the expense being front-loaded over the vesting period.

Supplemental Financial Data (Ta

Supplemental Financial Data (Tables)	3 Months Ended
	Mar. 31, 2023
Supplemental Financial Data [Abstract]
Inventories	Inventories Our inventory consisted of the following (in thousands): March 31, 2023 December 31, 2022 Raw materials: Raw materials - clinical $ 17,356 $ 17,061 Raw materials - commercial 2,786 2,699 Total raw materials 20,142 19,760 Work in process 1,840 2,109 Finished goods 218 164 Total inventory $ 22,200 $ 22,033
Accrued Liabilities	Accrued Liabilities Our accrued liabilities consisted of the following (in thousands): March 31, 2023 December 31, 2022 Clinical development expenses $ 85,694 $ 116,460 In-licensing expenses 12,704 7,945 Commercial expenses 4,704 3,498 Other miscellaneous expenses 9,600 12,198 Total accrued liabilities $ 112,702 $ 140,101

Collaborative Arrangements an_2

Collaborative Arrangements and Licensing Agreements (Tables)	3 Months Ended
	Mar. 31, 2023
Biogen [Member]
Collaborative Arrangements and Licensing Agreements [Abstract]
Revenue from Collaborative Relationship	During the three months ended March 31, 2023 and 2022, we earned the following revenue from our relationship with Biogen (in thousands, except percentage amounts): Three Months Ended March 31, 2023 2022 SPINRAZA royalties (commercial revenue) $ 50,247 $ 53,818 R&D revenue 20,254 40,049 Total revenue from our relationship with Biogen $ 70,501 $ 93,867 Percentage of total revenue 54 % 66 %
GSK [Member]
Collaborative Arrangements and Licensing Agreements [Abstract]
Revenue from Collaborative Relationship	During the three months ended March 31, 2023 and 2022, we earned the following revenue from our relationship with GSK (in thousands, except percentage amounts): Three Months Ended March 31, 2023 2022 R&D revenue $ 15,000 $ — Percentage of total revenue 11 % —

Investments (Tables)

Investments (Tables)	3 Months Ended
	Mar. 31, 2023
Investments [Abstract]
Contract Maturity of Available-for-Sale Securities	The following table summarizes the contract maturity of the available-for-sale securities we held as of March 31, 2023: One year 74 % After one year two years 23 % After two years three and a half years 3 % Total 100 %
Summary of Investments	The following is a summary of our investments (in thousands): Amortized Gross Unrealized Estimated March 31, 2023 Cost Gains Losses Fair Value Available-for-sale debt securities: Corporate debt securities (1) $ 623,940 $ 62 $ (6,026 ) $ 617,976 Debt securities issued by U.S. government agencies 247,629 69 (1,283 ) 246,415 Debt securities issued by the U.S. Treasury (1) 556,394 62 (3,738 ) 552,718 Debt securities issued by states of the U.S. and political subdivisions of the states 57,322 4 (498 ) 56,828 Total debt securities with a maturity of one year or less 1,485,285 197 (11,545 ) 1,473,937 Corporate debt securities 200,661 336 (5,205 ) 195,792 Debt securities issued by U.S. government agencies 99,635 256 (649 ) 99,242 Debt securities issued by the U.S. Treasury 257,651 364 (2,726 ) 255,289 Debt securities issued by states of the U.S. and political subdivisions of the states 14,564 106 (182 ) 14,488 Total debt securities with a maturity of more than one year 572,511 1,062 (8,762 ) 564,811 Total available-for-sale debt securities $ 2,057,796 $ 1,259 $ (20,307 ) $ 2,038,748 Equity securities: Publicly traded equity securities included in other current assets (2) $ 11,897 $ — $ (4,508 ) $ 7,389 Privately held equity securities included in deposits and other assets (3) 23,115 25,001 (5,125 ) 42,991 Total equity securities 35,012 25,001 (9,633 ) 50,380 Total available-for-sale debt and equity securities $ 2,092,808 $ 26,260 $ (29,940 ) $ 2,089,128 Amortized Gross Unrealized Estimated December 31, 2022 Cost Gains Losses Fair Value Available-for-sale debt securities: Corporate debt securities (1) $ 513,790 $ 23 $ (4,365 ) $ 509,448 Debt securities issued by U.S. government agencies 133,585 — (1,829 ) 131,756 Debt securities issued by the U.S. Treasury (1) 512,655 23 (5,124 ) 507,554 Debt securities issued by states of the U.S. and political subdivisions of the states 57,484 18 (686 ) 56,816 Other municipal debt securities 6,008 — (14 ) 5,994 Total debt securities with a maturity of one year or less 1,223,522 64 (12,018 ) 1,211,568 Corporate debt securities 227,631 14 (10,143 ) 217,502 Debt securities issued by U.S. government agencies 34,339 — (1,040 ) 33,299 Debt securities issued by the U.S. Treasury 245,030 — (4,109 ) 240,921 Debt securities issued by states of the U.S. and political subdivisions of the states 18,314 116 (329 ) 18,101 Total debt securities with a maturity of more than one year 525,314 130 (15,621 ) 509,823 Total available-for-sale debt securities $ 1,748,836 $ 194 $ (27,639 ) $ 1,721,391 Equity securities: Publicly traded equity securities included in other current assets (2) $ 11,897 $ — $ (1,358 ) $ 10,539 Privately held equity securities included in deposits and other assets (3) 23,115 17,257 — 40,372 Total equity securities 35,012 17,257 (1,358 ) 50,911 Total available-for-sale debt and equity securities $ 1,783,848 $ 17,451 $ (28,997 ) $ 1,772,302 (1) Includes investments classified as cash equivalents in our condensed consolidated balance sheets. (2) Our publicly traded equity securities are included in other current assets. We recognize publicly traded equity securities at fair value. In the three months ended March 31, 2023, we recognized a $3.2 million unrealized loss in our condensed consolidated statements of operations related to a decrease in the fair value of our investments in publicly traded companies. (3) Our privately held equity securities are included in deposits and other assets. We recognize our privately held equity securities at . In the three months ended March 31, 2023, we recorded a net gain of $ million in our condensed consolidated statements of operations related to changes in the fair value of our investments in privately held companies.
Temporarily Impaired Investments	The following is a summary of our investments we consider to be temporarily impaired at March 31, 2023 (in thousands, except for number of investments): Less than 12 Months of Temporary Impairment More than 12 Months of Temporary Impairment Total Temporary Impairment Number of Investments Estimated Fair Value Unrealized Losses Estimated Fair Value Unrealized Losses Estimated Fair Value Unrealized Losses Corporate debt securities 361 $ 434,500 $ (1,697 ) $ 291,713 $ (9,534 ) $ 726,213 $ (11,231 ) Debt securities issued by U.S. government agencies 68 138,211 (424 ) 70,965 (1,508 ) 209,176 (1,932 ) Debt securities issued by the U.S. Treasury 64 603,444 (3,873 ) 91,448 (2,591 ) 694,892 (6,464 ) Debt securities issued by states of the U.S. and political subdivisions of the states 110 22,778 (140 ) 32,792 (540 ) 55,570 (680 ) Total temporarily impaired securities 603 $ 1,198,933 $ (6,134 ) $ 486,918 $ (14,173 ) $ 1,685,851 $ (20,307 )

Fair Value Measurements (Tables

Fair Value Measurements (Tables)	3 Months Ended
	Mar. 31, 2023
Fair Value Measurements [Abstract]
Assets Measured at Fair Value on a Recurring Basis	The following tables present the major security types we held at March 31, 2023 and December 31, 2022 that we regularly measure and carry at fair value. The following tables segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective security’s fair value (in thousands): At March 31, 2023 Quoted Prices in Active Markets (Level 1) Significant Other Observable Inputs (Level 2) Cash equivalents (1) $ 276,352 $ 276,352 $ — Corporate debt securities (2) 813,768 — 813,768 Debt securities issued by U.S. government agencies (2) 345,657 — 345,657 Debt securities issued by the U.S. Treasury (2) 808,007 808,007 — Debt securities issued by states of the U.S. and political subdivisions of the states (3) 71,316 — 71,316 Publicly traded equity securities included in other current assets (4) 7,389 7,389 — Total $ 2,322,489 $ 1,091,748 $ 1,230,741 At December 31, 2022 Quoted Prices in Active Markets (Level 1) Significant Other Observable Inputs (Level 2) Cash equivalents (1) $ 211,655 $ 211,655 $ — Corporate debt securities (5) 726,950 — 726,950 Debt securities issued by U.S. government agencies (2) 165,055 — 165,055 Debt securities issued by the U.S. Treasury (2) 748,475 748,475 — Debt securities issued by states of the U.S. and political subdivisions of the states (2) 74,917 — 74,917 Other municipal debt securities (2) 5,994 — 5,994 Publicly traded equity securities included in other current assets (4) 10,539 10,539 — Total $ 1,943,585 $ 970,669 $ 972,916 The following footnotes reference lines in our condensed consolidated balance sheets: (1) Included in cash and cash equivalents in our condensed consolidated balance sheets. (2) Included in short-term investments in our condensed consolidated balance sheets. (3) $1.0 million was included in cash and cash equivalents in our condensed consolidated balance sheets, with the difference included in short-term investments in our condensed consolidated balance sheets. (4) Included in other current assets in our condensed consolidated balance sheets. (5) $11.0 million was included in cash and cash equivalents in our condensed consolidated balance sheets, with the difference included in short-term investments in our condensed consolidated balance sheets.

Stock-based Compensation Expe_3

Stock-based Compensation Expense (Tables)	3 Months Ended
	Mar. 31, 2023
Stock-based Compensation Expense [Abstract]
Weighted-Average Assumptions for Stock Options	Employee Stock Options: Three Months Ended March 31, 2023 2022 Risk-free interest rate 3.6 % 1.7 % Dividend yield 0.0 % 0.0 % Volatility 47.5 % 55.2 % Expected life* 6.3 years 6.3 years * In 2021, our Compensation Committee approved an amendment to the 2011 Equity Incentive Plan, or 2011 Plan, and the 2020 Equity Incentive Plan, or
Weighted-Average Assumptions for ESPP	ESPP: Three Months Ended March 31, 2023 2022 Risk-free interest rate 5.2 % 0.6 % Dividend yield 0.0 % 0.0 % Volatility 36.7 % 50.2 % Expected life 6 months 6 months
Stock-Based Compensation Expense	The following table summarizes stock-based compensation expense for the three months ended March 31, 2023 and 2022 (in thousands): Three Months Ended March 31, 2023 2022 Cost of sales $ 119 $ 160 Research, development and patent expense 19,567 19,082 Selling, general and administrative expense 7,262 6,994 Total $ 26,948 $ 26,236

Liability Related to Sale of _2

Liability Related to Sale of Future Royalties (Tables)	3 Months Ended
	Mar. 31, 2023
Liability Related to Sale of Future Royalties [Abstract]
Liability Related to Sale of Future Royalties	The following is a summary of our liability related to sale of future royalties for the three months ended March 31, 2023 (in thousands): Proceeds from sale of future royalties $ 500,000 Interest expense related to sale of future royalties 15,363 Liability related to sale of future royalties as of March 31, 2023 $ 515,363 Net issuance costs related to sale of future royalties as of March 31, 2023 (10,282 ) Net liability related to sale of future royalties as of March 31, 2023 $ 505,081

Convertible Debt (Tables)

Convertible Debt (Tables)	3 Months Ended
	Mar. 31, 2023
0% Notes [Member]
Convertible Notes [Abstract]
Convertible Senior Notes	At March 31, 2023, we had the following 0% 0% Notes Outstanding principal balance $ 632.5 Unamortized debt issuance costs $ 9.5 Maturity date April 2026 Interest rate 0 percent Effective interest rate 0.5 percent Conversion price per share $ 57.84 Effective conversion price per share with call spread $ 76.39 Total shares of common stock subject to conversion 10.9
0.125% Notes [Member]
Convertible Notes [Abstract]
Convertible Senior Notes	At March 31, 2023, we had the following 0.125% Notes outstanding with interest payable semi-annually (in millions except interest rate and price per share data): 0.125% Notes Outstanding principal balance $ 548.8 Unamortized debt issuance costs $ 3.8 Maturity date December 2024 Interest rate 0.125 percent Effective interest rate 0.5 percent Conversion price per share $ 83.28 Effective conversion price per share with call spread $ 123.38 Total shares of common stock subject to conversion 6.6

Organization and Basis of Pre_3

Organization and Basis of Presentation (Details)	3 Months Ended
	Mar. 31, 2023 Segment
Organization and Basis of Presentation [Abstract]
Number of operating segments	1

Supplemental Financial Data, In

Supplemental Financial Data, Inventories (Details) - USD ($) $ in Thousands	Mar. 31, 2023	Dec. 31, 2022
Inventory [Abstract]
Raw materials	$ 20,142	$ 19,760
Work in process	1,840	2,109
Finished goods	218	164
Total inventory	22,200	22,033
Clinical [Member]
Inventory [Abstract]
Raw materials	17,356	17,061
Commercial [Member]
Inventory [Abstract]
Raw materials	$ 2,786	$ 2,699

Supplemental Financial Data, Ac

Supplemental Financial Data, Accrued Liabilities (Details) - USD ($) $ in Thousands	Mar. 31, 2023	Dec. 31, 2022
Accrued Liabilities [Abstract]
Clinical development expenses	$ 85,694	$ 116,460
In-licensing expenses	12,704	7,945
Commercial expenses	4,704	3,498
Other miscellaneous expenses	9,600	12,198
Total accrued liabilities	$ 112,702	$ 140,101

Collaborative Arrangements an_3

Collaborative Arrangements and Licensing Agreements, Biogen (Details) - USD ($) $ in Thousands	1 Months Ended	3 Months Ended
	Apr. 30, 2023	Mar. 31, 2023	Mar. 31, 2022	Dec. 31, 2022
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue		$ 130,524	$ 141,919
SPINRAZA Royalties [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue		50,247	53,818
R&D Revenue [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue		62,756	69,634
Biogen Collaborations [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue		70,501	$ 93,867
Deferred revenue		$ 340,900		$ 351,200
Biogen Collaborations [Member] | Revenue [Member] | Strategic Partner [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Concentration percentage		54%	66%
Biogen Collaborations [Member] | Minimum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative payments received		$ 3,500,000
Biogen Collaborations [Member] | SPINRAZA Royalties [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue		50,247	$ 53,818
Biogen Collaborations [Member] | R&D Revenue [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue		20,254	$ 40,049
2012 Neurology [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Milestone payment earned		10,000
2012 Neurology [Member] | Maximum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Next payment to be achieved		$ 25,000
2013 Strategic Neurology [Member] | Maximum [Member] | Subsequent Event [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Next payment to be achieved	$ 20,000
2013 Strategic Neurology [Member] | Tofersen [Member] | Subsequent Event [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue	$ 16,000

Collaborative Arrangements an_4

Collaborative Arrangements and Licensing Agreements, GSK (Details) - USD ($) $ in Thousands	3 Months Ended
	Mar. 31, 2023	Mar. 31, 2022	Dec. 31, 2022
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue	$ 130,524	$ 141,919
R&D Revenue [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue	62,756	$ 69,634
GSK [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Next payment to be achieved	15,000
Deferred revenue	$ 0		$ 0
GSK [Member] | Revenue [Member] | Strategic Partner [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Concentration percentage	11%	0%
GSK [Member] | Minimum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative payments received	$ 105,000
GSK [Member] | R&D Revenue [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue	15,000	$ 0
GSK [Member] | Bepirovirsen [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue	$ 15,000

Basic and Diluted Net Loss Pe_3

Basic and Diluted Net Loss Per Share (Details)	Mar. 31, 2023	Dec. 31, 2022	Mar. 31, 2022
0% Notes [Member]
Diluted Net Loss per Share [Abstract]
Interest rate on convertible senior notes	0%	0%	0%
0.125% Notes [Member]
Diluted Net Loss per Share [Abstract]
Interest rate on convertible senior notes	0.125%	0.125%	0.125%

Investments, Contract Maturity

Investments, Contract Maturity of Available-for-Sale Securities (Details)	3 Months Ended
	Mar. 31, 2023
Contract Maturity of Available-for-Sale Securities [Abstract]
One year or less	74%
After one year but within two years	23%
After two years but within three and a half years	3%
Total	100%
Maximum contract maturity period, range 1	1 year
Maximum contract maturity period, range 2	2 years
Maximum contract maturity period, range 3	3 years 6 months
Percentage of available-for-sale securities with a maturity of less than two years	97%

Investments, Summary of Investm

Investments, Summary of Investments (Details) $ in Thousands		3 Months Ended
		Mar. 31, 2023 USD ($) Company	Dec. 31, 2022 USD ($)
Ownership Interests in Private and Public Companies [Abstract]
Number of private companies in which there is an equity ownership interest of less than 20% | Company		7
Number of public companies in which there is an equity ownership interest of less than 20% | Company		3
Available-for-sale Debt Securities with Maturity of One Year or Less [Abstract]
Amortized cost		$ 1,485,285	$ 1,223,522
Gross unrealized gains		197	64
Gross unrealized losses		(11,545)	(12,018)
Estimated fair value		1,473,937	1,211,568
Available-for-sale Debt Securities with Maturity of More Than One Year [Abstract]
Amortized cost		572,511	525,314
Gross unrealized gains		1,062	130
Gross unrealized losses		(8,762)	(15,621)
Estimated fair value		564,811	509,823
Available-for-sale Debt Securities [Abstract]
Amortized cost		2,057,796	1,748,836
Gross unrealized gains		1,259	194
Gross unrealized losses		(20,307)	(27,639)
Estimated fair value		2,038,748	1,721,391
Equity Securities [Abstract]
Amortized cost		35,012	35,012
Gross unrealized gains		25,001	17,257
Gross unrealized losses		(9,633)	(1,358)
Estimated fair value		50,380	50,911
Available-for-sale Debt and Equity Securities [Abstract]
Amortized cost		2,092,808	1,783,848
Gross unrealized gains		26,260	17,451
Gross unrealized losses		(29,940)	(28,997)
Estimated fair value		2,089,128	1,772,302
Corporate Debt Securities [Member]
Available-for-sale Debt Securities with Maturity of One Year or Less [Abstract]
Amortized cost	[1]	623,940	513,790
Gross unrealized gains		62	23
Gross unrealized losses		(6,026)	(4,365)
Estimated fair value		617,976	509,448
Available-for-sale Debt Securities with Maturity of More Than One Year [Abstract]
Amortized cost		200,661	227,631
Gross unrealized gains		336	14
Gross unrealized losses		(5,205)	(10,143)
Estimated fair value		195,792	217,502
Debt Securities Issued by U.S. Government Agencies [Member]
Available-for-sale Debt Securities with Maturity of One Year or Less [Abstract]
Amortized cost		247,629	133,585
Gross unrealized gains		69	0
Gross unrealized losses		(1,283)	(1,829)
Estimated fair value		246,415	131,756
Available-for-sale Debt Securities with Maturity of More Than One Year [Abstract]
Amortized cost		99,635	34,339
Gross unrealized gains		256	0
Gross unrealized losses		(649)	(1,040)
Estimated fair value		99,242	33,299
Debt Securities Issued by the U.S. Treasury [Member]
Available-for-sale Debt Securities with Maturity of One Year or Less [Abstract]
Amortized cost	[1]	556,394	512,655
Gross unrealized gains		62	23
Gross unrealized losses		(3,738)	(5,124)
Estimated fair value		552,718	507,554
Available-for-sale Debt Securities with Maturity of More Than One Year [Abstract]
Amortized cost		257,651	245,030
Gross unrealized gains		364	0
Gross unrealized losses		(2,726)	(4,109)
Estimated fair value		255,289	240,921
Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member]
Available-for-sale Debt Securities with Maturity of One Year or Less [Abstract]
Amortized cost		57,322	57,484
Gross unrealized gains		4	18
Gross unrealized losses		(498)	(686)
Estimated fair value		56,828	56,816
Available-for-sale Debt Securities with Maturity of More Than One Year [Abstract]
Amortized cost		14,564	18,314
Gross unrealized gains		106	116
Gross unrealized losses		(182)	(329)
Estimated fair value		14,488	18,101
Other Municipal Debt Securities [Member]
Available-for-sale Debt Securities with Maturity of One Year or Less [Abstract]
Amortized cost			6,008
Gross unrealized gains			0
Gross unrealized losses			(14)
Estimated fair value			5,994
Publicly Traded Equity Securities [Member]
Equity Securities [Abstract]
Amortized cost	[2]	11,897	11,897
Gross unrealized gains		0	0
Gross unrealized losses		(4,508)	(1,358)
Estimated fair value		7,389	10,539
Available-for-sale Debt and Equity Securities [Abstract]
Unrealized loss on equity securities		(3,200)
Privately Held Equity Securities [Member]
Equity Securities [Abstract]
Amortized cost	[3]	23,115	23,115
Gross unrealized gains		25,001	17,257
Gross unrealized losses		(5,125)	0
Estimated fair value		42,991	$ 40,372
Available-for-sale Debt and Equity Securities [Abstract]
Unrealized gain on equity securities		$ 2,600
[1]Includes investments classified as cash equivalents in our condensed consolidated balance sheets.[2]Our publicly traded equity securities are included in other current assets. We recognize publicly traded equity securities at fair value. In the three months ended March 31, 2023, we recognized a $3.2 million unrealized loss in our condensed consolidated statements of operations related to a decrease in the fair value of our investments in publicly traded companies.[3] Our privately held equity securities are included in deposits and other assets. We recognize our privately held equity securities at . In the three months ended March 31, 2023, we recorded a net gain of $ million in our condensed consolidated statements of operations related to changes in the fair value of our investments in privately held companies.

Investments, Investments Tempor

Investments, Investments Temporarily Impaired (Details) $ in Thousands	Mar. 31, 2023 USD ($) Investment
Temporarily Impaired Investments [Abstract]
Number of investments | Investment	603
Estimated Fair Value [Abstract]
Less than 12 months of temporary impairment	$ 1,198,933
More than 12 months of temporary impairment	486,918
Total temporary impairment	1,685,851
Unrealized Losses [Abstract]
Less than 12 months of temporary impairment	(6,134)
More than 12 months of temporary impairment	(14,173)
Total temporary impairment	$ (20,307)
Corporate Debt Securities [Member]
Temporarily Impaired Investments [Abstract]
Number of investments | Investment	361
Estimated Fair Value [Abstract]
Less than 12 months of temporary impairment	$ 434,500
More than 12 months of temporary impairment	291,713
Total temporary impairment	726,213
Unrealized Losses [Abstract]
Less than 12 months of temporary impairment	(1,697)
More than 12 months of temporary impairment	(9,534)
Total temporary impairment	$ (11,231)
Debt Securities Issued by U.S. Government Agencies [Member]
Temporarily Impaired Investments [Abstract]
Number of investments | Investment	68
Estimated Fair Value [Abstract]
Less than 12 months of temporary impairment	$ 138,211
More than 12 months of temporary impairment	70,965
Total temporary impairment	209,176
Unrealized Losses [Abstract]
Less than 12 months of temporary impairment	(424)
More than 12 months of temporary impairment	(1,508)
Total temporary impairment	$ (1,932)
Debt Securities Issued by the U.S. Treasury [Member]
Temporarily Impaired Investments [Abstract]
Number of investments | Investment	64
Estimated Fair Value [Abstract]
Less than 12 months of temporary impairment	$ 603,444
More than 12 months of temporary impairment	91,448
Total temporary impairment	694,892
Unrealized Losses [Abstract]
Less than 12 months of temporary impairment	(3,873)
More than 12 months of temporary impairment	(2,591)
Total temporary impairment	$ (6,464)
Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member]
Temporarily Impaired Investments [Abstract]
Number of investments | Investment	110
Estimated Fair Value [Abstract]
Less than 12 months of temporary impairment	$ 22,778
More than 12 months of temporary impairment	32,792
Total temporary impairment	55,570
Unrealized Losses [Abstract]
Less than 12 months of temporary impairment	(140)
More than 12 months of temporary impairment	(540)
Total temporary impairment	$ (680)

Fair Value Measurements (Detail

Fair Value Measurements (Details) - USD ($) $ in Thousands		Mar. 31, 2023		Dec. 31, 2022		Mar. 31, 2022
Fair Value Measurements [Abstract]
Available-for-sale securities		$ 2,038,748		$ 1,721,391
Equity securities		$ 50,380		$ 50,911
0.125% Notes [Member]
Fair Value Measurements [Abstract]
Interest rate on convertible senior notes		0.125%		0.125%		0.125%
0% Notes [Member]
Fair Value Measurements [Abstract]
Interest rate on convertible senior notes		0%		0%		0%
Publicly Traded Equity Securities [Member]
Fair Value Measurements [Abstract]
Equity securities		$ 7,389		$ 10,539
Recurring Basis [Member]
Fair Value Measurements [Abstract]
Cash equivalents	[1]	276,352		211,655
Total		2,322,489		1,943,585
Recurring Basis [Member] | Corporate Debt Securities [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		813,768	[2]	726,950	[3]
Recurring Basis [Member] | Corporate Debt Securities [Member] | Cash and Cash Equivalents [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities				11,000
Recurring Basis [Member] | Debt Securities Issued by U.S. Government Agencies [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities	[2]	345,657		165,055
Recurring Basis [Member] | Debt Securities Issued by the U.S. Treasury [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities	[2]	808,007		748,475
Recurring Basis [Member] | Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		71,316	[4]	74,917	[2]
Recurring Basis [Member] | Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member] | Cash and Cash Equivalents [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		1,000
Recurring Basis [Member] | Other Municipal Debt Securities [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities	[2]			5,994
Recurring Basis [Member] | Publicly Traded Equity Securities [Member] | Other Current Assets [Member]
Fair Value Measurements [Abstract]
Equity securities	[5]	7,389		10,539
Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member]
Fair Value Measurements [Abstract]
Cash equivalents		276,352		211,655
Total		1,091,748		970,669
Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Corporate Debt Securities [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		0		0
Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Debt Securities Issued by U.S. Government Agencies [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		0		0
Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Debt Securities Issued by the U.S. Treasury [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		808,007		748,475
Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		0		0
Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Other Municipal Debt Securities [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities				0
Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Publicly Traded Equity Securities [Member]
Fair Value Measurements [Abstract]
Equity securities		7,389		10,539
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member]
Fair Value Measurements [Abstract]
Cash equivalents		0		0
Total		1,230,741		972,916
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | 0.125% Notes [Member]
Fair Value Measurements [Abstract]
Convertible notes		506,300		498,900
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | 0% Notes [Member]
Fair Value Measurements [Abstract]
Convertible notes		578,400		587,300
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Corporate Debt Securities [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		813,768		726,950
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Debt Securities Issued by U.S. Government Agencies [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		345,657		165,055
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Debt Securities Issued by the U.S. Treasury [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		0		0
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		71,316		74,917
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Other Municipal Debt Securities [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities				5,994
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Publicly Traded Equity Securities [Member]
Fair Value Measurements [Abstract]
Equity securities		$ 0		$ 0
[1]Included in cash and cash equivalents in our condensed consolidated balance sheets.[2]Included in short-term investments in our condensed consolidated balance sheets.[3]$11.0 million was included in cash and cash equivalents in our condensed consolidated balance sheets, with the difference included in short-term investments in our condensed consolidated balance sheets.[4]$1.0 million was included in cash and cash equivalents in our condensed consolidated balance sheets, with the difference included in short-term investments in our condensed consolidated balance sheets.[5]Included in other current assets in our condensed consolidated balance sheets.

Stock-based Compensation Expe_4

Stock-based Compensation Expense (Details) $ / shares in Units, $ in Thousands		3 Months Ended
		Mar. 31, 2023 USD ($) Period $ / shares shares	Mar. 31, 2022 USD ($) $ / shares
Stock-based Compensation Expense [Abstract]
Stock-based compensation expense		$ 26,948	$ 26,236
Cost of Sales [Member]
Stock-based Compensation Expense [Abstract]
Stock-based compensation expense		119	160
Research, Development and Patent Expense [Member]
Stock-based Compensation Expense [Abstract]
Stock-based compensation expense		19,567	19,082
Selling, General and Administrative Expense [Member]
Stock-based Compensation Expense [Abstract]
Stock-based compensation expense		7,262	$ 6,994
Stock Options [Member]
Unrecognized Compensation Expense [Abstract]
Unrecognized compensation expense related to non-vested stock options		$ 60,200
Weighted average period for recognition		1 year 4 months 24 days
Stock Options [Member] | Employees [Member]
Weighted-Average Assumptions [Abstract]
Risk-free interest rate		3.60%	1.70%
Dividend yield		0%	0%
Volatility		47.50%	55.20%
Expected life	[1]	6 years 3 months 18 days	6 years 3 months 18 days
Stock Options Granted Prior to January 1, 2022 [Member]
Weighted-Average Assumptions [Abstract]
Award term		7 years
Stock Options Granted on January 1, 2022 and Thereafter [Member]
Weighted-Average Assumptions [Abstract]
Award term		10 years
ESPP [Member]
Weighted-Average Assumptions [Abstract]
Risk-free interest rate		5.20%	0.60%
Dividend yield		0%	0%
Volatility		36.70%	50.20%
Expected life		6 months	6 months
RSUs [Member]
Unrecognized Compensation Expense [Abstract]
Unrecognized compensation cost related to non-vested units		$ 79,100
Weighted average period for recognition		1 year 9 months 18 days
RSUs [Member] | Board of Directors [Member] | Minimum [Member]
RSUs and PRSUs [Abstract]
Vesting period		1 year
RSUs [Member] | Board of Directors [Member] | Maximum [Member]
RSUs and PRSUs [Abstract]
Vesting period		4 years
RSUs [Member] | Employees [Member]
RSUs and PRSUs [Abstract]
Vesting period		4 years
Weighted-average grant date fair value (in dollars per share) | $ / shares		$ 39.85
PRSUs [Member]
Unrecognized Compensation Expense [Abstract]
Unrecognized compensation cost related to non-vested units		$ 9,500
Weighted average period for recognition		2 years 2 months 12 days
PRSUs [Member] | Section 16 Officers [Member]
RSUs and PRSUs [Abstract]
Number of performance periods | Period		3
Vesting period		3 years
Number of units guaranteed to vest (in shares) | shares		0
Weighted-average grant date fair value (in dollars per share) | $ / shares		$ 58.99	$ 42.28
PRSUs [Member] | Section 16 Officers [Member] | Minimum [Member]
RSUs and PRSUs [Abstract]
Percentage of units guaranteed to vest		0%
PRSUs [Member] | Section 16 Officers [Member] | Maximum [Member]
RSUs and PRSUs [Abstract]
Percentage of units guaranteed to vest		150%
PRSUs [Member] | Section 16 Officers [Member] | One-Year Period [Member]
RSUs and PRSUs [Abstract]
Vesting percentage		33.30%
PRSUs [Member] | Section 16 Officers [Member] | Two-Year Period [Member]
RSUs and PRSUs [Abstract]
Vesting percentage		33.30%
PRSUs [Member] | Section 16 Officers [Member] | Three-Year Period [Member]
RSUs and PRSUs [Abstract]
Vesting percentage		33.30%
[1]In 2021, our Compensation Committee approved an amendment to the 2011 Equity Incentive Plan, or 2011 Plan, and the 2020 Equity Incentive Plan, or

Income Taxes (Details)

Income Taxes (Details) - USD ($) $ in Thousands	3 Months Ended
	Mar. 31, 2023	Mar. 31, 2022
Income Taxes [Abstract]
Income tax expense	$ 11,380	$ 1,094

Liability Related to Sale of _3

Liability Related to Sale of Future Royalties (Details) - USD ($) $ in Thousands	1 Months Ended	3 Months Ended
	Jan. 31, 2023	Mar. 31, 2023	Mar. 31, 2022
Royalty Revenue Monetization [Abstract]
Transaction costs		$ 10,434	$ 0
Proceeds from sale of future royalties		500,000	0
Interest expense related to sale of future royalties		15,363	$ 0
Net liability related to sale of future royalties		505,081
Royalty Purchase Agreement [Member]
Royalty Revenue Monetization [Abstract]
Upfront payment received	$ 500,000
Maximum amount of payments receivable for additional milestones		$ 625,000
Effective interest rate		13.50%
Transaction costs		$ 10,400
Proceeds from sale of future royalties		500,000
Interest expense related to sale of future royalties		15,363
Liability related to sale of future royalties as of		515,363
Net issuance costs related to sale of future royalties		(10,282)
Net liability related to sale of future royalties		505,081
Royalty Purchase Agreement [Member] | SPINRAZA [Member]
Royalty Revenue Monetization [Abstract]
Maximum amount of annual sales on which royalty payments are paid		$ 1,500,000
Royalty Purchase Agreement [Member] | SPINRAZA [Member] | Minimum [Member]
Royalty Revenue Monetization [Abstract]
Percentage of royalty payments paid on annual sales of medicine		25%
Maximum royalty payments made before royalty interest reverts back		$ 475,000
Royalty Purchase Agreement [Member] | SPINRAZA [Member] | Maximum [Member]
Royalty Revenue Monetization [Abstract]
Percentage of royalty payments paid on annual sales of medicine		45%
Maximum royalty payments made before royalty interest reverts back		$ 550,000
Royalty Purchase Agreement [Member] | Pelacarsen [Member]
Royalty Revenue Monetization [Abstract]
Percentage of royalty payments paid on annual sales of medicine		25%

Convertible Debt (Details)

Convertible Debt (Details) - USD ($) $ / shares in Units, shares in Millions, $ in Millions	1 Months Ended		3 Months Ended
	Apr. 30, 2021	Dec. 31, 2019	Mar. 31, 2023	Dec. 31, 2022	Mar. 31, 2022
0% Notes [Member]
Convertible Debt [Abstract]
Face amount of offering	$ 632.5
Outstanding principal balance			$ 632.5
Unamortized debt issuance costs			$ 9.5
Maturity date			Apr. 30, 2026
Interest rate			0%	0%	0%
Effective interest rate			0.50%
Conversion price per share (in dollars per share)			$ 57.84
Effective conversion price per share with call spread (in dollars per share)			$ 76.39
Total shares of common stock subject to conversion (in shares)			10.9
Cost of call spread	46.9
Purchase of note hedges	136.7
Proceeds from issuance of warrants	89.8
Percentage of principal amount used as purchase price upon occurrence of fundamental change			100%
1% Notes [Member]
Convertible Debt [Abstract]
Principal amount repurchased	247.9
Repurchase of convertible notes	$ 257
Interest rate			1%
0.125% Notes [Member]
Convertible Debt [Abstract]
Outstanding principal balance			$ 548.8
Unamortized debt issuance costs			$ 3.8
Maturity date			Dec. 31, 2024
Interest rate			0.125%	0.125%	0.125%
Effective interest rate			0.50%
Conversion price per share (in dollars per share)			$ 83.28
Effective conversion price per share with call spread (in dollars per share)			$ 123.38
Total shares of common stock subject to conversion (in shares)			6.6
Cost of call spread		$ 52.6
Purchase of note hedges		108.7
Proceeds from issuance of warrants		$ 56.1
Percentage of principal amount used as purchase price upon occurrence of fundamental change			100%