FDA Approves Sotatercept to Treat Patients with Pulmonary Arterial Hypertension

The FDA has approved Merck’s Sotatercept-csrk (Winrevair) for the treatment of patients with pulmonary arterial hypertension (PAH), according to a Merck press statement. The approval comes after Sotatercept received a priority evaluation in September 2023.2 The FDA has designated the medicine as a breakthrough therapy and an orphan drug in the 45 mg and 60 mg doses.

PAH is a life-threatening condition that causes the blood vessels in the lungs to constrict, putting additional strain on the heart. It can lead to heart failure, restricted physical activity, and a shorter life expectancy, among other complications. Patients with Pulmonary Arterial Hypertension have a 5-year mortality rate of roughly 43%, and the illness affects approximately 40,000 people in the United States.

Sotatercept is an activin signaling inhibitor that has been shown to increase exercise capacity, improve WHO functional class, and lower the probability of clinically deteriorating episodes in PAH patients when combined with standard-of-care medication. The approval of Sotatercept-csrk is the first for an activin signaling inhibitor in PAH.

The approval is based on data from the multicenter, double-blind, phase 3 STELLAR trial, with findings published in The New England Journal of Medicine in April 2023.3 All individuals in the experiment were randomly assigned to receive either sotatercept (n = 163) or placebo (n = 160) every three weeks in addition to their standard-of-care PAH treatment. The primary endpoint of the trial was the change in 6-minute walking distance (6MWD) between baseline and week 24.

The researchers discovered a 34.4 m (95% CI, 33.0-35.5) median change in baseline for 6MWD by week 24 in the group that got sotatercept, compared to a 1.0 m (95% CI, -0.3 to 3.5) median change in 6MWD in the placebo group. The estimated difference in 6MWD after 24 weeks between the sotatercept and placebo groups was 40.8 m (95% confidence interval, 27.5-54.1).

“New therapeutic approaches for people with pulmonary arterial hypertension are still needed to support critical clinical goals such as boosting exercise capacity and functional class. Sotatercept combined with background therapy has the potential to become a new standard of care option for patients with pulmonary arterial hypertension, according to Aaron Waxman, MD, executive director of the Brigham and Women’s Hospital’s Center for Pulmonary Heart Diseases and investigator on the Phase 3 STELLAR study.

Secondary end points included multicomponent improvement, change in pulmonary vascular resistance, change in N-terminal pro-B-type natriuretic peptide level, improvement in World Health Organization functional class, time to death or clinical worsening, French risk score, and changes in the Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT) Physical Impacts, Cardiopulmonary Symptoms, and Cognitive/Emotional Impacts domain scores. Except for the PAH-SYMPACT Cognitive/Emotional Impacts domain score, all secondary end goals were significantly improved with sotatercept over placebo at week 24, with the exception of time to death or clinical deterioration.

Sotatercept side effects may include epistaxis, telangiectasia, dizziness, headache, rash, thrombocytopenia, elevated hemoglobin, and raised blood pressure. These occurred more frequently in the sotatercept group compared to the placebo. Given the possibility of side effects, health care professionals should evaluate hemoglobin and platelets before administering sotatercept during the first five doses.

“We are excited to see industry research leading to a better understanding of PAH and the development of a medicine in a novel treatment pathway that expands options for the patient community,” stated Matt Granato, president and CEO of the Pulmonary Hypertension Association.

The drug will be offered to all patients in April, according to the company’s press release.

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