Sotatercept

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Sotatercept
Clinical data
Trade names Winrevair
Other namesACE-011, MK-7962, sotatercept-csrk
License data
Routes of
administration 		Subcutaneous
ATC code
  • None
Legal status
Legal status
Identifiers
CAS Number
DrugBank
UNII
KEGG
Chemical and physical data
Formula C3448H5264N920O1058S42
Molar mass 77879.94 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). [2] It is given by subcutaneous injection. [1]

Contents

Sotatercept was approved for medical use in the United States in March 2024. [1] [3]

Medical uses

Sotatercept is indicated for the treatment of adults with pulmonary arterial hypertension (PAH, WHO Group 1). [1]

Society and culture

Names

Sotatercept is the international nonproprietary name. [4] [5]

Research

It was initially developed to increase bone density [6] but during its early development was found to increase hemoglobin and red blood cell counts, [7] and was subsequently studied for use in anemia associated with multiple conditions including beta thalassemia and multiple myeloma. [8] [9] [10] Development of this drug was superseded by the development of luspatercept (Reblozyl), a modified activin receptor type 2B (ACTRIIB-Fc) based ligand trap with improved properties for anemia. [11] 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. [12]

Society and culture

Economics

Following its approval in 2024, the list price of Winrevair as single-vial and double-vial kit was announced at $14,000 per vial, with an estimated annual cost of $240,000 a year. [13] An independent analysis by the Institute for Clinical and Economic Review determined that Winrevair would be cost-effective for treating PAH if priced between $18,700 and $36,200 annually. [14] ICER's report noted limitations in the available data, including a lack of longer-term studies, uncertainties around the drug's impact on mortality rates, and potential unknown side effects that have not yet surfaced. [15]

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References

  1. 1 2 3 4 5 6 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. ↑ "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. Retrieved 27 March 2024– via Business Wire.
  4. ↑ World Health Organization (2010). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 64". WHO Drug Information. 24 (3). hdl: 10665/74577 .
  5. ↑ World Health Organization (2011). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 65". WHO Drug Information. 25 (1). hdl: 10665/74623 .
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ Cohen, Joshua. "Winrevair Gains Approval For Pulmonary Arterial Hypertension, But High Price Could Limit Uptake". Forbes. Retrieved 6 April 2024.
  14. ↑ Cohen, Joshua. "Winrevair Gains Approval For Pulmonary Arterial Hypertension, But High Price Could Limit Uptake". Forbes. Retrieved 6 April 2024.
  15. ↑ "FirstWord". firstwordpharma.com. Retrieved 6 April 2024.

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


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