Merck Announces Positive Top-Line Results from Phase 3 ZENITH Trial of WINREVAIR (sotatercept-csrk) in High-Risk Pulmonary Arterial Hypertension Patients, Published Simultaneously in The New England Journal of Medicine

Roway, New Jersey, USA,2025Year3Month31Day– MSD (the corporate name of Merck & Co., Inc., located in Rahway, New Jersey, U.S.) released the Phase III ZENITH study results for the first time. The study evaluated the efficacy of WINREVAIR (sotatercept-csrk) compared to placebo in adult patients with pulmonary arterial hypertension (PAH, Group 1 PH) who are at high risk of death and receiving maximum tolerated background PAH therapy, with WHO* functional class (FC) III or IV.

The study results were presented as a breakthrough oral presentation at the American College of Cardiology’s Annual Scientific Session (ACC.25) and published simultaneously in The New England Journal of Medicine. In November 2024, MSD announced the early termination of the ZENITH study based on positive results, following the recommendation of the independent data monitoring committee. Participants will be offered the opportunity to receive WINREVAIR treatment through the SOTERIA open-label extension study.

      ZENITH Study (NCT04896008) is a pivotal Phase III multicenter, double-blind, placebo-controlled trial evaluating the efficacy of WINREVAIR compared to placebo in WHO FC III or IV adult patients at high risk of mortality and receiving maximum tolerated background PAH therapy. The primary endpoint of the study is the time to the first event of morbidity or death (all-cause mortality, lung transplantation, or hospitalization related to PAH worsening lasting ≥24 hours), with secondary endpoints including overall survival, transplant-free survival, and several other additional metrics.

      "The ZENITH study is the first PAH clinical trial to use all-cause mortality, lung transplantation, and PAH-related hospitalization as primary endpoints," said Dr. Marc Humbert from the Department of Respiratory and Critical Care Medicine at Bicêtre Hospital, Paris-Saclay University. "WINREVAIR has demonstrated a significant and clinically meaningful impact on relevant study outcomes. Coupled with the growing body of evidence from clinical research programs, these data collectively support and validate the transformative treatment potential of WINREVAIR for patients with PAH."

      "The results of the ZENITH study are impressive, with relevant outcomes emerging early on and continuing to accumulate as the research progresses," said Dr. Eliav Barr, Senior Vice President of Merck Sharp & Dohme AG Laboratories, Head of Global Clinical Development, and Chief Medical Officer. "This has also led the ZENITH study to become the first PAH clinical trial to be terminated early due to significant results, marking a milestone in the field of clinical research and bringing hope to the PAH patient population."

      ZENITH is the second Phase III trial to demonstrate the efficacy of WINREVAIR in adult patients with PAH. The first was the Phase III STELLAR study, previously presented at the 2023 ACC meeting. The results of the ZENITH study will be shared with regulatory authorities around the world. Based on the results of the STELLAR study, WINREVAIR has already been approved in more than 40 countries.

      MSD announced in January 2025 that the Phase III HYPERION study was terminated early and moved directly into the final analysis phase. This study aimed to evaluate the efficacy of WINREVAIR in combination with background PAH therapy for newly diagnosed PAH FC II or III patients at moderate or high risk of disease progression. The decision to terminate the HYPERION study early was based on the positive interim results from the ZENITH study, as well as a comprehensive evaluation of the current WINREVAIR clinical program data. Results from the HYPERION study will be released later this year and presented at future medical conferences.

      *World Health Organization

      *As of now, WINREVAIR has not yet been officially approved in China.

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