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Merck has announced positive results from the Phase III ZENITH clinical trial of Winrevair (sotatercept-csrk) for the treatment of patients with pulmonary arterial hypertension (PAH) functional class (FC) III or IV at high risk of mortality who were on maximum tolerated background PAH therapy. According to the results, Winrevair reduced the relative risk of major morbidity and mortality events.1
In the study, Winrevair reduced the risk of a composite of all-cause death, lung transplantation, and hospitalization. For patients treated with the therapy, only 17.4% experienced one or more major morbidity and mortality events compared to 54.7% in the placebo arm.
In a press release, Marc Humbert, MD, PhD, department of respiratory and intensive care medicine Hospital Bicêtre (AP-HP), University Paris-Saclay and Inserm Unit 999 said: “The ZENITH study represents the first PAH clinical trial with a primary endpoint comprised entirely of major outcome measures—all-cause death, lung transplantation and hospitalization for PAH. Winrevair had a significant and clinically meaningful impact on the composite of these outcomes, and together with the growing body of evidence from the clinical development program, these data support the practice-changing potential of Winrevair for a broad range of patients with PAH.”
According to Merck, this trial was stopped early due to overwhelming efficacy demonstrated in the primary endpoint. As a result, the key secondary endpoint of overall survival did not reach its heightened mark that was required to establish statistical significance at the interim analysis.
“The impressive results from ZENITH demonstrated that patients on Winrevair had a 76 percent 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,” Eliav Barr, MD, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories, said in the 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.”
Earlier in January, Merck announced it had ended another Phase III trial of Winrevair early. The HYPERION study, evaluating Winrevair in recently diagnosed adults with PAH FC II or III at intermediate or high risk of disease progression, was concluded after positive data emerged from ZENITH’s interim analysis as well as a review of the totality of data from the Winrevair clinical program to date. Patients will now be able to receive Winrevair through the SOTERIA open-label extension study.2
In an earlier press release, Barr said: “Based on the strong, positive interim efficacy data from the ZENITH trial, as well as the totality of available WIinrevair data, we concluded that it would not be ethical to continue the HYPERION study. We are grateful to the dedicated community of patients who participated in these studies and are pleased to offer the option of receiving Winrevair through the Phase III SOTERIA open-label extension study.”
Merck plans to share results from the HYPERION study later this year.
References
1. WINREVAIR™ (sotatercept-csrk) Reduced the Risk of a Composite of All-Cause Death, Lung Transplantation and Hospitalization for Pulmonary Arterial Hypertension (PAH) by 76% Compared to Placebo in the Phase 3 ZENITH Trial. News release. Merck. March 31, 2025. Accessed April 1, 2025. https://www.merck.com/news/winrevair-sotatercept-csrk-reduced-the-risk-of-a-composite-of-all-cause-death-lung-transplantation-and-hospitalization-for-pulmonary-arterial-hypertension-pah-by-76-compared-to-placebo-i/
2. Merck Announces Decision to Stop Phase 3 HYPERION Trial Evaluating WINREVAIR™ (sotatercept-csrk) Early and Move to Final Analysis. News release. Merck. January 30, 2025. Accessed April 1, 2025. https://www.merck.com/news/merck-announces-decision-to-stop-phase-3-hyperion-trial-evaluating-winrevair-sotatercept-csrk-early-and-move-to-final-analysis/