# 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. The US Food and Drug Administration (FDA) 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 (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. The FDA granted the application breakthrough therapy designation.
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 authorized 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.