The European Commission has granted approval to sotatercept (Winrevair; Merck) for the treatment of pulmonary arterial hypertension (PAH) in adult patients classified as World Health Organization (WHO) Functional Class II to III. This approval makes sotatercept the first activin signaling inhibitor therapy available for PAH in Europe.
The approval is based on data from the Phase 3 STELLAR trial, which demonstrated significant improvements in exercise capacity and a reduced risk of clinical worsening or death when sotatercept was added to background PAH therapy. The decision follows the FDA's approval of sotatercept in the United States earlier this year.
Clinical Impact
"Pulmonary arterial hypertension is a devastating disease for patients, who suffer from debilitating symptoms that severely limit their daily activities," said Dr. Marc Humbert, Professor of Medicine and Director of Pulmonary Hypertension Reference Center at Université Paris-Saclay. "Based on the Phase 3 STELLAR study, adding WINREVAIR to background PAH therapy improved exercise capacity, reduced the risk of death or clinical worsening events and improved functional class compared to background PAH therapy alone."
STELLAR Trial Results
The STELLAR trial was a randomized, multicenter, double-blind study involving 323 patients who were randomized 1:1 to receive either sotatercept or placebo. The primary endpoint was the change in 6-minute walk distance from baseline to week 24.
The results showed that sotatercept significantly improved the 6-minute walk distance by a mean of 40.1 meters (95% CI, 29.9-50.2) compared to a decrease of 1.4 meters in the placebo group. Furthermore, sotatercept reduced the risk of death or nonfatal clinical worsening by 84% compared to placebo (HR, 0.16; 95% CI, 0.08-0.35).
Administration and Adverse Events
Sotatercept is administered via subcutaneous injection once every three weeks and can be self-administered by the patient or a caregiver. The most common adverse reactions reported in the trial (≥10% of patients and at least 5% more than placebo) were headache (24.5% vs 17.5%), epistaxis (22.1% vs 1.9%), rash (20.2% vs 8.1%), telangiectasia (16.6% vs 4.4%), diarrhea (15.3% vs 10%), dizziness (14.7% vs 6.2%), and erythema (13.5% vs 3.1%).
Researchers noted that increases in hemoglobin levels, a known effect of sotatercept, were manageable with dose adjustments and were not associated with treatment discontinuations.
