FDA Approves Sotatercept (Winrevair) for Pulmonary Arterial Hypertension

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The US FDA approval of sotatercept for PAH was announced by Merck on March 26, 2024.

The US Food and Drug Administration has approved sotatercept (NAME), a novel for the treatment of pulmonary arterial hypertension (PAH) in adult patients.

Announced on March 26, 2024 by Merck, the approval is based on data from the phase 3 STELLAR trial and comes less than 6 months after the company announced its New Biologics License Application for the agent had received a priority review designation from the FDA in September 2023.

A rare, progressive condition characterized by narrowing blood vessels within the lungs, approximately 500-1000 new cases of PAH are diagnosed each year in the US, according to the American Lung Association. Given the progressive nature of the disease, improving standard of care stands to have a significant impact on quality of life for these patients.

A multicenter, double-blind phase 3 trial, STELLAR enrolled and randomized 323 patients to sotatercept or placebo therapy for a 24-week treatment period. For inclusion in the trial, which was conducted in 91 sites across 21 countries, patients needed to have PAH and be receiving stable background therapy. Patients included in the trial were randomized in a 1:1 ratio to sotatercept or placebo therapy every 3 weeks for 24 weeks.

Of note, sotatercept dosing began at 0.3 mg per kilogram of body weight, with a target dose of 0.7 mg per kilogram of bodyweight.

The primary outcome of interest in the trial was the change from baseline to week 24 in 6-minute walking distance. The trial included 9 secondary outcomes, which were tested hierarchically in the following order: multicomponent improvement, change in pulmonary vascular resistance, change in NTproBNP level, improvement in WHO functional class, time to death or clinical worsening, French risk score, and changes in the PAH-SYMPACT Physical Impacts, Cardiopulmonary Symptoms, and Cognitive/Emotional Impacts domain score.

Upon analysis, results indicated the median change in 6-minute walk distance from baseline to week 24 in the trial was 34.4 meters (95% confidence interval [CI], 33.0 to 35.5) among the sotatercept group and 1.0 meters (95% CI, 0.3 to 3.5) among the placebo group. Investigators pointed out the Hodges–Lehmann estimate of the difference between the sotatercept and placebo groups in the change from baseline at week 24 in the 6-minute walk distance was 40.8 m (95% CI, 27.5 to 54.1; P<0.001).

In an analysis of secondary endpoints, results indicated the first 8 secondary outcomes of interest were significantly improved with sotatercept relative to placebo, but PAH-SYMPACT Cognitive/Emotional Impacts domain score was not significantly improved.

Subsequent analyses from the STELLAR trial provided further insight into the effects of the activin signaling inhibitor. At the European Respiratory Society International Congress 2023, Vallerie McLaughlin, MD, of the University of Michigan, presented data related to hemodynamics and echocardiography analyses demonstrating use was associated with improvements relative to the placebo cohort for mean pulmonary arterial (PA) pressure, PA compliance, pulmonary vascular resistance, mean right atrial pressure, and more.