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Sotatercept
Clinical data
Trade namesWinrevair
Other namesACE-011, MK-7962, sotatercept-csrk
AHFS/Drugs.comMonograph
License data
Routes of
administration		Subcutaneous
ATC code
  • None
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 for the treatment of pulmonary arterial hypertension.[1] It is an activin signaling inhibitor,[1] based on the extracellular domain of the activin type 2 receptor expressed as a recombinant fusion protein with immunoglobulin Fc domain (ACTRIIA-Fc).[4] It is given by subcutaneous injection.[1]

The most common side effects include headache, epistaxis (nosebleed), rash, telangiectasia (spider veins), diarrhea, dizziness, and erythema (redness of the skin).[1][5]

Sotatercept was approved for medical use in the United States in March 2024,[1][6][7] and in the European Union in August 2024.[2][3][8]

Medical uses

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In the United States, sotatercept is indicated for the treatment of adults with pulmonary arterial hypertension (PAH, WHO Group 1).[1][5]

In the European Union, sotatercept, in combination with other pulmonary arterial hypertension therapies, is indicated for the treatment of pulmonary arterial hypertension in adults with WHO Functional Class (FC) II to III, to improve exercise capacity.[2]

Side effects

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The most common adverse reactions include headache, epistaxis, rash, telangiectasia, diarrhea, dizziness, and erythema.[1][5]

Sotatercept causes increases in hemoglobin (red blood cells).[5] High concentrations of red blood cells in blood may increase the risk of blood clots.[5] Sotatercept causes decreases in platelet count, which can result in bleeding problems.[5]

Based on findings in animal studies, sotatercept may impair female and male fertility and cause fetal harm when administered during pregnancy.[5]

History

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The US Food and Drug Administration (FDA) approved sotatercept based on evidence of safety and effectiveness from a clinical trial of 323 participants with PAH (WHO group 1 functional class II or III).[5] The trial was conducted at 126 sites in 21 countries—Argentina, Australia, Belgium, Brazil, Canada, the Czech Republic, France, Germany, Israel, Italy, Mexico, the Netherlands, New Zealand, Poland, Serbia, South Korea, Spain, Sweden, Switzerland, the United Kingdom, and the United States.[5] The study included 88 participants inside the United States (43 in the sotatercept group and 45 in the placebo group).[5]

Society and culture

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Sotatercept was approved for medical use in the United States in March 2024.[1][5]

In June 2024, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Winrevair, intended for the treatment of pulmonary arterial hypertension.[2][9][10] The applicant for this medicinal product is Merck Sharp & Dohme B.V.[2] Sotatercept was approved for medical use in the European Union in August 2024.[2][3][8]

Economics

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Following its approval in 2024, the list price of Winrevair as single-vial and double-vial kit was announced at US$14,000 per vial, with an estimated annual cost of $240,000 a year.[11]

Names

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Sotatercept is the international nonproprietary name.[12][13]

Sotatercept is sold under the brand name Winrevair.[1][5]

Research

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It was initially developed to increase bone density[14] but during its early development was found to increase hemoglobin and red blood cell counts,[15] and was subsequently studied for use in anemia associated with multiple conditions including beta thalassemia and multiple myeloma.[16][17][18] Development of this drug was superseded by the development of luspatercept (Reblozyl), a modified activin receptor type 2B (ACTRIIB-Fc) based ligand trap with improved properties for anemia.[19] Hypothesizing that this drug might block the effects of activin in promoting pulmonary vascular disease, this molecule was found to inhibit vascular obliteration in multiple models of experimental pulmonary hypertension, providing rationale to reposition sotatercept for PAH in the PULSAR and STELLAR clinical trials for PAH.[20]

References

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  1. ^ a b c d e f g h i j "Winrevair- sotatercept-csrk kit". DailyMed. 26 March 2024. Archived from the original on 25 April 2024. Retrieved 25 April 2024.
  2. ^ a b c d e f "Winrevair EPAR". European Medicines Agency (EMA). 27 June 2024. Retrieved 29 June 2024. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  3. ^ a b c "Winrevair Product information". Union Register of medicinal products. 27 August 2024. Retrieved 29 August 2024.
  4. ^ 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.
  5. ^ a b c d e f g h i j k l "Drug Trials Snapshots: Winrevair". U.S. Food and Drug Administration (FDA). 26 March 2024. Retrieved 29 August 2024. Public Domain This article incorporates text from this source, which is in the public domain.
  6. ^ "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.
  7. ^ "FDA Approves Merck's Winrevair (sotatercept-csrk), a First-in-Class Treatment for Adults with Pulmonary Arterial Hypertension (PAH, WHO* Group 1)" (Press release). Merck. 27 March 2024. Archived from the original on 27 March 2024. Retrieved 27 March 2024 – via Business Wire.
  8. ^ a b "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.
  9. ^ "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.
  10. ^ "Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 24-27 June 2024". European Medicines Agency (EMA). 28 June 2024. Archived from the original on 12 July 2024. Retrieved 12 July 2024.
  11. ^ 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.
  12. ^ World Health Organization (2010). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 64". WHO Drug Information. 24 (3). hdl:10665/74577.
  13. ^ World Health Organization (2011). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 65". WHO Drug Information. 25 (1). hdl:10665/74623.
  14. ^ 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.
  15. ^ 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.
  16. ^ 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.
  17. ^ 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.
  18. ^ 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.
  19. ^ 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.
  20. ^ 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.

Further reading

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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

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