Merck has received a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) recommending an expanded indication for WINREVAIR™ (sotatercept) in adults with pulmonary arterial hypertension (PAH, WHO Group 1).
The expanded use, in combination with other PAH therapies, now includes adults in WHO Functional Class II, III, and IV, based on the Phase 3 ZENITH trial. The European Commission will review the recommendation, with a final decision expected in Q1 2026 for the EU, Iceland, Liechtenstein, and Norway.
The ZENITH trial, a global, double-blind, placebo-controlled study of 172 high-risk PAH adults, showed that WINREVAIR plus background therapy reduced major morbidity and mortality events—including all-cause death, lung transplantation, or PAH-worsening hospitalization ≥24 hours—by 76% compared to placebo.
The trial was stopped early due to overwhelming efficacy, and patients entered an open-label long-term follow-up. Secondary data from the Phase 3 STELLAR trial also supported the CHMP recommendation. Results were published in the New England Journal of Medicine.
WINREVAIR is the first and only activin signaling inhibitor approved for PAH, authorized in all 27 EU member states, Iceland, Liechtenstein, Norway, and over 50 countries.
In the U.S., the FDA updated its approval in October 2025 for adults with WHO Group 1 PAH to improve exercise capacity, functional class, and reduce clinical worsening events. The therapy modulates vascular proliferation, improves vessel wall thickness, partially reverses right ventricular remodeling, and enhances hemodynamics.
ZENITH participants primarily had idiopathic PAH (50%), connective tissue disease–associated PAH (28%), or heritable PAH (11%), mostly WHO Functional Class III (74%) or IV (26%), on background double or triple therapy including prostacyclin infusion. The primary endpoint was time to first confirmed major morbidity or mortality; secondary endpoints included overall survival and other measures.
Common adverse reactions included headache, epistaxis, rash, telangiectasia, diarrhea, dizziness, erythema, infections, increased hemoglobin, and gingival bleeding. Serious events like bleeding were more frequent in patients on prostacyclin or antithrombotic therapy.
PAH is a rare, progressive, life-threatening condition affecting around 90,000 people globally, characterized by constricted pulmonary arteries, elevated pulmonary blood pressure, and heart strain, with a five-year mortality of ~43%.
