• 29 Oct 2025
• Admin
• News Article

FDA Expands Merck’s Winrevair Label to Include Major Morbidity and Mortality Outcomes in Pulmonary Arterial Hypertension

Merck, known as MSD outside the United States and Canada, announced that the U.S. Food and Drug Administration (FDA) has approved an update to the U.S. product label for Winrevair (sotatercept-csrk) for injection, 45 mg and 60 mg, based on results from the Phase 3 ZENITH trial.

Winrevair, an activin signaling inhibitor, is now FDA-approved for the treatment of adults with pulmonary arterial hypertension (PAH, WHO Group 1) to improve exercise capacity, WHO functional class (FC), and to reduce the risk of clinical worsening events — including hospitalization for PAH, lung transplantation, and death.

The therapy was initially approved in March 2024 following the pivotal STELLAR study. The latest FDA decision expands the indication to include additional clinical worsening components supported by new efficacy data from ZENITH.

ZENITH Trial Findings

The global, double-blind, placebo-controlled ZENITH study (NCT04896008) enrolled 172 adults with PAH WHO FC III or IV at high mortality risk, randomized 1:1 to Winrevair (n=86) or placebo (n=86), both with background PAH therapy.

Results showed that adding Winrevair reduced the risk of major morbidity and mortality by 76% compared with placebo (HR: 0.24; 95% CI: 0.13–0.43; p<0.0001).

• Event incidence: 17% (Winrevair) vs 55% (placebo).
• Primary endpoint: time to first occurrence of all-cause death, lung transplantation, or PAH-related hospitalization ≥24 hours.
• Study termination: halted early due to overwhelming efficacy at interim analysis; participants transitioned to an open-label extension.

Participants had a mean disease duration of eight years. The most common PAH etiologies were idiopathic (50%), connective tissue disease-associated (28%), and heritable (11%). Most patients were on triple therapy (72%) and prostacyclin infusion (59%).

Expert Commentary

“For patients with PAH, the risk of serious events such as hospitalization, transplantation, or death remains unacceptably high despite maximal therapy,” said Dr. Vallerie McLaughlin, Director, Pulmonary Hypertension Program, University of Michigan. “Results from ZENITH add to the growing evidence supporting Winrevair as a potential standard of care.”

Dr. Joerg Koglin, Senior Vice President, Global Clinical Development, Merck Research Laboratories, added:
“This approval underscores Merck’s leadership in PAH research and our commitment to advancing activin signaling inhibition as a therapeutic pathway for improving long-term outcomes in PAH.”

Safety Profile

Healthcare providers are advised to monitor hemoglobin and platelet counts before each dose for the first five administrations (or longer if unstable) and periodically thereafter.

Key safety considerations:

• Increased hemoglobin may lead to erythrocytosis and elevated risk of thromboembolic events or hyperviscosity syndrome.
• Reduced platelet count may lead to thrombocytopenia and increased bleeding risk, particularly among patients on prostacyclin infusion therapy.
• Treatment should not be initiated if platelet count <50,000/mm³.

Common adverse reactions (≥10% incidence and ≥5% more than placebo) included:

• Infections (67.4% vs 44.2%)
• Epistaxis (45.3% vs 9.3%)
• Diarrhea (25.6% vs 17.4%)
• Telangiectasia (25.6% vs 3.5%)
• Increased hemoglobin (15.1% vs 1.2%)
• Rash, erythema, and gingival bleeding (each ≈10%)

Median treatment duration was 435 days for Winrevair vs 268 days for placebo. Discontinuation due to adverse events occurred in 1% vs 5%, respectively.

Mechanism and Clinical Role

Winrevair is the first activin signaling inhibitor approved for PAH, acting to rebalance pro- and anti-proliferative signaling in pulmonary vasculature. Preclinical models demonstrated associations with thinner vessel walls, partial reversal of right ventricular remodeling, and improved hemodynamics.

Winrevair is developed under a licensing agreement with Bristol Myers Squibb.