Key Takeaways
- FDA Grants Priority Review to Winrevair: Merck’s Winrevair (sotatercept-csrk) may receive a label update for pulmonary arterial hypertension (PAH) based on significant outcomes from the Phase III ZENITH trial.
- ZENITH Trial Demonstrates 76% Risk Reduction: Patients treated with Winrevair experienced a 76% reduction in the composite risk of death, lung transplantation, and ≥24-hour PAH-related hospitalization.
- Label Expansion Could Address Unmet Need in PAH: If approved, the updated indication may offer a disease-modifying option for high-risk PAH patients already on background therapy.
The FDA has accepted and granted Priority Review to a supplemental Biologics License Application (sBLA) for Merck’s Winrevair (sotatercept-csrk) for pulmonary arterial hypertension (PAH). The sBLA seeks to update the product label based on findings from the Phase III ZENITH trial (NCT04896008) in patients with PAH (Group 1 PH), World Health Organization functional class III or IV, at high risk of mortality and who are receiving maximum tolerated background PAH therapy.
According to the company, the updated label has the potential to include risk reduction benefits.1,2
How Could Winrevair’s Label Expansion Transform Pulmonary Arterial Hypertension Care?
“We are pleased that the FDA has accepted our sBLA for Winrevair and granted a priority review to consider an update to labeling for Winrevair to include the impressive results of ZENITH,” said Joerg Koglin, SVP, global clinical development, Merck Research Laboratories, in a press release. “There remains a significant unmet medical need for patients living with PAH who, despite being on background therapy, remain at higher risk of morbidity and mortality. The FDA’s Priority Review designation acceptance of our sBLA reinforces our confidence in Winrevair for a broad range of patients and represents a critical step toward advancing the treatment of PAH.”
ZENITH Trial Highlights Morbidity and Mortality Risk Reduction
- The global, double-blind, placebo-controlled ZENITH trial evaluated Winrevair as an add-on to maximum tolerated background PAH therapy, measuring time to the first event of all-cause death, lung transplantation, or PAH-related hospitalization ≥24 hours in 172 patients.
- Patients were randomly assigned in a 1:1 ratio to receive either Winrevair plus background PAH therapy or placebo plus background therapy.
- The primary endpoint of the trial was time to first confirmed major morbidity or mortality event.
- Key secondary endpoints included overall survival and transplant-free survival.1
- Results, first published in March, showed that Winrevair reduced the composite risk of death, lung transplant, and ≥24-hour PAH-related hospitalization by 76% compared to placebo (HR=0.24; p<0.0001).
- Due to the overwhelmingly positive results of the trial, the trial was stopped early, with patients transferring to the SOTERIA open-label extension study.
- Only 17.4% of patients treated with Winrevair experienced a morbidity or mortality event, compared to 54.7% in the placebo group.
Safety Profile and Adverse Events Remain Consistent
- Serious adverse events (AEs) occurred in 53.5% of the Winrevair group vs. 64% in the placebo group.
- Treatment-related AEs were reported in 65.1% of patients on Winrevair and 32.6% on placebo.
- Seven deaths were reported in the Winrevair arm versus 13 in the placebo arm.
- Common AEs included cutaneous telangiectasia, increased hemoglobin, and thrombocytopenia.2
PAH Remains a Rare but Life-Threatening Disease
According to the American Lung Association, PAH is most common in women between 30 and 60 years of age. In total, an estimated 500 to 1,000 people are diagnosed with PAH in the United States annually.3
The FDA has set a Prescription Drug User Fee Act target action date of October 25, 2025.1
“The impressive results from ZENITH demonstrated that patients on Winrevair had a 76% risk reduction in the composite of all-cause death, lung transplantation and hospitalization for PAH compared to placebo, with improvement observed early in treatment and increasing benefit throughout the study,” said Eliav Barr, SVP, head, global clinical development, chief medical officer, Merck Research Laboratories, in a March press release. “These results led to the ZENITH study being the first PAH clinical trial stopped early due to overwhelming efficacy, representing an important milestone in clinical research with promise for the PAH community.”2
References
1. FDA Grants Priority Review for WINREVAIR™ (sotatercept-csrk) to Update Label Based on Results From ZENITH Trial. Merck. July 2, 2025. Accessed July 7, 2025. https://www.merck.com/news/fda-grants-priority-review-for-winrevair-sotatercept-csrk-to-update-label-based-on-results-from-zenith-trial/
2. Winrevair Found to Significantly Reduce the Risk of Morbidity and Mortality in Patients with Pulmonary Arterial Hypertension. PharmExec. April 4, 2025. Accessed July 7, 2025. https://www.pharmexec.com/view/winrevair-found-significantly-reduce-risk-morbidity-mortality-patients-pulmonary-arterial-hypertension
3. Learn About Pulmonary Arterial Hypertension. American Lung Association. Accessed July 7, 2025. https://www.lung.org/lung-health-diseases/lung-disease-lookup/pulmonary-arterial-hypertension/learn-about-pulmonary-arterial-hypertension
