FDA Updates Merck’s WINREVAIR Label To Reflect Strong Phase 3 Outcomes In Pulmonary Arterial Hypertension

Merck, known as MSD outside the U.S. and Canada, announced that the U.S. FDA has approved an update to the U.S. product label for WINREVAIR™ (sotatercept-csrk) following positive results from the Phase 3 ZENITH trial. The update expands WINREVAIR’s indication for treating adults with pulmonary arterial hypertension (PAH, WHO Group 1) to now include a reduction in the risk of clinical worsening events, such as hospitalization for PAH, lung transplantation, and death. Initially approved in March 2024 based on the STELLAR study, this expanded approval reinforces WINREVAIR’s role as a key therapy for improving exercise capacity and WHO functional class in PAH patients.

“For patients with PAH, the risk of serious events such as hospitalization, transplantation or death remains unacceptably high despite being maximally treated with traditional therapies,” said Dr. Vallerie McLaughlin**, Kim A Eagle MD Endowed Professor of Cardiovascular Medicine and Director, Pulmonary Hypertension Program, University of Michigan in Ann Arbor. “Results from the pivotal ZENITH trial add to the growing body of data and support the potential for WINREVAIR as standard of care.”

In the ZENITH trial (N=172), patients receiving WINREVAIR alongside background therapy experienced a 76% reduction in the risk of major morbidity and mortality outcomes compared to placebo (HR: 0.24; 95% CI: 0.13–0.43; p<0.0001). The primary endpoint—time to first occurrence of all-cause death, lung transplant, or PAH hospitalization ≥24 hours—occurred in 17% of WINREVAIR patients versus 55% on placebo. Due to its strong efficacy, the study was stopped early at interim analysis, and all participants were offered continued treatment through an open-label follow-up study.

“Merck’s leadership in PAH research is anchored in a comprehensive clinical program that continues to advance science and deliver meaningful evidence for physicians and patients,” said Dr. Joerg Koglin, senior vice president, global clinical development, Merck Research Laboratories. “This approval represents another step forward in our mission to deliver on the promise of WINREVAIR, an activin signaling inhibitor with an indication recognizing its impact to adult patients with PAH on the risk of clinical worsening events, including death, lung transplantation and PAH hospitalization."

Healthcare providers are advised to monitor hemoglobin and platelet counts during early treatment to avoid complications such as erythrocytosis or thrombocytopenia. Common side effects observed in ZENITH included infections (67%), epistaxis (45%), diarrhea (26%), telangiectasia (26%), rash (10%), and gingival bleeding (10%). Despite longer treatment duration for WINREVAIR patients (435 vs. 268 days), discontinuations due to adverse events were minimal. These findings reinforce WINREVAIR’s strong efficacy and manageable safety profile as an advanced therapeutic option for adults with PAH.