Sotatercept

Sotatercept
Clinical data
Trade namesWinrevair
Other namesACE-011, MK-7962, sotatercept-csrk
AHFS/Drugs.comMonograph
MedlinePlusa624053
License data
Pregnancy
category
  • AU: D
Routes of
administration		Subcutaneous
ATC code
Legal status
Legal status
Identifiers
CAS Number
DrugBank
UNII
KEGG
Chemical and physical data
FormulaC3448H5264N920O1058S42
Molar mass77879.94 g·mol−1

Sotatercept, sold under the brand name Winrevair, is a medication used to treat pulmonary arterial hypertension. 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. It is administered via subcutaneous injection.

The most common side effects include headache, epistaxis (nosebleed), rash, telangiectasia (spider veins), diarrhea, dizziness, and erythema (redness of the skin).

Sotatercept was approved for medical use in the United States in March 2024, and in the European Union in August 2024. The US Food and Drug Administration considers it to be a first-in-class medication.

Medical uses

In the United States, sotatercept is indicated for the treatment of adults with pulmonary arterial hypertension (WHO group 1 pulmonary hypertension) to improve exercise capacity and WHO functional class, and reduce the risk of clinical worsening events, including hospitalization for pulmonary arterial hypertension, lung transplantation and death.

In the European Union, in combination with other pulmonary arterial hypertension therapies, sotatercept is indicated for the treatment of pulmonary arterial hypertension in adults with WHO Functional Class II to IV, to improve exercise capacity.

Side effects

Common side effects include headache, epistaxis (nosebleeds), rash, telangiectasia (spider veins), diarrhea, dizziness, and erythema (skin redness). Sotatercept increases hemoglobin levels, raising blood clot risk, and decreases platelet counts, potentially causing bleeding issues. Animal studies suggest it may impair fertility and cause fetal harm during pregnancy.

History

The US Food and Drug Administration (FDA) approved sotatercept in March 2024, based on a trial of 323 participants with pulmonary arterial hypertension (WHO group 1, functional class II to IV) across 126 sites in 21 countries, including Argentina, Australia, and the United States. The study compared 163 participants on sotatercept to 160 on placebo, with 88 US participants (43 sotatercept, 45 placebo). The FDA granted the application for sotatercept breakthrough therapy designation.

In August 2024, sotatercept was authorized for medical use in the European Union.

Society and culture

Economics

In 2024, Winrevair's US list price was $14,000 per vial, with an annual cost of approximately $240,000 (actual costs vary by dose, body weight, insurance, discounts, assistance programs, and country). Based on the CDA-AMC clinical review of the STELLAR trial, sotatercept yields an incremental cost-effectiveness ratio of $436,796 per QALY gained, with cost-effectiveness highly dependent on uncertain long-term survival benefits and requiring an approximately 95% price reduction to meet a $50,000 per QALY threshold.

Names

Sotatercept is the international nonproprietary name.

Sotatercept is sold under the brand name Winrevair.

Research

Initially developed to increase bone density, sotatercept was found to increase hemoglobin and red blood cell counts, leading to studies for anemia in beta thalassemia and multiple myeloma. Anemia research later shifted to luspatercept (Reblozyl), a modified activin receptor type 2B (ACTRIIB-Fc) ligand trap with better anemia treatment properties. 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 pulmonary arterial hypertension.

References

  1. ↑ "TGA eBS - Product and Consumer Medicine Information Licence". www.ebs.tga.gov.au.
  2. ↑ "Winrevair (Merck Sharp & Dohme (Australia) Pty Ltd)". Therapeutic Goods Administration (TGA). 9 December 2024. Retrieved 19 December 2024.
  3. ↑ "Winrevair sotatercept 45 mg powder for injection vial (433670)". Therapeutic Goods Administration (TGA). 9 November 2024. Retrieved 19 December 2024.
  4. ↑ "Summary Basis of Decision for Winrevair". Drug and Health Products Portal. 31 January 2025. Retrieved 10 July 2025.
  5. ↑ "Winrevair product information". Health Canada. 28 August 2024. Retrieved 27 December 2024.
  6. 1 2 3 4 5 6 7 "Winrevair- sotatercept-csrk kit". DailyMed. 26 March 2024. Archived from the original on 25 April 2024. Retrieved 25 April 2024.
  7. 1 2 3 4 5 "Winrevair EPAR". European Medicines Agency (EMA). 26 August 2026. Retrieved 26 August 2026. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  8. 1 2 "Winrevair Product information". Union Register of medicinal products. 27 August 2024. Retrieved 29 August 2024.
  9. ↑ 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. hdl:10072/423493. PMID 37269300.
  10. 1 2 3 4 5 6 7 8 "Drug Trials Snapshots: Winrevair". U.S. Food and Drug Administration (FDA). 26 March 2024. Archived from the original on 10 July 2024. Retrieved 29 August 2024. Public Domain This article incorporates text from this source, which is in the public domain.
  11. ↑ "Novel Drug Approvals for 2024". U.S. Food and Drug Administration (FDA). 29 April 2024. Archived from the original on 30 April 2024. Retrieved 30 April 2024.
  12. ↑ New Drug Therapy Approvals 2024 (PDF). U.S. Food and Drug Administration (FDA) (Report). January 2025. Archived from the original on 21 January 2025. Retrieved 21 January 2025.
  13. ↑ "Winrevair | European Medicines Agency (EMA)". www.ema.europa.eu. 28 June 2024. Retrieved 26 August 2026.
  14. ↑ "CY 2024 CDER Breakthrough Therapy Calendar Year Approvals" (PDF). U.S. Food and Drug Administration (FDA). 30 September 2024.
  15. ↑ "Winrevair Product information". Union Register of medicinal products. 27 August 2024. Retrieved 29 August 2024.
  16. ↑ "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.
  17. ↑ Cohen, Joshua. "Winrevair Gains Approval For Pulmonary Arterial Hypertension, But High Price Could Limit Uptake". Forbes. Archived from the original on 6 April 2024. Retrieved 6 April 2024.
  18. ↑ "Pharmacoeconomic Review", Sotatercept (Winrevair): Therapeutic area: Pulmonary arterial hypertension (WHO group 1): Reimbursement Review, Canadian Agency for Drugs and Technologies in Health, February 2025, retrieved 26 August 2026
  19. ↑ "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 64". WHO Drug Information. 24 (3). 2010. hdl:10665/74577.
  20. ↑ "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 65". WHO Drug Information. 25 (1). 2011. hdl:10665/74623.
  21. ↑ Sherman, Matthew L.; Borgstein, Niels G.; Mook, Louisa; Wilson, Dawn; Yang, Yijun; Chen, Nianhang; 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.
  22. ↑ Dussiot, Michael; Maciel, Thiago T.; Fricot, Aurelie; Chartier, Celine; Negre, Olivier; Veiga, Joel; 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. PMC 7730561. PMID 24658077.
  23. ↑ Abdulkadyrov, Kudrat M.; Salogub, Galina N.; Khuazheva, Nuriet K.; Sherman, Matthew L.; Laadem, Abderrahmane; Barger, Rachel; 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. PMC 4312883. PMID 24650009.
  24. ↑ Lan, Zehao; Lv, Zhaohua; Zuo, Wanyun; Xiao, Yichao (September 2023). "From bench to bedside: The promise of sotatercept in hematologic disorders". Biomedicine & Pharmacotherapy. 165 115239. doi:10.1016/j.biopha.2023.115239. PMID 37516019.
  25. ↑ 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. Archived from the original on 4 November 2023. Retrieved 4 November 2023.
  26. ↑ Suragani, Rajasekhar N.V.S.; Cadena, Samuel M.; Cawley, Sharon M.; Sako, Dianne; Mitchell, Dianne; Li, Robert; 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.
  27. ↑ Yung, Lai-Ming; Yang, Peiran; Joshi, Sachindra; Augur, Zachary M.; Kim, Stephanie S.J.; Bocobo, Geoffrey A.l; et al. (May 2020). "ACTRIIA-Fc rebalances activin/GDF versus BMP signaling in pulmonary hypertension". Science Translational Medicine. 12 (543) eaaz5660. doi:10.1126/scitranslmed.aaz5660. PMC 8259900. PMID 32404506.

Note

    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