Sotatercept's FDA Approval a New Chapter for Pulmonary Arterial Hypertension

The FDA approved sotatercept (Winrevair) for treating pulmonary arterial hypertension (PAH) in adults, Merck announced on Tuesday.

A novel activin signaling inhibitor, sotatercept is indicated to increase exercise capacity, improve World Health Organization (WHO) functional class, and reduce the risk of clinical worsening events for people with WHO group 1 pulmonary hypertension.

"Sotatercept added to background therapy has the potential to become a new standard of care option for patients with pulmonary arterial hypertension," said Aaron Waxman, MD, PhD, of Brigham and Women's Hospital in Boston, in the company's press release.

The activin signaling inhibitor works by targeting the pro-proliferative and anti-proliferative signaling associated with pulmonary arterial wall and right ventricular remodeling in PAH. The biologic is labeled for subcutaneous injection every 3 weeks.

"This approval is an important milestone, as it offers healthcare providers a novel therapeutic option that targets a new PAH treatment pathway," said Marc Humbert, MD, PhD, of the Université Paris-Saclay, who, along with Waxman, was an investigator on the randomized STELLAR trial that supported sotatercept's approval.

PAH is a rare progressive disorder characterized by the narrowing or blockage of small pulmonary arteries, causing elevated blood pressure in pulmonary circulation and extra effort for the heart to pump. PAH is associated with high morbidity and mortality despite existing endothelin receptor antagonist and phosphodiesterase-5 inhibitor therapies.

In the STELLAR trial, sotatercept improved exercise capacity for PAH patients on background therapy. Patients showed a placebo-adjusted 41-m improvement in 6-minute walk distance (6MWD) from baseline to week 24, as well as better odds of improvement in 6MWD, N-terminal pro-B-type natriuretic peptide, and WHO functional class (38.9% vs 10.1%, P<0.001).

Notably, patients in the sotatercept arm of the trial were much less likely to die or experience a clinical worsening event over a median 32.7 weeks (5.5% vs 26.3%, HR 0.16, 95% CI 0.08-0.35).

Merck said that due to the risks of erythrocytosis and severe thrombocytopenia, patients should have their hemoglobin and platelets monitored before each of their first five doses of sotatercept (monitoring for longer if values are unstable). Treatment should not be initiated if platelet count is <50,000/mm³. Other warnings and precautions in the labeling include serious bleeding, embryo-fetal toxicity, and impaired fertility.

According to the prescribing information, common adverse events associated with the drug in trials included nose bleeds, dizziness, headache, telangiectasia, diarrhea, rash, and erythema.

Merck said that sotatercept will be made available to specialty pharmacies by the end of April.

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