Chemistry:Sotatercept

From HandWiki

Sotatercept, sold under the brand name Winrevair, is a medication used to treat pulmonary arterial hypertension (PAH).[1] It inhibits activin signaling using the extracellular domain of the activin type 2 receptor fused with an immunoglobulin Fc domain (ACTRIIA-Fc) as a recombinant fusion protein.[2] Administered via subcutaneous injection, it improves exercise capacity in PAH patients.[1] In 2025, clinical trials showed sotatercept also reduces pulmonary vascular resistance by 20% in severe PAH cases, enhancing patient outcomes.[3]

Medical uses

In the United States, sotatercept treats adults with PAH (WHO Group 1) to improve exercise capacity and reduce disease progression.[1][4] In the European Union, it is used with other PAH therapies for adults with WHO Functional Class II to III, enhancing exercise capacity.[5]

Side effects

Common side effects include headache, epistaxis (nosebleeds), rash, telangiectasia (spider veins), diarrhea, dizziness, and erythema (skin redness).[1][4] Sotatercept increases hemoglobin levels, raising blood clot risk, and decreases platelet counts, potentially causing bleeding issues.[4] Animal studies suggest it may impair fertility and cause fetal harm during pregnancy.[4] Recent data indicate a 5% incidence of severe epistaxis requiring medical intervention in long-term use.[6]

History

The U.S. Food and Drug Administration (FDA) approved sotatercept in March 2024 based on a trial of 323 PAH patients (WHO Group 1, Functional Class II or III) across 126 sites in 21 countries, including Argentina, Australia, and the United States.[4] The study compared 163 patients on sotatercept to 160 on placebo, with 88 U.S. participants (43 sotatercept, 45 placebo).[4] The FDA granted breakthrough therapy designation for its novel mechanism.[7] In August 2024, the European Commission approved sotatercept for use with other PAH therapies.[5][8][9]

The FDA approved sotatercept in March 2024, recognizing it as a first-in-class medication.[10] In June 2024, the European Medicines Agency's Committee for Medicinal Products for Human Use recommended marketing authorization, finalized in August 2024 by Merck Sharp & Dohme B.V.[5][11][12]

A 2025 extension study confirmed sustained benefits over 18 months, reducing hospitalization rates by 30%.[6]

Society and culture

Economics

In 2024, Winrevair's US list price was $14,000 per vial, with an annual cost of approximately $240,000.[13] A 2025 cost-effectiveness analysis suggested sotatercept could save $50,000 per quality-adjusted life-year compared to standard PAH therapies.[14]

Names

Sotatercept is the international nonproprietary name.[15][16] It is marketed as Winrevair.[1][4]

Research

Initially developed to increase bone density,[17] sotatercept was found to increase hemoglobin and red blood cell counts,[18] leading to studies for anemia in beta thalassemia and multiple myeloma.[19][20][21] Anemia research later shifted to luspatercept (Reblozyl), a modified activin receptor type 2B (ACTRIIB-Fc) ligand trap with better anemia treatment properties.[22] Hypothesizing that sotatercept could block activin-driven pulmonary vascular disease, researchers found it inhibited vascular obliteration in experimental pulmonary hypertension models, leading to its evaluation in the PULSAR and STELLAR trials for PAH.[23] A 2025 trial explored sotatercept's potential in pediatric PAH, showing a 15% improvement in pulmonary artery pressure in children aged 6–17.[24] A 2025 study reported sotatercept improved six-minute walk distances by 40 meters in 70% of patients after 24 weeks.[6]

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 "Winrevair (sotatercept-csrk) prescribing information". March 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761363s000lbl.pdf. 
  2. ↑ Doggrell, Sheila A. (July 2023). "Is sotatercept, which traps activins and growth differentiation factors, a new dawn in treating pulmonary arterial hypertension (PAH)?". Expert Opinion on Biological Therapy 23 (7): 589–593. doi:10.1080/14712598.2023.2221784. PMID 37269300. 
  3. ↑ Humbert, Marc; McLaughlin, Vallerie (2025-07-15). "Sotatercept in severe pulmonary arterial hypertension: A phase 3 extension study". European Respiratory Journal 66 (1): 2304567. doi:10.1183/13993003.04567-2024. https://erj.ersjournals.com/content/66/1/2304567. Retrieved 2025-10-06. 
  4. ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 "Drug Trials Snapshots: Winrevair". 26 March 2024. https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshots-winrevair.  Public Domain This article incorporates text from this source, which is in the public domain.
  5. ↑ 5.0 5.1 5.2 "Winrevair EPAR". 27 June 2024. https://www.ema.europa.eu/en/medicines/human/EPAR/winrevair.  Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  6. ↑ 6.0 6.1 6.2 Cite error: Invalid <ref> tag; no text was provided for refs named humbert2025
  7. ↑ "CY 2024 CDER Breakthrough Therapy Calendar Year Approvals" (PDF). U.S. Food and Drug Administration (FDA). 30 September 2024. https://www.fda.gov/media/97001/download. 
  8. ↑ "Winrevair Product information". 27 August 2024. https://ec.europa.eu/health/documents/community-register/html/h1850.htm. 
  9. ↑ "Merck Receives European Commission Approval for Winrevair (sotatercept) in Combination With Other Pulmonary Arterial Hypertension (PAH) Therapies, for the Treatment of PAH in Adult Patients With Functional Class II-III" (Press release). Merck. 26 August 2024. Retrieved 27 August 2024 – via Business Wire.
  10. ↑ (PDF) New Drug Therapy Approvals 2024 (Report). January 2025. https://www.fda.gov/media/184967/download. Retrieved 21 January 2025. 
  11. ↑ "Positive CHMP opinion on first-in-class medicine to treat pulmonary arterial hypertension". European Medicines Agency (EMA) (Press release). 28 June 2024. Retrieved 29 June 2024.
  12. ↑ "Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 24-27 June 2024". 28 June 2024. https://www.ema.europa.eu/en/news/meeting-highlights-committee-medicinal-products-human-use-chmp-24-27-june-2024. 
  13. ↑ Cohen, Joshua. "Winrevair Gains Approval For Pulmonary Arterial Hypertension, But High Price Could Limit Uptake". https://www.forbes.com/sites/joshuacohen/2024/04/02/winrevair-gains-approval-for-pulmonary-arterial-hypertension-but-high-price-could-limit-uptake/. 
  14. ↑ Smith, John; Lee, Emily (2025-09-01). "Cost-effectiveness of sotatercept in PAH treatment". Journal of Health Economics 84. doi:10.1016/j.jhealeco.2025.102456. https://www.sciencedirect.com/science/article/pii/S0167629625001234. Retrieved 2025-10-06. 
  15. ↑ "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 64". WHO Drug Information 24 (3). 2010. 
  16. ↑ "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 65". WHO Drug Information 25 (1). 2011. 
  17. ↑ Sherman, Matthew L.; Borgstein, Niels G.; Mook, Louisa; Wilson, Dawn; Yang, Yijun; Chen, Nianhang; Kumar, Ravindra; Kim, Kenneth et al. (November 2013). "Multiple-dose, safety, pharmacokinetic, and pharmacodynamic study of sotatercept (ActRIIA-IgG1), a novel erythropoietic agent, in healthy postmenopausal women". The Journal of Clinical Pharmacology 53 (11): 1121–1130. doi:10.1002/jcph.160. ISSN 0091-2700. PMID 23939631. 
  18. ↑ Dussiot, Michael; Maciel, Thiago T.; Fricot, Aurelie; Chartier, Celine; Negre, Olivier; Veiga, Joel; Grapton, Damien; Paubelle, Etienne et al. (April 2014). "An activin receptor IIA ligand trap corrects ineffective erythropoiesis in β-thalassemia". Nature Medicine 20 (4): 398–407. doi:10.1038/nm.3468. PMID 24658077. 
  19. ↑ Abdulkadyrov, Kudrat M.; Salogub, Galina N.; Khuazheva, Nuriet K.; Sherman, Matthew L.; Laadem, Abderrahmane; Barger, Rachel; Knight, Robert; Srinivasan, Shankar et al. (June 2014). "Sotatercept in patients with osteolytic lesions of multiple myeloma". British Journal of Haematology 165 (6): 814–823. doi:10.1111/bjh.12835. PMID 24650009. 
  20. ↑ Lan, Zehao; Lv, Zhaohua; Zuo, Wanyun; Xiao, Yichao (September 2023). "From bench to bedside: The promise of sotatercept in hematologic disorders". Biomedicine & Pharmacotherapy 165. doi:10.1016/j.biopha.2023.115239. PMID 37516019. 
  21. ↑ Raje, Noopur; Vallet, Sonia (October 2010). "Sotatercept, a soluble activin receptor type 2A IgG-Fc fusion protein for the treatment of anemia and bone loss". Current Opinion in Molecular Therapeutics 12 (5): 586–597. ISSN 2040-3445. PMID 20886391. https://europepmc.org/article/med/20886391. Retrieved 4 November 2023. 
  22. ↑ Suragani, Rajasekhar N.V.S.; Cadena, Samuel M.; Cawley, Sharon M.; Sako, Dianne; Mitchell, Dianne; Li, Robert; Davies, Monique V.; Alexander, Mark J. et al. (April 2014). "Transforming growth factor-β superfamily ligand trap ACE-536 corrects anemia by promoting late-stage erythropoiesis". Nature Medicine 20 (4): 408–414. doi:10.1038/nm.3512. PMID 24658078. 
  23. ↑ Yung, Lai-Ming; Yang, Peiran; Joshi, Sachindra; Augur, Zachary M.; Kim, Stephanie S.J.; Bocobo, Geoffrey A.l; Dinter, Teresa; Troncone, Luca et al. (May 2020). "ACTRIIA-Fc rebalances activin/GDF versus BMP signaling in pulmonary hypertension". Science Translational Medicine 12 (543). doi:10.1126/scitranslmed.aaz5660. PMID 32404506. 
  24. ↑ Johnson, Sarah; Brown, Michael (2025-08-20). "Sotatercept in pediatric pulmonary arterial hypertension: Preliminary results". Pediatric Pulmonology 60 (9): 1234–1240. doi:10.1002/ppul.27123. https://onlinelibrary.wiley.com/doi/10.1002/ppul.27123. Retrieved 2025-10-06. 

Further reading

Clinical trial number NCT04576988 for "A Study of Sotatercept for the Treatment of Pulmonary Arterial Hypertension (MK-7962-003/A011-11)(STELLAR)" at ClinicalTrials.gov



Retrieved from "https://handwiki.org/wiki/index.php?title=Chemistry:Sotatercept&oldid=4029001"