Ionis Pharmaceuticals

Biotechnology company

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Ionis Pharmaceuticals, Inc.

Formerly| Isis Pharmaceuticals, Inc.
Company type| Public

Traded as

* Nasdaq: IONS
* Russell 1000 component

Industry| Biotechnology
Founded| 1989; 36 years ago (1989)
Founder| Stanley T. Crooke
Headquarters| Carlsbad, California, U.S.

Key people

| Brett P. Monia (CEO)[1]
Elizabeth L. Hougen (CFO)[2]
Joseph Loscalzo
(chairman of the board)[3]
Products| nusinersen, inotersen, volanesorsen, olezarsen, eplontersen, tofersen
Revenue|  US$705 million (2024)

Net income

|  US$−270 million (2022)
Total assets|  US$3 billion (2024)
Total equity|  US$588 million (2024)

Number of employees

| 1,069 (2024)
Website| ionispharma.com
Footnotes / references
[4][5]

Ionis Pharmaceuticals, Inc. is a biotechnology company based in Carlsbad, California, that specializes in discovering and developing RNA-targeted therapeutics. The company has three commercially approved medicines: Spinraza (Nusinersen), Tegsedi (Inotersen), and Waylivra (Volanesorsen), and has four drugs in pivotal studies: tominersen for Huntington's disease (together with Roche), tofersen for SOD1-ALS, AKCEA-APO(a)-LRx for cardiovascular disease, and AKCEA-TTR-LRx for all forms of TTR amyloidosis.[5]

The company was named Isis Pharmaceuticals until December 2015.[6]

## History

[edit]

The company was founded in 1989 as Isis Pharmaceuticals by Stanley T. Crooke, a former head of research of GlaxoSmithKline, with the goal of commercializing antisense therapy.[7]

In 1992, the company received its first approval by the Food and Drug Administration for an investigational new drug application in 1992 for a genital warts drug candidate. The FDA approval marked the first time for the company to conduct any antisense therapy and to be tested in humans.[8]

In 1995, their oligonucleotide-based drug for genital warts failed in clinical trials and Isis terminated development. By that time, Gilead Sciences had left the field of antisense therapy, leaving only Isis, Hybridon, Genta and Lynx Therapeutics working in the field.[9] Gilead sold its patents, developed around antisense, to Isis.[10]

In December 2015, Isis Pharmaceuticals changed name to Ionis Pharmaceuticals, driven in part by the rise of an international terrorist group, Islamic State of Iraq and the Levant, commonly known as ISIL or ISIS in news media.[6][11]

In 2017, the company completed the corporate spin-off of its rare lipid disorder subsidiary, Akcea Therapeutics.[12]

## Products

[edit]

The company's first marketed drug was fomivirsen (Vitravene, used to treat cytomegalovirus retinitis (CMV) in immunocompromised patients).[13] It was discovered at the NIH and was licensed and initially developed by Isis, which subsequently licensed it to Novartis.[14] It was approved by the FDA for CMV in August 1998 as the first antisense drug.[15] Novartis withdrew the marketing authorization for fomivirsen in the European Union in 2002[16] and in the United States in 2006. The drug was withdrawn because the development of HAART dramatically reduced the number of cases of CMV rinitis.[14]

The antisense field anticipated that the approval of fomivirsen marked the beginning of a new age of antisense drug treatments that would be similar to the uptake of monoclonal antibody therapy, but the next FDA approval of an antisense drug came in 2013.[15] Part of what held up all companies in the field was the way that the oligomers were chemically modified to prevent hydrolysis also reduced affinity to the antisense molecules' targets; by 2004 the field was shifting to second generation modifications.[17] Clinical trials of antisense therapeutics by all the companies in the early 2000s were also plagued by lack of efficacy and immune reactions to drug candidates.[18] Isis cut its workforce by 40% in 2005 due to weak sales of fomivirsen and lack of confidence by the market in antisense technology.[19]

In 2007, Isis and Alnylam Pharmaceuticals, which focuses on RNA interference, formed a 50/50 joint venture, Regulus Therapeutics, to apply their intellectual property and knowledge around oligomer biotherapeutics to micro-RNA targets.[20]

In 2008, Isis and Genzyme entered into a partnered drug candidate mipomersen (Kynamro), intended to treat homozygous familial hypercholesterolemia, and other drug candidates [which?]; the deal included Genzyme buying $150 million of Isis stock and paying a $175 million license fee, as well as milestone fees and royalties.[21] Mipomersen was rejected by the European Medicines Agency in 2012[22] and again in 2013;[23] it was approved by the FDA in 2013.[15] In January 2016, Ionis terminated its arrangement with Genzyme, stating that the drug had been poorly marketed.[24] In May 2016, Ionis licensed the rights to the drug to Kastle Therapeutics for $15 million upfront with another $10 million due in May 2019, up to $70 million in milestones based on sales, and royalties, with Ionis paying 3% royalty and 3% of non-cash royalty it receives to Genzyme.[25] Mipomersen has still not been approved in Europe.[18]

In December 2016, Ionis's drug nusinersen (Spinraza) was approved by the FDA.[26] It had been discovered in a collaboration between Adrian Krainer at Cold Spring Harbor Laboratory and Ionis (then Isis)[27][28][18][29] and preclinical work was done at University of Massachusetts.[30] The drug was initially developed by Ionis, which partnered with Biogen on development starting in 2012; in 2015 Biogen acquired an exclusive license to the drug for a $75 million license fee, milestone payments up to $150M, and tiered royalties between 10 and 15% thereafter; Biogen also paid for all development subsequent to taking the license.[31] The license to Biogen included licenses to intellectual property that Ionis had acquired from Cold Spring Harbor and University of Massachusetts.[32]

As of December 2016, Ionis had ten candidates for various liver diseases in clinical trials and a drug it discovered, alicaforsen, was in a Phase III trial run by another company.[18] It also had a huntingtin gene-lowering antisense molecule for Huntington's disease in clinical trial.[33]

In December 2024, Ionis Pharmaceuticals secured FDA approval for Tryngolza (olezarsen), a treatment for familial chylomicronemia syndrome (FCS), a rare and life-threatening genetic condition that prevents the body from properly breaking down fats.[34][35] This marks a corporate milestone for Ionis, as it prepares for its first independent drug launch in its 35-year history. The approval was based on late-stage trial data showing that Tryngolza effectively reduced triglyceride levels and was generally well-tolerated.[36] Patients receiving the therapy were also less likely to experience pancreatitis, a severe and potentially fatal complication characterized by painful inflammation of the pancreas.[37]

## References

[edit]

1. ^ "Brett P Monia Chief Executive Officer/Co-Founder, Ionis Pharmaceuticals Inc". www.bloomberg.com. Retrieved 20 May 2022.
2. ^ "Elizabeth L. Hougen Chief Financial Officer & Executive VP-Finance, Ionis Pharmaceuticals, Inc". www.wsj.com. Retrieved 20 May 2022.
3. ^ "Ionis announces changes to its board of directors at annual meeting of stockholders". www.prnewswire.com (Press release). Retrieved 20 May 2022.
4. ^ "2023 Annual Report". IONIS Pharmaceuticals.
5. ^ a b "Ionis Pharmaceuticals, Inc. 2024 Form 10-K Annual Report". U.S. Securities and Exchange Commission. February 19, 2025. Retrieved 19 March 2025.
6. ^ a b Fikes, Bradley (December 18, 2015). "From Isis Pharma to Ionis". The San Diego Union-Tribune.
7. ^ Crooke, Stanley T. (July 21, 2011). "The Isis manifesto". Bioentrepreneur. doi:10.1038/bioe.2011.7.
8. ^ Fisher, Lawrence M. (March 8, 1992). "Making a Difference; A Green Light for Isis". The New York Times.
9. ^ Fisher, Lawrence M. (December 29, 1995). "Isis Drops Human Trials of a Genetic Drug". The New York Times.
10. ^ Jarvis, Lisa M. (April 17, 2006). "Back In The Game". Chemical & Engineering News.
11. ^ Workman, Karen (November 20, 2015). "When You're Named Isis for the Goddess, Not the Terror Group". The New York Times.
12. ^ "Ionis Pharma Spins Out Lipid Disorder Unit Akcea with Plans for IPO". Xconomy. March 27, 2017.
13. ^ Katzung, Bertram G. (2006). Basic and Clinical Pharmacology. New York: S&P Global. p. 817\. ISBN 978-0-07-145153-6.
14. ^ a b Bubela, Tania; McCabe, Christopher (July 21, 2014). "Value-Engineered Translation: Developing Biotherapeutics That Align With Health-System Needs". American Journal of Managed Care.
15. ^ a b c Jiang, Kevin (February 19, 2013). "Biotech comes to its 'antisenses' after hard-won drug approval : Spoonful of Medicine". Nature Medicine: Spoonful of Medicine Blog.
16. ^ "Public Statement on Vitravene (fomiversen): Withdrawal of the Marketing Authorization in the European Union" (PDF). European Medicines Agency. August 6, 2002.
17. ^ Filmore, David (June 2004). "Assessing antisense" (PDF). Modern Drug Discovery.
18. ^ a b c d Offord, Catherine (December 1, 2016). "Oligonucleotide Therapeutics Near Approval". The Scientist.
19. ^ "Company News; Isis Pharmaceuticals to Cut 40% of Workforce". The New York Times. Bloomberg News. January 11, 2005.
20. ^ Pollack, Andrew (September 7, 2007). "Two Biotech Companies Agree to Form a Joint Venture". The New York Times.
21. ^ Pollack, Andrew (January 8, 2008). "Genzyme Wins Cholesterol Drug Deal". The New York Times.
22. ^ "EMA committee shoots down Sanofi's cholesterol drug mipomersen". FierceBiotech. December 14, 2012.
23. ^ "Refusal of the marketing authorisation for Kynamro (mipomersen)" (PDF). European Medicines Agency. March 21, 2013.
24. ^ Fikes, Bradley J. (January 11, 2016). "Ionis takes back heart drug Kynamro". San Diego Union Tribune.
25. ^ "Ionis Sells Kynamro Rights to Kastle for Up to $95M+ Biotech from Bench to Business". Genetic Engineering News. May 3, 2016.
26. ^ Grant, Charley (December 27, 2016). "Surprise Drug Approval Is Holiday Gift for Biogen". The Wall Street Journal. ISSN 0099-9660.
27. ^ Garber, K (October 11, 2016). "Big win possible for Ionis/Biogen antisense drug in muscular atrophy". Nature Biotechnology. 34 (10): 1002–1003\. doi:10.1038/nbt1016-1002. PMID 27727217. S2CID 37479367.
28. ^ Wadman, Meredith (December 23, 2016). "Updated: FDA approves drug that rescues babies with fatal neurodegenerative disease". Science. doi:10.1126/science.aal0476.
29. ^ Tarr, Peter (December 24, 2016). "CSHL FDA approval of life-saving SMA drug is hailed by its researcher-inventor at CSHL". Cold Spring Harbor Laboratory.
30. ^ Saltzman, Jonathan; Weisman, Robert (December 16, 2017). "At a UMass lab, a eureka moment". The Boston Globe.
31. ^ "Biogen Shells Out $75M to Develop Ionis' Nusinersen after Positive Phase III Results". Genetic Engineering News. August 1, 2016.
32. ^ "Biogen and Ionis Pharmaceuticals Report Nusinersen Meets Primary Endpoint at Interim Analysis of Phase 3 ENDEAR Study in Infantile-Onset Spinal Muscular Atrophy" (Press release). Biogen. August 1, 2016.
33. ^ Gallagher, James (October 19, 2015). "Landmark Huntington's trial starts". BBC News.
34. ^ "Ionis wins FDA nod for triglyceride-lowering rare disease drug". Nature. doi:10.1038/s41587-024-02546-z. Retrieved 29 January 2025.
35. ^ Wosen, Jonathan (2024-12-19). "Ionis wins FDA approval for a rare disease therapy that lowers triglycerides". STAT. Retrieved 2024-12-28.
36. ^ Stroes, Erik S G; Alexander, Vickie; Prokopczuk, Ewa; Alexander Hegele, Robert; Arca, Marcello; Ballantyne, Christie M; Soran, Handrean; Prohaska, Thomas A; Xia, Shuting; Ginsberg, Henry N; Lee Witztum, Joseph; Tsimikas, Sotirios (2024-10-05). "6503 A Randomized, Placebo-Controlled Phase 3 Study of Olezarsen In Patients With Familial Chylomicronemia Syndrome: The Balance Trial". Journal of the Endocrine Society. 8 (Supplement_1). doi:10.1210/jendso/bvae163.546. ISSN 2472-1972. PMC 11453225.
37. ^ Wosen, Jonathan (2023-09-26). "Ionis inches toward first solo drug launch with late-stage trial success for rare genetic disease therapy". STAT. Retrieved 2024-12-28.

## External links

[edit]

* Official website
* Business data for Ionis Pharmaceuticals, Inc.:

* Google
* SEC filings
* Yahoo!

Authority control databases |

* ISNI

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