FDA Grants Priority Review for Sotatercept in Pulmonary Arterial Hypertension

The FDA has accepted for priority review Merck’s biologics license application (BLA) for sotatercept to treat adult patients with pulmonary arterial hypertension (PAH). The FDA has set a Prescription Drug User Fee Act (PDUFA), or target action, date of March 26, 2024.

Pulmonary arterial hypertension is a rare, progressive and life-threatening disease in which blood vessels in the lungs narrow, causing strain on the heart. About 40,000 people in the United States are living with PAH. The five-year mortality rate is about 43%.

PAH is caused by the growth of cells in the arterial walls in the lung, leading to narrowing and abnormal constriction. Sotatercept is a first-in-class activin signaling inhibitor. In preclinical models, it has been shown to modulate vascular cell proliferation, reversing vascular and right ventricle remodeling.

“Despite advances in the treatment of PAH over the last two decades, there is still a significant need to improve outcomes for patients,” Joerg Koglin, M.D., senior vice president, global clinical development, Merck Research Laboratories, said in a press release.

The submission is based on the results of the STELLAR phase 3 trial. In the trial, sotatercept on top of background therapy demonstrated a statistically significant and clinically meaningful improvement in six-minute walk distance and eight of nine secondary outcome measure. Data were presented earlier this year at the American College of Cardiology meeting and published in the New England Journal of Medicine.

The primary endpoint of the study was the 6-minute walk test, and sotatercept improved exercise capacity, increasing 6-minute walk distance by 40.8 meters.

In the trial, 38.9% of patients in the sotatercept group achieved iimprovement at week 24 — which was defined as improvement in six-minute walk test, improvement in N-terminal pro-B-type natriuretic peptide level, and either improvement in WHO functional class or maintenance of WHO FC II — compared with 10.1% in the placebo group. Additionally, with a median follow-up of 32.7 weeks, nine of 163 patients in the sotatercept group died or experienced a clinical worsening event versus 42 of 160 patients in the placebo group.

Earlier in September, Merck presented new analyses from the STELLAR study and interim results from the open-label SOTERIA study at the European Respiratory Society International Congress 2023. An exploratory post-hoc analysis of right heart catheterization and echocardiography data from patients in the STELLAR study showed treatment with sotatercept reduced right heart size and improved right-ventricular function and hemodynamic status.

An interim analysis of the ongoing phase 3 SOTERIA found that sotatercept was well-tolerated and the safety profile was similar to previous studies. Treatment-emergent adverse events (TEAEs) occurred in 81.7% of participants. Serious TEAEs occurred in 19.3% of participants but only a small proportion lead to treatment discontinuation or death. Additionally, 22.7% (n=93/409) of participants experienced a telangiectasia event (small, widened blood vessels on the skin).