Merck announced that the US Food and Drug Administration (FDA) has approved an update to the US product label based on the Phase 3 ZENITH trial for WINREVAIR (sotatercept-csrk) for injection, 45mg, 60mg. WINREVAIR, an activin signaling inhibitor, is now FDA-approved for the treatment of adults with Pulmonary Arterial Hypertension (PAH, WHO Group 1 pulmonary hypertension) to improve exercise capacity and WHO Functional Class (FC), and reduce the risk of clinical worsening events, including hospitalisation for PAH, lung transplantation and death.

WINREVAIR was initially approved based on the pivotal STELLAR study in March 2024. Today’s approval expanded the indication of WINREVAIR to include components of the clinical worsening events: hospitalisation for PAH, lung transplantation and death.

In ZENITH, adding WINREVAIR to background therapy demonstrated a statistically significant and clinically meaningful 76 percent reduction in the risk of major morbidity and mortality outcomes in adults with PAH WHO FC III or IV compared to placebo (HR: 0.24; 95 percent CI: 0.13, 0.43; p<0.0001). The trial’s composite primary efficacy endpoint events—time to first occurrence of all-cause death, lung transplantation or PAH-worsening hospitalisation of ≥24 hours—occurred in 15 WINREVAIR-treated participants (17 percent) versus 47 placebo-treated participants (55 percent). Due to overwhelming efficacy based on the primary endpoint result, the ZENITH trial was stopped early at the interim analysis and patients were offered the opportunity to receive WINREVAIR through an open-label long-term follow-up study.

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

Healthcare providers should monitor haemoglobin and platelets before each dose of WINREVAIR for the first five doses, or longer if values are unstable, and periodically thereafter to determine if dose adjustments are required. WINREVAIR may increase haemoglobin and may lead to erythrocytosis, which, if severe, may increase the risk of thromboembolic events or hyperviscosity syndrome. WINREVAIR also may decrease platelet count and lead to severe thrombocytopenia, which may increase the risk of bleeding; thrombocytopenia occurred more frequently in patients also receiving prostacyclin infusion. Treatment should not be initiated if platelet count is <50,000/mm3.

“Merck’s leadership in PAH research is anchored in a comprehensive clinical programme that continues to advance science and deliver meaningful evidence for physicians and patients. This approval represents another step forward in our mission to deliver on the promise of WINREVAIR, an activin signaling inhibitor with an indication recognising its impact to adult patients with PAH on the risk of clinical worsening events, including death, lung transplantation and PAH hospitalisation," said Dr Joerg Koglin, Senior Vice President, Global Clinical Development, Merck Research Laboratories.