- Source: Sotatercept
Sotatercept, sold under the brand name Winrevair is a medication used for the treatment of pulmonary arterial hypertension. It is an activin signaling inhibitor, based on the extracellular domain of the activin type 2 receptor expressed as a recombinant fusion protein with immunoglobulin Fc domain (ACTRIIA-Fc). It is given by 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.
Medical uses
In the United States, sotatercept is indicated for the treatment of adults with pulmonary arterial hypertension (PAH, WHO Group 1).
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.
Side effects
The most common adverse reactions include headache, epistaxis, rash, telangiectasia, diarrhea, dizziness, and erythema.
Sotatercept causes increases in hemoglobin (red blood cells). High concentrations of red blood cells in blood may increase the risk of blood clots. Sotatercept causes decreases in platelet count, which can result in bleeding problems.
Based on findings in animal studies, sotatercept may impair female and male fertility and cause fetal harm when administered during pregnancy.
History
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). 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. The study included 88 participants inside the United States (43 in the sotatercept group and 45 in the placebo group).
Society and culture
= Legal status
=Sotatercept was approved for medical use in the United States in March 2024.
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. The applicant for this medicinal product is Merck Sharp & Dohme B.V. Sotatercept was approved for medical use in the European Union in August 2024.
= Economics
=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.
= Names
=Sotatercept is the international nonproprietary name.
Sotatercept is sold under the brand name Winrevair.
Research
It was initially developed to increase bone density but during its early development was found to increase hemoglobin and red blood cell counts, and was subsequently studied for use in anemia associated with multiple conditions including beta thalassemia and multiple myeloma. 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. 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.
References
Further reading
"Role of Sotatercept in Management of Pulmonary Arterial Hypertension: The STELLAR Trial". American College of Cardiology.
Humbert, Marc; McLaughlin, Vallerie; Gibbs, J. Simon R.; Gomberg-Maitland, Mardi; Hoeper, Marius M.; Preston, Ioana R.; et al. (April 2021). "Sotatercept for the Treatment of Pulmonary Arterial Hypertension". New England Journal of Medicine. 384 (13): 1204–1215. doi:10.1056/NEJMoa2024277. PMID 33789009.
Humbert, Marc; McLaughlin, Vallerie; Gibbs, J. Simon R.; Gomberg-Maitland, Mardi; Hoeper, Marius M.; Preston, Ioana R.; et al. (January 2022). "Sotatercept for the treatment of pulmonary arterial hypertension: PULSAR open-label extension". European Respiratory Journal. 61 (1). doi:10.1183/13993003.01347-2022. ISSN 0903-1936. PMC 9816418. PMID 36041750.
Joshi, Sachindra R.; Liu, Jun; Bloom, Troy; Karaca Atabay, Elif; Kuo, Tzu-Hsing; Lee, Michael; et al. (May 2022). "Sotatercept analog suppresses inflammation to reverse experimental pulmonary arterial hypertension". Scientific Reports. 12 (1): 7803. Bibcode:2022NatSR..12.7803J. doi:10.1038/s41598-022-11435-x. ISSN 2045-2322. PMC 9098455. PMID 35551212.
Komrokji, Rami; Garcia-Manero, Guillermo; Ades, Lionel; Prebet, Thomas; Steensma, David P; Jurcic, Joseph G; et al. (February 2018). "Sotatercept with long-term extension for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes: a phase 2, dose-ranging trial". The Lancet Haematology. 5 (2): e63–e72. doi:10.1016/S2352-3026(18)30002-4. PMID 29331635.
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.
External links
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
Kata Kunci Pencarian:
- Sotatercept
- Acceleron Pharma
- List of drugs: Sj–So
- Pulmonary hypertension
- Merck & Co.
- Transforming growth factor beta
- Siddhartha Mukherjee
- Anti-Müllerian hormone
- GDF15
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