Ionis Pharmaceuticals (IONS) 10-Q 9 Aug 23 2023 Q2 Quarterly report Financial data

Document and Entity Information

Document and Entity Information - shares	6 Months Ended
	Jun. 30, 2023	Aug. 03, 2023
Cover [Abstract]
Document Type	10-Q
Amendment Flag	false
Document Quarterly Report	true
Document Period End Date	Jun. 30, 2023
Current Fiscal Year End Date	--12-31
Document Fiscal Year Focus	2023
Document Fiscal Period Focus	Q2
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		143,326,208

CONDENSED CONSOLIDATED BALANCE

CONDENSED CONSOLIDATED BALANCE SHEETS - USD ($) $ in Thousands	Jun. 30, 2023	Dec. 31, 2022
Current assets:
Cash and cash equivalents	$ 424,790	$ 276,472
Short-term investments	1,960,598	1,710,397
Contracts receivable	27,956	25,538
Inventories	25,538	22,033
Other current assets	177,872	168,254
Total current assets	2,616,754	2,202,694
Property, plant and equipment, net	91,634	74,294
Right-of-use assets	176,718	181,544
Deposits and other assets	86,025	75,344
Total assets	2,971,131	2,533,876
Current liabilities:
Accounts payable	24,021	17,921
Accrued compensation	29,322	49,178
Accrued liabilities	104,745	140,101
Income taxes payable	24,732	6,249
Current portion of deferred contract revenue	96,252	90,577
Other current liabilities	8,903	7,535
Total current liabilities	287,975	311,561
Long-term deferred contract revenue	254,398	287,768
Liability related to sale of future royalties, net	510,174	0
Long-term lease liabilities	175,020	178,941
Long-term obligations	16,436	15,973
Total liabilities	2,542,830	1,960,989
Stockholders' equity:
Common stock, $0.001 par value; 300,000,000 shares authorized, 143,167,414 and 142,057,736 shares issued and outstanding at June 30, 2023 (unaudited) and December 31, 2022, respectivel	143	142
Additional paid-in capital	2,118,309	2,059,850
Accumulated other comprehensive loss	(50,913)	(57,480)
Accumulated deficit	(1,639,238)	(1,429,625)
Total stockholders' equity	428,301	572,887
Total liabilities and stockholders' equity	2,971,131	2,533,876
1.75 Percent Convertible Senior Notes [Member]
Current liabilities:
Convertible senior notes, net	560,937	0
0 Percent Convertible Senior Notes [Member]
Current liabilities:
Convertible senior notes, net	623,809	622,242
0.125 Percent Convertible Senior Notes [Member]
Current liabilities:
Convertible senior notes, net	$ 114,081	$ 544,504

CONDENSED CONSOLIDATED BALANC_2

CONDENSED CONSOLIDATED BALANCE SHEETS (Parenthetical) - $ / shares	Jun. 30, 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)	143,167,414	142,057,736
Common stock, shares outstanding (in shares)	143,167,414	142,057,736
1.75 Percent Convertible Senior Notes [Member]
LIABILITIES AND STOCKHOLDERS' EQUITY
Interest rate on convertible senior notes	1.75%
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		6 Months Ended
	Jun. 30, 2023	Jun. 30, 2022	Jun. 30, 2023	Jun. 30, 2022
Revenue:
Revenue	$ 188,411	$ 133,791	$ 318,935	$ 275,710
Expenses:
Cost of sales	2,537	4,745	3,880	8,914
Research, development and patent	229,927	180,758	427,740	341,884
Selling, general and administrative	46,142	33,802	91,658	67,929
Total operating expenses	278,606	219,305	523,278	418,727
Loss from operations	(90,195)	(85,514)	(204,343)	(143,017)
Other income (expense):
Investment income	20,792	3,403	39,419	5,396
Interest expense	(2,291)	(2,130)	(3,899)	(4,252)
Interest expense related to sale of future royalties	(17,655)	0	(33,170)	0
Gain (loss) on investments	718	(6,337)	189	(12,963)
Other income (expense)	11,183	(12,297)	11,414	(12,110)
Loss before income tax expense	(77,448)	(102,875)	(190,390)	(166,946)
Income tax expense	(7,842)	(2,260)	(19,223)	(3,354)
Net loss	$ (85,290)	$ (105,135)	$ (209,613)	$ (170,300)
Basic net loss per share (in dollars per share)	$ (0.6)	$ (0.74)	$ (1.47)	$ (1.2)
Diluted net loss per share (in dollars per share)	$ (0.6)	$ (0.74)	$ (1.47)	$ (1.2)
Shares used in computing basic net loss per share (in shares)	143,098	141,794	142,918	141,697
Shares used in computing diluted net loss per share (in shares)	143,098	141,794	142,918	141,697
Commercial Revenue [Member]
Revenue:
Revenue	$ 77,897	$ 78,184	$ 145,664	$ 150,468
SPINRAZA Royalties [Member]
Revenue:
Revenue	61,012	59,627	111,258	113,444
Other Commercial Revenue [Member]
Revenue:
Revenue	16,885	18,557	34,406	37,024
Research and Development Revenue [Member]
Revenue:
Revenue	110,514	55,607	173,271	125,242
Collaborative Agreement Revenue [Member]
Revenue:
Revenue	91,013	38,247	129,347	88,032
Eplontersen Joint Development Revenue [Member]
Revenue:
Revenue	$ 19,501	$ 17,360	$ 43,924	$ 37,210

CONDENSED CONSOLIDATED STATEM_2

CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS - USD ($) $ in Thousands	3 Months Ended		6 Months Ended
	Jun. 30, 2023	Jun. 30, 2022	Jun. 30, 2023	Jun. 30, 2022
CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS [Abstract]
Net loss	$ (85,290)	$ (105,135)	$ (209,613)	$ (170,300)
Unrealized gains (losses) on debt securities, net of tax	(2,000)	(5,018)	6,393	(20,774)
Currency translation adjustment	70	(411)	174	(565)
Comprehensive loss	$ (87,220)	$ (110,564)	$ (203,046)	$ (191,639)

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	(170,300)	(170,300)
Change in unrealized gains (losses), net of tax	0	0	(20,774)	0	(20,774)
Foreign currency translation	0	0	(565)	0	(565)
Issuance of common stock in connection with employee stock plans	$ 1	3,461	0	0	3,462
Issuance of common stock in connection with employee stock plans (in shares)	935
Stock-based compensation expense	$ 0	50,738	0	0	50,738
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options	$ 0	(9,572)	0	0	(9,572)
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options (in shares)	(314)
Balance at Jun. 30, 2022	$ 142	2,008,794	(54,007)	(1,330,203)	624,726
Balance (in shares) at Jun. 30, 2022	141,831
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
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Net loss	$ 0	0	0	(105,135)	(105,135)
Change in unrealized gains (losses), net of tax	0	0	(5,018)	0	(5,018)
Foreign currency translation	0	0	(411)	0	(411)
Issuance of common stock in connection with employee stock plans	$ 0	1,614	0	0	1,614
Issuance of common stock in connection with employee stock plans (in shares)	87
Stock-based compensation expense	$ 0	24,502	0	0	24,502
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options	$ 0	(400)	0	0	(400)
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options (in shares)	(9)
Balance at Jun. 30, 2022	$ 142	2,008,794	(54,007)	(1,330,203)	624,726
Balance (in shares) at Jun. 30, 2022	141,831
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	(209,613)	(209,613)
Change in unrealized gains (losses), net of tax	0	0	6,393	0	6,393
Foreign currency translation	0	0	174	0	174
Issuance of common stock in connection with employee stock plans	$ 1	4,949	0	0	4,950
Issuance of common stock in connection with employee stock plans (in shares)	1,109
Stock-based compensation expense	$ 0	53,510	0	0	53,510
Balance at Jun. 30, 2023	$ 143	2,118,309	(50,913)	(1,639,238)	428,301
Balance (in shares) at Jun. 30, 2023	143,167
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
Increase (Decrease) in Stockholders' Equity [Roll Forward]
Net loss	$ 0	0	0	(85,290)	(85,290)
Change in unrealized gains (losses), net of tax	0	0	(2,000)	0	(2,000)
Foreign currency translation	0	0	70	0	70
Issuance of common stock in connection with employee stock plans	$ 0	2,390	0	0	2,390
Issuance of common stock in connection with employee stock plans (in shares)	144
Stock-based compensation expense	$ 0	26,561	0	0	26,561
Balance at Jun. 30, 2023	$ 143	$ 2,118,309	$ (50,913)	$ (1,639,238)	$ 428,301
Balance (in shares) at Jun. 30, 2023	143,167

CONDENSED CONSOLIDATED STATEM_4

CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS - USD ($) $ in Thousands	6 Months Ended
	Jun. 30, 2023	Jun. 30, 2022
Operating activities:
Net loss	$ (209,613)	$ (170,300)
Adjustments to reconcile net loss to net cash used in operating activities:
Depreciation	5,225	7,484
Amortization of right-of-use operating lease assets	4,826	1,300
Amortization of other assets	1,244	1,197
Amortization of premium (discount) on investments, net	(12,481)	7,867
Amortization of debt issuance costs	2,966	2,688
Non-cash royalty revenue related to sale of royalties	(12,562)	0
Non-cash interest related to sale of future royalties	32,915	0
Stock-based compensation expense	53,510	50,738
Loss (gain) on investments	(301)	54
Gain on early retirement of debt	(11,292)	0
Non-cash losses related to disposal of property, plant and equipment	205	527
Non-cash losses related to other assets	570	951
Changes in operating assets and liabilities:
Contracts receivable	(2,254)	55,145
Inventories	(3,505)	4,995
Other current and long-term assets	(19,696)	(39)
Income taxes payable	18,483	(22)
Accounts payable	5,517	(2,672)
Accrued compensation	(19,856)	(13,825)
Accrued liabilities and other current liabilities	(37,562)	45,170
Deferred contract revenue	(27,695)	(41,004)
Net cash used in operating activities	(231,356)	(49,746)
Investing activities:
Purchases of short-term investments	(932,362)	(663,195)
Proceeds from sale of short-term investments	701,034	380,375
Purchases of property, plant and equipment	(22,483)	(6,040)
Acquisition of licenses and other assets, net	(2,314)	(1,993)
Net cash used in investing activities	(256,125)	(290,853)
Financing activities:
Proceeds from equity, net	4,950	3,462
Payments of tax withholdings related to vesting of employee stock awards and exercise of employee stock options	0	(9,572)
Proceeds from issuance of 1.75 percent convertible senior notes	575,000	0
1.75 percent convertible senior notes issuance costs	(13,658)	0
Repurchase of $434.1 million principal amount of 0.125 percent convertible senior notes	(420,158)	0
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	(75)	0
Net cash provided by (used in) financing activities	635,625	(6,110)
Effects of exchange rates on cash	174	(565)
Net increase (decrease) in cash and cash equivalents	148,318	(347,274)
Cash and cash equivalents at beginning of period	276,472	869,191
Cash and cash equivalents at end of period	424,790	521,917
Supplemental disclosures of cash flow information:
Interest paid	529	1,544
Income taxes paid	510	2
Supplemental disclosures of non-cash investing and financing activities:
Amounts accrued for capital and patent expenditures	$ 251	$ 1,121

CONDENSED CONSOLIDATED STATEM_5

CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS (Parenthetical) - USD ($) $ in Millions	Jun. 30, 2023	Dec. 31, 2022	Jun. 30, 2022
1.75 Percent Convertible Senior Notes [Member]
Financing activities:
Interest rate on convertible senior notes	1.75%
0.125 Percent Convertible Senior Notes [Member]
Financing activities:
Interest rate on convertible senior notes	0.125%	0.125%	0.125%
Principal amount repurchased	$ 434.1

Organization and Basis of Prese

Organization and Basis of Presentation	6 Months Ended
	Jun. 30, 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 and six months ended June 30, 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	6 Months Ended
	Jun. 30, 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 11, Liability Related to Sale of Future Royalties Under our agreement with Royalty Pharma, 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 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. We calculate the liability related to the sale of future royalties, effective interest rate and the related interest expense 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	6 Months Ended
	Jun. 30, 2023
Supplemental Financial Data [Abstract]
Supplemental Financial Data [Text Block]	3. Supplemental Financial Data Inventories Our inventory consisted of the following (in thousands): June 30, 2023 December 31, 2022 Raw materials: Raw materials - clinical $ 17,665 $ 17,061 Raw materials - commercial 5,585 2,699 Total raw materials 23,250 19,760 Work in process 2,092 2,109 Finished goods 196 164 Total inventory $ 25,538 $ 22,033 Accrued Liabilities Our accrued liabilities consisted of the following (in thousands): June 30, 2023 December 31, 2022 Clinical development expenses $ 83,524 $ 116,460 In-licensing expenses 7,179 7,945 Commercial expenses 3,151 3,498 Other miscellaneous expenses 10,891 12,198 Total accrued liabilities $ 104,745 $ 140,101

Revenues

Revenues	6 Months Ended
	Jun. 30, 2023
Revenues [Abstract]
Revenues	4. Revenues During the three and six months ended June 30, 2023 and 2022, our revenues were comprised of the following (in thousands): Three Months Ended June 30, Six Months Ended June 30, 2023 2022 2023 2022 Revenue: Commercial revenue: SPINRAZA royalties $ 61,012 $ 59,627 $ 111,258 $ 113,444 Other commercial revenue: TEGSEDI and WAYLIVRA revenue, net 10,655 10,386 17,133 16,547 Licensing and other royalty revenue 6,230 8,171 17,273 20,477 Total other commercial revenue 16,885 18,557 34,406 37,024 Total commercial revenue 77,897 78,184 145,664 150,468 Research and development revenue: Collaborative agreement revenue 91,013 38,247 129,347 88,032 Eplontersen joint development revenue 19,501 17,360 43,924 37,210 Total research and development revenue 110,514 55,607 173,271 125,242 Total revenue $ 188,411 $ 133,791 $ 318,935 $ 275,710 Refer to Note 5, Collaborative Arrangements and Licensing Agreements

Collaborative Arrangements and

Collaborative Arrangements and Licensing Agreements	6 Months Ended
	Jun. 30, 2023
Collaborative Arrangements and Licensing Agreements [Abstract]
Collaborative Arrangements and Licensing Agreements	5. Collaborative Arrangements and Licensing Agreements Below, we have included our AstraZeneca, Biogen and GSK collaborations, which are our only collaborations with substantive changes during 2023 from those included in Part IV, Item 15, Note 7, Collaborative Arrangements and Licensing Agreements , of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2022. AstraZeneca We have collaborations with AstraZeneca, focused on the joint development and commercialization of eplontersen for the treatment of transthyretin amyloidosis, or ATTR, and focused on the treatment of cardiovascular, renal and metabolic diseases. From inception through , we have received nearly $ million from these collaborations. We are jointly developing and preparing to commercialize eplontersen with AstraZeneca in the U.S. In addition, we granted AstraZeneca exclusive rights to commercialize eplontersen outside the U.S. In the second quarter of 2023, we earned a $ million license fee payment when we licensed rights to Latin America for eplontersen to AstraZeneca. We recognized the upfront payment in full in the second quarter of 2023 because AstraZeneca had full use of the license without any continuing involvement from us. Under our collaboration for cardiovascular, renal and metabolic diseases, AstraZeneca has licensed multiple medicines from us. AstraZeneca is responsible for global development, regulatory and commercialization activities and costs for each of the medicines it has licensed from us. In the second quarter of 2023, . During the three and six months ended June 30, 2023 and 2022, we earned the following revenue from our relationship with AstraZeneca (in thousands, except percentages): Three Months Ended June 30, Six Months Ended June 30, 2023 2022 2023 2022 Revenue from our relationship with AstraZeneca $ 59,501 $ 17,768 $ 83,926 $ 37,611 Percentage of total revenue 32 % 13 % 26 % 14 % We did not have any deferred revenue from our relationship with AstraZeneca at June 30, 2023 or 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. Under our collaborations, we and Biogen are currently developing numerous investigational medicines to treat neurodegenerative diseases in addition to SMA and SOD1-ALS, including medicines in development to treat people with , 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 second quarter of 2023, we earned a $16 million milestone payment from Biogen when the FDA approved Biogen’s New Drug Application, or NDA, for QALSODY. We recognized this milestone payment as R&D revenue in full in the second quarter of 2023 because we did not have any remaining performance obligations related to the milestone payment. Under our collaboration agreement with Biogen, we are eligible to receive tiered royalties ranging from 11 percent to 15 percent on sales of QALSODY. Following the NDA approval in April 2023, we began earning royalties from QALSODY sales, which we recognize as other commercial revenue in our condensed consolidated statements of operations. We will achieve the next milestone payment for QALSODY of $20 million if the European Medicines Agency approves Biogen’s Marketing Authorization Application filing of QALSODY. During the three and six months ended June 30, 2023 and 2022, we earned the following revenue from our relationship with Biogen (in thousands, except percentages): Three Months Ended June 30, Six Months Ended June 30, 2023 2022 2023 2022 Revenue from our relationship with Biogen $ 97,402 $ 76,887 $ 167,903 $ 170,754 Percentage of total revenue 52 % 58 % 53 % 62 % Our condensed consolidated balance sheets at June 30, 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 and six months ended June 30, 2023 and 2022, we earned the following revenue from our relationship with GSK (in thousands, except percentages): Three Months Ended June 30, Six Months Ended June 30, 2023 2022 2023 2022 Revenue from our relationship with GSK $ — $ — $ 15,000 $ — Percentage of total revenue 0 % 0 % 5 % 0 % We did not have any deferred revenue from our relationship with GSK at June 30, 2023 or December 31, 2022.

Basic and Diluted Net Loss Per

Basic and Diluted Net Loss Per Share	6 Months Ended
	Jun. 30, 2023
Basic and Diluted Net Loss Per Share [Abstract]
Basic and Diluted Net Loss Per Share	6. Basic and Diluted Net Loss Per Share Basic net loss per share We calculated our basic net loss per share for the three and six months ended June 30, 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 and six months ended June 30, 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: ● 1.75 percent convertible senior notes, or 1.75% Notes; ● 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 June 30, 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	6 Months Ended
	Jun. 30, 2023
Investments [Abstract]
Investments	7. Investments The following table summarizes the contract maturity of the available-for-sale securities we held as of June 30, 2023: One year 77 % After one year two years 16 % After two years three and a half years 7 % Total 100 % As illustrated above, at June 30, 2023, 93 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 debt securities At June 30, 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 June 30, 2023 Cost Gains Losses Fair Value Available-for-sale debt securities: Corporate debt securities (1) $ 605,532 $ 25 $ (4,763 ) $ 600,794 Debt securities issued by U.S. government agencies 281,703 4 (1,314 ) 280,393 Debt securities issued by the U.S. Treasury (1) 622,829 6 (5,031 ) 617,804 Debt securities issued by states of the U.S. and political subdivisions of the states 42,230 — (269 ) 41,961 Total debt securities with a maturity of one year or less 1,552,294 35 (11,377 ) 1,540,952 Corporate debt securities 220,569 133 (5,135 ) 215,567 Debt securities issued by U.S. government agencies 39,443 — (870 ) 38,573 Debt securities issued by the U.S. Treasury 194,967 — (3,659 ) 191,308 Debt securities issued by states of the U.S. and political subdivisions of the states 12,000 66 (235 ) 11,831 Total debt securities with a maturity of more than one year 466,979 199 (9,899 ) 457,279 Total available-for-sale debt securities $ 2,019,273 $ 234 $ (21,276 ) $ 1,998,231 Equity securities: Publicly traded equity securities included in other current assets (2) $ 11,897 $ 253 $ (3,928 ) $ 8,222 Privately held equity securities included in deposits and other assets (3) 23,115 25,001 (5,125 ) 42,991 Total equity securities 35,012 25,254 (9,053 ) 51,213 Total available-for-sale debt and equity securities $ 2,054,285 $ 25,488 $ (30,329 ) $ 2,049,444 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 six months ended June 30, 2023, we recognized a $2.3 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 , 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 June 30, 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 406 $ 512,975 $ (2,381 ) $ 238,238 $ (7,517 ) $ 751,213 $ (9,898 ) Debt securities issued by U.S. government agencies 86 265,446 (1,208 ) 36,037 (976 ) 301,483 (2,184 ) Debt securities issued by the U.S. Treasury 70 674,046 (6,202 ) 103,565 (2,488 ) 777,611 (8,690 ) Debt securities issued by states of the U.S. and political subdivisions of the states 130 25,394 (183 ) 22,593 (321 ) 47,987 (504 ) Total temporarily impaired securities 692 $ 1,477,861 $ (9,974 ) $ 400,433 $ (11,302 ) $ 1,878,294 $ (21,276 ) 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 intend to hold these securities to maturity and anticipate full recovery of our debt securities’ amortized cost basis at maturity.

Fair Value Measurements

Fair Value Measurements	6 Months Ended
	Jun. 30, 2023
Fair Value Measurements [Abstract]
Fair Value Measurements	8. Fair Value Measurements The following tables present the major security types we held at June 30, 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 June 30, 2023 Quoted Prices in Active Markets (Level 1) Significant Other Observable Inputs (Level 2) Cash equivalents (1) $ 316,359 $ 316,359 $ — Corporate debt securities (2) 816,361 — 816,361 Debt securities issued by U.S. government agencies (3) 318,966 — 318,966 Debt securities issued by the U.S. Treasury (4) 809,112 809,112 — Debt securities issued by states of the U.S. and political subdivisions of the states (4) 53,792 — 53,792 Publicly traded equity securities included in other current assets (5) 8,222 8,222 — Total $ 2,322,812 $ 1,133,693 $ 1,189,119 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 (6) 726,950 — 726,950 Debt securities issued by U.S. government agencies (4) 165,055 — 165,055 Debt securities issued by the U.S. Treasury (4) 748,475 748,475 — Debt securities issued by states of the U.S. and political subdivisions of the states (4) 74,917 — 74,917 Other municipal debt securities (4) 5,994 — 5,994 Publicly traded equity securities included in other current assets (5) 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) $33.7 million was included in cash and cash equivalents, with the difference included in short-term investments, in our condensed consolidated balance sheets. (3) $4.0 million was included in cash and cash equivalents, with the difference included in short-term investments, in our condensed consolidated balance sheets. (4) Included in short-term investments in our condensed consolidated balance sheets. (5) Included in other current assets in our condensed consolidated balance sheets. (6) $11.0 million was included in cash and cash equivalents, with the difference included in short-term investments, in our condensed consolidated balance sheets. Convertible Notes Our 1.75% Notes, 0% Notes and 0.125% Notes had a fair value of $576.3 million, $599.8 million and $107.5 million at June 30, 2023, respectively. Our 0% Notes and 0.125% Notes had a fair value of $587.3 million and $498.9 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	6 Months Ended
	Jun. 30, 2023
Stock-based Compensation Expense [Abstract]
Stock-based Compensation Expense	9. 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, 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 six months ended June 30, 2023 and 2022, we used the following weighted-average assumptions in our Black-Scholes calculations: Employee Stock Options: Six Months Ended June 30, 2023 2022 Risk-free interest rate 3.6 % 1.8 % Dividend yield 0.0 % 0.0 % Volatility 47.3 % 55.1 % Expected life 6.3 years 6.3 years ESPP: Six Months Ended June 30, 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 six months ended June 30, 2023 and 2022 was $39.50 and $34.38 per share, respectively. 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 six months ended June 30, 2023 and 2022 were $58.99 and $42.28 per share, respectively. The following table summarizes stock-based compensation expense for the three and six months ended June 30, 2023 and 2022 (in thousands): Three Months Ended June 30, Six Months Ended June 30, 2023 2022 2023 2022 Cost of sales $ 118 $ 53 $ 237 $ 213 Research, development and patent expense 19,249 18,500 38,816 37,582 Selling, general and administrative expense 7,194 5,949 14,457 12,943 Total stock-based compensation expense $ 26,561 $ 24,502 $ 53,510 $ 50,738 As of June 30, 2023, total unrecognized estimated stock-based compensation expense related to non-vested stock options, RSUs and PRSUs was $50.5 million, $70.7 million and $8.4 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 1.3 years, 1.6 years and 1.9 years, respectively.

Income Taxes

Income Taxes	6 Months Ended
	Jun. 30, 2023
Income Taxes [Abstract]
Income Taxes	10. 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. The resulting tax liability is partially offset by the utilization of our R&D tax credits. We recorded income tax expense of $7.8 million and $19.2 million for the three and six months ended June 30, 2023, respectively, compared to $2.3 million and $3.4 million for the same periods in 2022, respectively. The increase in income tax expense for the three months and six months ended June 30, 2023, compared to the same periods in 2022, relates primarily to the impact of the Royalty Pharma transaction. We continue to maintain a full valuation allowance on all our net deferred tax assets.

Liability Related to Sale of Fu

Liability Related to Sale of Future Royalties	6 Months Ended
	Jun. 30, 2023
Liability Related to Sale of Future Royalties [Abstract]
Liability Related to Sale of Future Royalties	11. 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 determine the effective interest rate used to record interest expense under this agreement based on an estimate of future royalty payments to Royalty Pharma. As of June 30, 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 six months ended June 30, 2023 (in thousands): Proceeds from sale of future royalties $ 500,000 Royalty payments to Royalty Pharma (12,562 ) Interest expense related to sale of future royalties 32,915 Liability related to sale of future royalties as of June 30, 2023 520,353 Issuance costs related to sale of future royalties (10,434 ) Amortization of issuance costs related to sale of future royalties as of June 30, 2023 255 Net liability related to sale of future royalties as of June 30, 2023 $ 510,174 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	6 Months Ended
	Jun. 30, 2023
Convertible Debt [Abstract]
Convertible Debt	12. Convertible Debt 1.75 Percent Convertible Senior Notes In June 2023, we completed a $575.0 million offering of convertible senior notes. We used $420.4 million of the net proceeds from the issuance of the 1.75% Notes to repurchase $434.1 million in principal of our 0.125% Notes. We expect to use the residual net proceeds to settle the 0.125% Notes that remain outstanding. At June 30, 2023, we had the following 1.75% Notes outstanding (in millions except interest rate and price per share data): 1.75% Notes Outstanding principal balance $ 575.0 Unamortized debt issuance costs $ 14.1 Maturity date June 2028 Interest rate 1.75 percent Effective interest rate 2.3 percent Conversion price per share $ 53.73 Total shares of common stock subject to conversion 10.7 0 Percent Convertible Senior Notes and Call Spread In April 2021, we completed a $632.5 million offering of convertible senior notes. We used $257.0 million of the net proceeds from the issuance of the 0% Notes to repurchase $247.9 million in principal of our 1% convertible senior notes, or 1% Notes. At June 30, 2023, we had the following 0% 0% Notes Outstanding principal balance $ 632.5 Unamortized debt issuance costs $ 8.7 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, Organization and Significant Accounting Policies 0.125 Percent Convertible Senior Notes and Call Spread As discussed above, in June 2023, we repurchased $434.1 million of our 0.125% Notes. As a result, the remaining principal balance of our 0.125% Notes was $114.8 million as of June 30, 2023. Additionally, we recorded a $11.3 million gain on the early retirement of debt, which we recorded as other income in our condensed consolidated statements of operations. The gain on the early retirement of our debt is the difference between the amount paid to repurchase our 0.125% Notes and the net carrying balance of the liability at the time that we completed the repurchase. At June 30, 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 $ 114.8 Unamortized debt issuance costs $ 0.7 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 1.4 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 $ 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. Following the repurchase of $ million of our Notes in June 2023, the note hedges and warrants remain outstanding. 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	6 Months Ended
	Jun. 30, 2023
Legal Proceedings [Abstract]
Legal Proceedings	13. 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.

Insider Trading Arrangements

Insider Trading Arrangements	6 Months Ended
	Jun. 30, 2023 shares
Trading Arrangements, by Individual
Material Terms of Trading Arrangement	During the quarter ended June 30, 2023, our Section 16 officers and directors adopted or terminated contracts, instructions or written plans for the purchase or sale of our securities as noted in the table below. Action Date Trading Arrangement Total Shares to Be Sold Expiration Date Rule 10b5-1* Non-Rule 10b5-1** Allene Diaz, Board Member Adoption May 3, 2023 X 1,866 Upon the execution of all instructions provided in the plan C. Frank Bennett, EVP, Chief Scientific Officer Adoption June 29, 2023 X 49,685 Upon the execution of all instructions provided in the plan Eric Swayze, EVP, Research Termination June 28, 2023 X 49,730 Upon the execution of all instructions provided in the plan * Contract, instruction or written plan intended to satisfy the affirmative defense conditions of Rule 10b5-1(c) under the Exchange Act. ** “Non-Rule 10b5-1 trading arrangement” as defined in item 408(c) of Regulation S-K under the Exchange Act.
Allene Diaz [Member]
Trading Arrangements, by Individual
Name	Allene Diaz
Title	Board Member
Rule 10b5-1 Arrangement Adopted	true
Non-Rule 10b5-1 Arrangement Adopted	false
Adoption Date	May 3, 2023
Arrangement Duration
Aggregate Available	1,866
C. Frank Bennett [Member]
Trading Arrangements, by Individual
Name	C. Frank Bennett
Title	EVP, Chief Scientific Officer
Rule 10b5-1 Arrangement Adopted	true
Non-Rule 10b5-1 Arrangement Adopted	false
Adoption Date	June 29, 2023
Arrangement Duration
Aggregate Available	49,685
Eric Swayze [Member]
Trading Arrangements, by Individual
Name	Eric Swayze
Title	EVP, Research
Rule 10b5-1 Arrangement Terminated	true
Non-Rule 10b5-1 Arrangement Terminated	false
Termination Date	June 28, 2023
Arrangement Duration
Aggregate Available	49,730

Organization and Basis of Pre_2

Organization and Basis of Presentation (Policies)	6 Months Ended
	Jun. 30, 2023
Organization and Basis of Presentation [Abstract]
Basis of Presentation	We prepared the unaudited interim condensed consolidated financial statements for the three and six months ended June 30, 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)	6 Months Ended
	Jun. 30, 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 11, Liability Related to Sale of Future Royalties Under our agreement with Royalty Pharma, 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 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. We calculate the liability related to the sale of future royalties, effective interest rate and the related interest expense 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)	6 Months Ended
	Jun. 30, 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 and six months ended June 30, 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 and six months ended June 30, 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: ● 1.75 percent convertible senior notes, or 1.75% Notes; ● 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 June 30, 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)	6 Months Ended
	Jun. 30, 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, 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)	6 Months Ended
	Jun. 30, 2023
Supplemental Financial Data [Abstract]
Inventories	Inventories Our inventory consisted of the following (in thousands): June 30, 2023 December 31, 2022 Raw materials: Raw materials - clinical $ 17,665 $ 17,061 Raw materials - commercial 5,585 2,699 Total raw materials 23,250 19,760 Work in process 2,092 2,109 Finished goods 196 164 Total inventory $ 25,538 $ 22,033
Accrued Liabilities	Accrued Liabilities Our accrued liabilities consisted of the following (in thousands): June 30, 2023 December 31, 2022 Clinical development expenses $ 83,524 $ 116,460 In-licensing expenses 7,179 7,945 Commercial expenses 3,151 3,498 Other miscellaneous expenses 10,891 12,198 Total accrued liabilities $ 104,745 $ 140,101

Revenues (Tables)

Revenues (Tables)	6 Months Ended
	Jun. 30, 2023
Revenues [Abstract]
Revenues	During the three and six months ended June 30, 2023 and 2022, our revenues were comprised of the following (in thousands): Three Months Ended June 30, Six Months Ended June 30, 2023 2022 2023 2022 Revenue: Commercial revenue: SPINRAZA royalties $ 61,012 $ 59,627 $ 111,258 $ 113,444 Other commercial revenue: TEGSEDI and WAYLIVRA revenue, net 10,655 10,386 17,133 16,547 Licensing and other royalty revenue 6,230 8,171 17,273 20,477 Total other commercial revenue 16,885 18,557 34,406 37,024 Total commercial revenue 77,897 78,184 145,664 150,468 Research and development revenue: Collaborative agreement revenue 91,013 38,247 129,347 88,032 Eplontersen joint development revenue 19,501 17,360 43,924 37,210 Total research and development revenue 110,514 55,607 173,271 125,242 Total revenue $ 188,411 $ 133,791 $ 318,935 $ 275,710

Collaborative Arrangements an_2

Collaborative Arrangements and Licensing Agreements (Tables)	6 Months Ended
	Jun. 30, 2023
AstraZeneca [Member]
Collaborative Arrangements and Licensing Agreements [Abstract]
Revenue from Collaborative Relationship	During the three and six months ended June 30, 2023 and 2022, we earned the following revenue from our relationship with AstraZeneca (in thousands, except percentages): Three Months Ended June 30, Six Months Ended June 30, 2023 2022 2023 2022 Revenue from our relationship with AstraZeneca $ 59,501 $ 17,768 $ 83,926 $ 37,611 Percentage of total revenue 32 % 13 % 26 % 14 %
Biogen [Member]
Collaborative Arrangements and Licensing Agreements [Abstract]
Revenue from Collaborative Relationship	During the three and six months ended June 30, 2023 and 2022, we earned the following revenue from our relationship with Biogen (in thousands, except percentages): Three Months Ended June 30, Six Months Ended June 30, 2023 2022 2023 2022 Revenue from our relationship with Biogen $ 97,402 $ 76,887 $ 167,903 $ 170,754 Percentage of total revenue 52 % 58 % 53 % 62 %
GSK [Member]
Collaborative Arrangements and Licensing Agreements [Abstract]
Revenue from Collaborative Relationship	During the three and six months ended June 30, 2023 and 2022, we earned the following revenue from our relationship with GSK (in thousands, except percentages): Three Months Ended June 30, Six Months Ended June 30, 2023 2022 2023 2022 Revenue from our relationship with GSK $ — $ — $ 15,000 $ — Percentage of total revenue 0 % 0 % 5 % 0 %

Investments (Tables)

Investments (Tables)	6 Months Ended
	Jun. 30, 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 June 30, 2023: One year 77 % After one year two years 16 % After two years three and a half years 7 % Total 100 %
Summary of Investments	The following is a summary of our investments (in thousands): Amortized Gross Unrealized Estimated June 30, 2023 Cost Gains Losses Fair Value Available-for-sale debt securities: Corporate debt securities (1) $ 605,532 $ 25 $ (4,763 ) $ 600,794 Debt securities issued by U.S. government agencies 281,703 4 (1,314 ) 280,393 Debt securities issued by the U.S. Treasury (1) 622,829 6 (5,031 ) 617,804 Debt securities issued by states of the U.S. and political subdivisions of the states 42,230 — (269 ) 41,961 Total debt securities with a maturity of one year or less 1,552,294 35 (11,377 ) 1,540,952 Corporate debt securities 220,569 133 (5,135 ) 215,567 Debt securities issued by U.S. government agencies 39,443 — (870 ) 38,573 Debt securities issued by the U.S. Treasury 194,967 — (3,659 ) 191,308 Debt securities issued by states of the U.S. and political subdivisions of the states 12,000 66 (235 ) 11,831 Total debt securities with a maturity of more than one year 466,979 199 (9,899 ) 457,279 Total available-for-sale debt securities $ 2,019,273 $ 234 $ (21,276 ) $ 1,998,231 Equity securities: Publicly traded equity securities included in other current assets (2) $ 11,897 $ 253 $ (3,928 ) $ 8,222 Privately held equity securities included in deposits and other assets (3) 23,115 25,001 (5,125 ) 42,991 Total equity securities 35,012 25,254 (9,053 ) 51,213 Total available-for-sale debt and equity securities $ 2,054,285 $ 25,488 $ (30,329 ) $ 2,049,444 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 six months ended June 30, 2023, we recognized a $2.3 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 , 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 June 30, 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 406 $ 512,975 $ (2,381 ) $ 238,238 $ (7,517 ) $ 751,213 $ (9,898 ) Debt securities issued by U.S. government agencies 86 265,446 (1,208 ) 36,037 (976 ) 301,483 (2,184 ) Debt securities issued by the U.S. Treasury 70 674,046 (6,202 ) 103,565 (2,488 ) 777,611 (8,690 ) Debt securities issued by states of the U.S. and political subdivisions of the states 130 25,394 (183 ) 22,593 (321 ) 47,987 (504 ) Total temporarily impaired securities 692 $ 1,477,861 $ (9,974 ) $ 400,433 $ (11,302 ) $ 1,878,294 $ (21,276 )

Fair Value Measurements (Tables

Fair Value Measurements (Tables)	6 Months Ended
	Jun. 30, 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 June 30, 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 June 30, 2023 Quoted Prices in Active Markets (Level 1) Significant Other Observable Inputs (Level 2) Cash equivalents (1) $ 316,359 $ 316,359 $ — Corporate debt securities (2) 816,361 — 816,361 Debt securities issued by U.S. government agencies (3) 318,966 — 318,966 Debt securities issued by the U.S. Treasury (4) 809,112 809,112 — Debt securities issued by states of the U.S. and political subdivisions of the states (4) 53,792 — 53,792 Publicly traded equity securities included in other current assets (5) 8,222 8,222 — Total $ 2,322,812 $ 1,133,693 $ 1,189,119 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 (6) 726,950 — 726,950 Debt securities issued by U.S. government agencies (4) 165,055 — 165,055 Debt securities issued by the U.S. Treasury (4) 748,475 748,475 — Debt securities issued by states of the U.S. and political subdivisions of the states (4) 74,917 — 74,917 Other municipal debt securities (4) 5,994 — 5,994 Publicly traded equity securities included in other current assets (5) 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) $33.7 million was included in cash and cash equivalents, with the difference included in short-term investments, in our condensed consolidated balance sheets. (3) $4.0 million was included in cash and cash equivalents, with the difference included in short-term investments, in our condensed consolidated balance sheets. (4) Included in short-term investments in our condensed consolidated balance sheets. (5) Included in other current assets in our condensed consolidated balance sheets. (6) $11.0 million was included in cash and cash equivalents, with the difference included in short-term investments, in our condensed consolidated balance sheets.

Stock-based Compensation Expe_3

Stock-based Compensation Expense (Tables)	6 Months Ended
	Jun. 30, 2023
Stock-based Compensation Expense [Abstract]
Weighted-Average Assumptions for Stock Options	Employee Stock Options: Six Months Ended June 30, 2023 2022 Risk-free interest rate 3.6 % 1.8 % Dividend yield 0.0 % 0.0 % Volatility 47.3 % 55.1 % Expected life 6.3 years 6.3 years
Weighted-Average Assumptions for ESPP	ESPP: Six Months Ended June 30, 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 and six months ended June 30, 2023 and 2022 (in thousands): Three Months Ended June 30, Six Months Ended June 30, 2023 2022 2023 2022 Cost of sales $ 118 $ 53 $ 237 $ 213 Research, development and patent expense 19,249 18,500 38,816 37,582 Selling, general and administrative expense 7,194 5,949 14,457 12,943 Total stock-based compensation expense $ 26,561 $ 24,502 $ 53,510 $ 50,738

Liability Related to Sale of _2

Liability Related to Sale of Future Royalties (Tables)	6 Months Ended
	Jun. 30, 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 six months ended June 30, 2023 (in thousands): Proceeds from sale of future royalties $ 500,000 Royalty payments to Royalty Pharma (12,562 ) Interest expense related to sale of future royalties 32,915 Liability related to sale of future royalties as of June 30, 2023 520,353 Issuance costs related to sale of future royalties (10,434 ) Amortization of issuance costs related to sale of future royalties as of June 30, 2023 255 Net liability related to sale of future royalties as of June 30, 2023 $ 510,174

Convertible Debt (Tables)

Convertible Debt (Tables)	6 Months Ended
	Jun. 30, 2023
1.75% Notes [Member]
Convertible Notes [Abstract]
Convertible Senior Notes	At June 30, 2023, we had the following 1.75% Notes outstanding (in millions except interest rate and price per share data): 1.75% Notes Outstanding principal balance $ 575.0 Unamortized debt issuance costs $ 14.1 Maturity date June 2028 Interest rate 1.75 percent Effective interest rate 2.3 percent Conversion price per share $ 53.73 Total shares of common stock subject to conversion 10.7
0% Notes [Member]
Convertible Notes [Abstract]
Convertible Senior Notes	At June 30, 2023, we had the following 0% 0% Notes Outstanding principal balance $ 632.5 Unamortized debt issuance costs $ 8.7 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 June 30, 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 $ 114.8 Unamortized debt issuance costs $ 0.7 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 1.4

Organization and Basis of Pre_3

Organization and Basis of Presentation (Details)	6 Months Ended
	Jun. 30, 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	Jun. 30, 2023	Dec. 31, 2022
Inventory [Abstract]
Raw materials	$ 23,250	$ 19,760
Work in process	2,092	2,109
Finished goods	196	164
Total inventory	25,538	22,033
Clinical [Member]
Inventory [Abstract]
Raw materials	17,665	17,061
Commercial [Member]
Inventory [Abstract]
Raw materials	$ 5,585	$ 2,699

Supplemental Financial Data, Ac

Supplemental Financial Data, Accrued Liabilities (Details) - USD ($) $ in Thousands	Jun. 30, 2023	Dec. 31, 2022
Accrued Liabilities [Abstract]
Clinical development expenses	$ 83,524	$ 116,460
In-licensing expenses	7,179	7,945
Commercial expenses	3,151	3,498
Other miscellaneous expenses	10,891	12,198
Total accrued liabilities	$ 104,745	$ 140,101

Revenues (Details)

Revenues (Details) - USD ($) $ in Thousands	3 Months Ended		6 Months Ended
	Jun. 30, 2023	Jun. 30, 2022	Jun. 30, 2023	Jun. 30, 2022
Revenues [Abstract]
Revenue	$ 188,411	$ 133,791	$ 318,935	$ 275,710
Commercial Revenue [Member]
Revenues [Abstract]
Revenue	77,897	78,184	145,664	150,468
SPINRAZA Royalties [Member]
Revenues [Abstract]
Revenue	61,012	59,627	111,258	113,444
Other Commercial Revenue [Member]
Revenues [Abstract]
Revenue	16,885	18,557	34,406	37,024
TEGSEDI and WAYLIVRA Revenue, Net [Member]
Revenues [Abstract]
Revenue	10,655	10,386	17,133	16,547
Licensing and Other Royalty Revenue [Member]
Revenues [Abstract]
Revenue	6,230	8,171	17,273	20,477
Research and Development Revenue [Member]
Revenues [Abstract]
Revenue	110,514	55,607	173,271	125,242
Collaborative Agreement Revenue [Member]
Revenues [Abstract]
Revenue	91,013	38,247	129,347	88,032
Eplontersen Joint Development Revenue [Member]
Revenues [Abstract]
Revenue	$ 19,501	$ 17,360	$ 43,924	$ 37,210

Collaborative Arrangements an_3

Collaborative Arrangements and Licensing Agreements, AstraZeneca (Details) $ in Thousands	3 Months Ended		6 Months Ended
	Jun. 30, 2023 USD ($) Agreement	Jun. 30, 2022 USD ($)	Jun. 30, 2023 USD ($) Agreement	Jun. 30, 2022 USD ($)	Dec. 31, 2022 USD ($)
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue	$ 188,411	$ 133,791	$ 318,935	$ 275,710
AstraZeneca [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of collaboration agreements | Agreement	2		2
Revenue	$ 59,501	$ 17,768	$ 83,926	$ 37,611
Deferred revenue	$ 0		$ 0		$ 0
AstraZeneca [Member] | Revenue [Member] | Strategic Partner [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Concentration percentage	32%	13%	26%	14%
AstraZeneca [Member] | Maximum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative payments received	$ 610,000		$ 610,000
Eplontersen Collaboration [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of collaboration agreements | Agreement	1		1
Revenue	$ 20,000
Eplontersen Collaboration [Member] | Maximum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Next payment to be achieved	$ 50,000		$ 50,000
Cardiovascular, Renal and Metabolic Diseases Collaboration [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Number of collaboration agreements | Agreement	1		1
Cardiovascular, Renal and Metabolic Diseases Collaboration [Member] | Maximum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Next payment to be achieved	$ 30,000		$ 30,000
Cardiovascular, Renal and Metabolic Diseases Collaboration [Member] | ION839 [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue	$ 20,000

Collaborative Arrangements an_4

Collaborative Arrangements and Licensing Agreements, Biogen (Details) - USD ($) $ in Thousands	3 Months Ended		6 Months Ended
	Jun. 30, 2023	Jun. 30, 2022	Jun. 30, 2023	Jun. 30, 2022	Dec. 31, 2022
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue	$ 188,411	$ 133,791	$ 318,935	$ 275,710
Biogen Collaborations [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue	97,402	$ 76,887	167,903	$ 170,754
Deferred revenue	$ 323,100		$ 323,100		$ 351,200
Biogen Collaborations [Member] | Revenue [Member] | Strategic Partner [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Concentration percentage	52%	58%	53%	62%
Biogen Collaborations [Member] | Minimum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative payments received	$ 3,600,000		$ 3,600,000
2013 Strategic Neurology [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue	16,000
2013 Strategic Neurology [Member] | QALSODY [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Next payment to be achieved	$ 20,000		$ 20,000
2013 Strategic Neurology [Member] | QALSODY [Member] | Minimum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Royalty percentage received on sales of medicine			11%
2013 Strategic Neurology [Member] | QALSODY [Member] | Maximum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Royalty percentage received on sales of medicine			15%

Collaborative Arrangements an_5

Collaborative Arrangements and Licensing Agreements, GSK (Details) - USD ($) $ in Thousands	3 Months Ended			6 Months Ended
	Jun. 30, 2023	Mar. 31, 2023	Jun. 30, 2022	Jun. 30, 2023	Jun. 30, 2022	Dec. 31, 2022
Collaborative Arrangement and Licensing Agreement [Abstract]
Revenue	$ 188,411		$ 133,791	$ 318,935	$ 275,710
GSK [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Next payment to be achieved	15,000			15,000
Revenue	0		$ 0	15,000	$ 0
Deferred revenue	$ 0			$ 0		$ 0
GSK [Member] | Revenue [Member] | Strategic Partner [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Concentration percentage	0%		0%	5%	0%
GSK [Member] | Minimum [Member]
Collaborative Arrangement and Licensing Agreement [Abstract]
Cumulative payments received	$ 105,000			$ 105,000
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)	Jun. 30, 2023	Dec. 31, 2022	Jun. 30, 2022
1.75% Notes [Member]
Diluted Net Loss per Share [Abstract]
Interest rate on convertible senior notes	1.75%
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)	6 Months Ended
	Jun. 30, 2023
Contract Maturity of Available-for-Sale Securities [Abstract]
One year or less	77%
After one year but within two years	16%
After two years but within three and a half years	7%
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	93%

Investments, Summary of Investm

Investments, Summary of Investments (Details) $ in Thousands		6 Months Ended
		Jun. 30, 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		$ 1,552,294	$ 1,223,522
Gross unrealized gains		35	64
Gross unrealized losses		(11,377)	(12,018)
Estimated fair value		1,540,952	1,211,568
Available-for-sale Debt Securities with Maturity of More Than One Year [Abstract]
Amortized cost		466,979	525,314
Gross unrealized gains		199	130
Gross unrealized losses		(9,899)	(15,621)
Estimated fair value		457,279	509,823
Available-for-sale Debt Securities [Abstract]
Amortized cost		2,019,273	1,748,836
Gross unrealized gains		234	194
Gross unrealized losses		(21,276)	(27,639)
Estimated fair value		1,998,231	1,721,391
Equity Securities [Abstract]
Amortized cost		35,012	35,012
Gross unrealized gains		25,254	17,257
Gross unrealized losses		(9,053)	(1,358)
Estimated fair value		51,213	50,911
Available-for-sale Debt and Equity Securities [Abstract]
Amortized cost		2,054,285	1,783,848
Gross unrealized gains		25,488	17,451
Gross unrealized losses		(30,329)	(28,997)
Estimated fair value		2,049,444	1,772,302
Corporate Debt Securities [Member]
Available-for-sale Debt Securities with Maturity of One Year or Less [Abstract]
Amortized cost	[1]	605,532	513,790
Gross unrealized gains		25	23
Gross unrealized losses		(4,763)	(4,365)
Estimated fair value		600,794	509,448
Available-for-sale Debt Securities with Maturity of More Than One Year [Abstract]
Amortized cost		220,569	227,631
Gross unrealized gains		133	14
Gross unrealized losses		(5,135)	(10,143)
Estimated fair value		215,567	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		281,703	133,585
Gross unrealized gains		4	0
Gross unrealized losses		(1,314)	(1,829)
Estimated fair value		280,393	131,756
Available-for-sale Debt Securities with Maturity of More Than One Year [Abstract]
Amortized cost		39,443	34,339
Gross unrealized gains		0	0
Gross unrealized losses		(870)	(1,040)
Estimated fair value		38,573	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]	622,829	512,655
Gross unrealized gains		6	23
Gross unrealized losses		(5,031)	(5,124)
Estimated fair value		617,804	507,554
Available-for-sale Debt Securities with Maturity of More Than One Year [Abstract]
Amortized cost		194,967	245,030
Gross unrealized gains		0	0
Gross unrealized losses		(3,659)	(4,109)
Estimated fair value		191,308	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		42,230	57,484
Gross unrealized gains		0	18
Gross unrealized losses		(269)	(686)
Estimated fair value		41,961	56,816
Available-for-sale Debt Securities with Maturity of More Than One Year [Abstract]
Amortized cost		12,000	18,314
Gross unrealized gains		66	116
Gross unrealized losses		(235)	(329)
Estimated fair value		11,831	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		253	0
Gross unrealized losses		(3,928)	(1,358)
Estimated fair value		8,222	10,539
Available-for-sale Debt and Equity Securities [Abstract]
Unrealized loss on equity securities		(2,300)
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 six months ended June 30, 2023, we recognized a $2.3 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 , 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	Jun. 30, 2023 USD ($) Investment
Temporarily Impaired Investments [Abstract]
Number of investments | Investment	692
Estimated Fair Value [Abstract]
Less than 12 months of temporary impairment	$ 1,477,861
More than 12 months of temporary impairment	400,433
Total temporary impairment	1,878,294
Unrealized Losses [Abstract]
Less than 12 months of temporary impairment	(9,974)
More than 12 months of temporary impairment	(11,302)
Total temporary impairment	$ (21,276)
Corporate Debt Securities [Member]
Temporarily Impaired Investments [Abstract]
Number of investments | Investment	406
Estimated Fair Value [Abstract]
Less than 12 months of temporary impairment	$ 512,975
More than 12 months of temporary impairment	238,238
Total temporary impairment	751,213
Unrealized Losses [Abstract]
Less than 12 months of temporary impairment	(2,381)
More than 12 months of temporary impairment	(7,517)
Total temporary impairment	$ (9,898)
Debt Securities Issued by U.S. Government Agencies [Member]
Temporarily Impaired Investments [Abstract]
Number of investments | Investment	86
Estimated Fair Value [Abstract]
Less than 12 months of temporary impairment	$ 265,446
More than 12 months of temporary impairment	36,037
Total temporary impairment	301,483
Unrealized Losses [Abstract]
Less than 12 months of temporary impairment	(1,208)
More than 12 months of temporary impairment	(976)
Total temporary impairment	$ (2,184)
Debt Securities Issued by the U.S. Treasury [Member]
Temporarily Impaired Investments [Abstract]
Number of investments | Investment	70
Estimated Fair Value [Abstract]
Less than 12 months of temporary impairment	$ 674,046
More than 12 months of temporary impairment	103,565
Total temporary impairment	777,611
Unrealized Losses [Abstract]
Less than 12 months of temporary impairment	(6,202)
More than 12 months of temporary impairment	(2,488)
Total temporary impairment	$ (8,690)
Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member]
Temporarily Impaired Investments [Abstract]
Number of investments | Investment	130
Estimated Fair Value [Abstract]
Less than 12 months of temporary impairment	$ 25,394
More than 12 months of temporary impairment	22,593
Total temporary impairment	47,987
Unrealized Losses [Abstract]
Less than 12 months of temporary impairment	(183)
More than 12 months of temporary impairment	(321)
Total temporary impairment	$ (504)

Fair Value Measurements (Detail

Fair Value Measurements (Details) - USD ($) $ in Thousands		Jun. 30, 2023		Dec. 31, 2022		Jun. 30, 2022
Fair Value Measurements [Abstract]
Available-for-sale securities		$ 1,998,231		$ 1,721,391
Equity securities		$ 51,213		$ 50,911
1.75% Notes [Member]
Fair Value Measurements [Abstract]
Interest rate on convertible senior notes		1.75%
0% Notes [Member]
Fair Value Measurements [Abstract]
Interest rate on convertible senior notes		0%		0%		0%
0.125% Notes [Member]
Fair Value Measurements [Abstract]
Interest rate on convertible senior notes		0.125%		0.125%		0.125%
Publicly Traded Equity Securities [Member]
Fair Value Measurements [Abstract]
Equity securities		$ 8,222		$ 10,539
Recurring Basis [Member]
Fair Value Measurements [Abstract]
Cash equivalents	[1]	316,359		211,655
Total		2,322,812		1,943,585
Recurring Basis [Member] | Corporate Debt Securities [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		816,361	[2]	726,950	[3]
Recurring Basis [Member] | Corporate Debt Securities [Member] | Cash and Cash Equivalents [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		33,700		11,000
Recurring Basis [Member] | Debt Securities Issued by U.S. Government Agencies [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		318,966	[4]	165,055	[5]
Recurring Basis [Member] | Debt Securities Issued by U.S. Government Agencies [Member] | Cash and Cash Equivalents [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		4,000
Recurring Basis [Member] | Debt Securities Issued by the U.S. Treasury [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities	[5]	809,112		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	[5]	53,792		74,917
Recurring Basis [Member] | Other Municipal Debt Securities [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities	[5]			5,994
Recurring Basis [Member] | Publicly Traded Equity Securities [Member] | Other Current Assets [Member]
Fair Value Measurements [Abstract]
Equity securities	[6]	8,222		10,539
Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member]
Fair Value Measurements [Abstract]
Cash equivalents		316,359		211,655
Total		1,133,693		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		809,112		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		8,222		10,539
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member]
Fair Value Measurements [Abstract]
Cash equivalents		0		0
Total		1,189,119		972,916
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | 1.75% Notes [Member]
Fair Value Measurements [Abstract]
Convertible notes		576,300
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | 0% Notes [Member]
Fair Value Measurements [Abstract]
Convertible notes		599,800		587,300
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | 0.125% Notes [Member]
Fair Value Measurements [Abstract]
Convertible notes		107,500		498,900
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Corporate Debt Securities [Member]
Fair Value Measurements [Abstract]
Available-for-sale securities		816,361		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		318,966		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		53,792		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]$33.7 million was included in cash and cash equivalents, with the difference included in short-term investments, in our condensed consolidated balance sheets.[3]$11.0 million was included in cash and cash equivalents, with the difference included in short-term investments, in our condensed consolidated balance sheets.[4]$4.0 million was included in cash and cash equivalents, with the difference included in short-term investments, in our condensed consolidated balance sheets.[5]Included in short-term investments in our condensed consolidated balance sheets.[6]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		6 Months Ended
	Jun. 30, 2023 USD ($)	Jun. 30, 2022 USD ($)	Jun. 30, 2023 USD ($) Period $ / shares shares	Jun. 30, 2022 USD ($) $ / shares
Stock-based Compensation Expense [Abstract]
Stock-based compensation expense	$ 26,561	$ 24,502	$ 53,510	$ 50,738
Cost of Sales [Member]
Stock-based Compensation Expense [Abstract]
Stock-based compensation expense	118	53	237	213
Research, Development and Patent Expense [Member]
Stock-based Compensation Expense [Abstract]
Stock-based compensation expense	19,249	18,500	38,816	37,582
Selling, General and Administrative Expense [Member]
Stock-based Compensation Expense [Abstract]
Stock-based compensation expense	7,194	$ 5,949	14,457	$ 12,943
Stock Options [Member]
Unrecognized Compensation Expense [Abstract]
Unrecognized compensation expense related to non-vested stock options	50,500		$ 50,500
Weighted average period for recognition			1 year 3 months 18 days
Stock Options [Member] | Employees [Member]
Weighted-Average Assumptions [Abstract]
Risk-free interest rate			3.60%	1.80%
Dividend yield			0%	0%
Volatility			47.30%	55.10%
Expected life			6 years 3 months 18 days	6 years 3 months 18 days
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	70,700		$ 70,700
Weighted average period for recognition			1 year 7 months 6 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			$ 39.5	$ 34.38
PRSUs [Member]
Unrecognized Compensation Expense [Abstract]
Unrecognized compensation cost related to non-vested units	$ 8,400		$ 8,400
Weighted average period for recognition			1 year 10 months 24 days
PRSUs [Member] | Section 16 Officers [Member]
RSUs and PRSUs [Abstract]
Weighted-average grant date fair value (in dollars per share) | $ / shares			$ 58.99	$ 42.28
PRSUs [Member] | Granted in 2020 - 2022 [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
PRSUs [Member] | Granted in 2020 - 2022 [Member] | Section 16 Officers [Member] | Minimum [Member]
RSUs and PRSUs [Abstract]
Percentage of units guaranteed to vest			0%
PRSUs [Member] | Granted in 2020 - 2022 [Member] | Section 16 Officers [Member] | Maximum [Member]
RSUs and PRSUs [Abstract]
Percentage of units guaranteed to vest			150%
PRSUs [Member] | Granted in 2020 - 2022 [Member] | Section 16 Officers [Member] | One-Year Period [Member]
RSUs and PRSUs [Abstract]
Vesting percentage			33.30%
Vesting period			1 year
PRSUs [Member] | Granted in 2020 - 2022 [Member] | Section 16 Officers [Member] | Two-Year Period [Member]
RSUs and PRSUs [Abstract]
Vesting percentage			33.30%
Vesting period			2 years
PRSUs [Member] | Granted in 2020 - 2022 [Member] | Section 16 Officers [Member] | Three-Year Period [Member]
RSUs and PRSUs [Abstract]
Vesting percentage			33.30%
Vesting period			3 years
PRSUs [Member] | Granted in 2023 [Member] | Section 16 Officers [Member]
RSUs and PRSUs [Abstract]
Vesting percentage			100%
Vesting period			3 years
Number of units guaranteed to vest (in shares) | shares			0
PRSUs [Member] | Granted in 2023 [Member] | Section 16 Officers [Member] | Minimum [Member]
RSUs and PRSUs [Abstract]
Percentage of units guaranteed to vest			0%
PRSUs [Member] | Granted in 2023 [Member] | Section 16 Officers [Member] | Maximum [Member]
RSUs and PRSUs [Abstract]
Percentage of units guaranteed to vest			200%

Income Taxes (Details)

Income Taxes (Details) - USD ($) $ in Thousands	3 Months Ended		6 Months Ended
	Jun. 30, 2023	Jun. 30, 2022	Jun. 30, 2023	Jun. 30, 2022
Income Taxes [Abstract]
Income tax expense	$ 7,842	$ 2,260	$ 19,223	$ 3,354

Liability Related to Sale of _3

Liability Related to Sale of Future Royalties (Details) - USD ($) $ in Thousands	1 Months Ended	6 Months Ended
	Jan. 31, 2023	Jun. 30, 2023	Jun. 30, 2022
Royalty Revenue Monetization [Abstract]
Transaction costs		$ 10,434	$ 0
Proceeds from sale of future royalties		500,000	0
Royalty payments to Royalty Pharma		(12,562)	0
Interest expense related to sale of future royalties		32,915	0
Issuance costs related to sale of future royalties		(10,434)	$ 0
Net liability related to sale of future royalties		510,174
Royalty Purchase Agreement [Member]
Royalty Revenue Monetization [Abstract]
Upfront payment received	$ 500,000
Maximum amount of payments receivable for additional milestones		625,000
Transaction costs		$ 10,434
Effective interest rate		13.50%
Proceeds from sale of future royalties		$ 500,000
Royalty payments to Royalty Pharma		(12,562)
Interest expense related to sale of future royalties		32,915
Liability related to sale of future royalties as of		520,353
Issuance costs related to sale of future royalties		(10,434)
Amortization of issuance costs related to sale of future royalties		255
Net liability related to sale of future royalties		510,174
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, $ in Thousands, shares in Millions	1 Months Ended			6 Months Ended
	Jun. 30, 2023	Apr. 30, 2021	Dec. 31, 2019	Jun. 30, 2023	Jun. 30, 2022	Dec. 31, 2022
Convertible Debt [Abstract]
Gain on early retirement of debt				$ 11,292	$ 0
1.75% Notes [Member]
Convertible Debt [Abstract]
Face amount of offering	$ 575,000			575,000
Outstanding principal balance	575,000			575,000
Unamortized debt issuance costs	$ 14,100			$ 14,100
Maturity date				Jun. 30, 2028
Interest rate	1.75%			1.75%
Effective interest rate	2.30%			2.30%
Conversion price per share (in dollars per share)	$ 53.73			$ 53.73
Total shares of common stock subject to conversion (in shares)	10.7			10.7
Percentage of principal amount used as purchase price upon occurrence of fundamental change				100%
0% Notes [Member]
Convertible Debt [Abstract]
Face amount of offering		$ 632,500
Outstanding principal balance	$ 632,500			$ 632,500
Unamortized debt issuance costs	$ 8,700			$ 8,700
Maturity date				Apr. 30, 2026
Interest rate	0%			0%	0%	0%
Effective interest rate	0.50%			0.50%
Conversion price per share (in dollars per share)	$ 57.84			$ 57.84
Effective conversion price per share with call spread (in dollars per share)	$ 76.39			$ 76.39
Total shares of common stock subject to conversion (in shares)	10.9			10.9
Cost of call spread		46,900
Purchase of note hedges		136,700
Proceeds from issuance of warrants		89,800
Percentage of principal amount used as purchase price upon occurrence of fundamental change				100%
1% Notes [Member]
Convertible Debt [Abstract]
Repurchase of convertible notes		257,000
Principal amount repurchased		$ 247,900
Interest rate	1%			1%
0.125% Notes [Member]
Convertible Debt [Abstract]
Repurchase of convertible notes	$ 420,400
Principal amount repurchased	434,100			$ 434,100
Outstanding principal balance	114,800			114,800
Unamortized debt issuance costs	$ 700			$ 700
Maturity date				Dec. 31, 2024
Interest rate	0.125%			0.125%	0.125%	0.125%
Effective interest rate	0.50%			0.50%
Conversion price per share (in dollars per share)	$ 83.28			$ 83.28
Effective conversion price per share with call spread (in dollars per share)	$ 123.38			$ 123.38
Total shares of common stock subject to conversion (in shares)	1.4			1.4
Cost of call spread			$ 52,600
Purchase of note hedges			108,700
Proceeds from issuance of warrants			$ 56,100
Percentage of principal amount used as purchase price upon occurrence of fundamental change				100%
0.125% Notes [Member] | Other Income [Member]
Convertible Debt [Abstract]
Gain on early retirement of debt	$ 11,300