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.

Sotatercept was approved for medical use in the United States in March 2024.

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

Legal status
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.

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. 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. 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.

Names
Sotatercept is the international nonproprietary name.

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 Development of this drug was superseded by the development of luspatercept (Reblozyl), a modified activin receptor type 2B (ACTRIIB-Fc) based ligand trap with improved properties for anemia.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.