Merck (MSD) has announced positive topline results from the Phase 3 ZENITH study, evaluating Winrevair (sotatercept-csrk) in adult patients with pulmonary arterial hypertension (PAH) at high risk of mortality. The study met its primary endpoint, demonstrating a statistically significant and clinically meaningful reduction in the risk of morbidity or mortality events compared to placebo, when added to background PAH therapy.
The ZENITH trial focused on patients with PAH (WHO Group 1) functional class (FC) III or IV, who were at high risk of mortality. The primary endpoint was the time to the first morbidity or mortality event, including all-cause death, lung transplantation, or PAH worsening-related hospitalization of 24 hours or more.
Early Termination Due to Overwhelming Efficacy
Based on the strength of the positive results, the independent data monitoring committee recommended that the ZENITH trial be stopped early. All participants are being offered the opportunity to receive Winrevair through the SOTERIA open-label extension study. Preliminary assessments indicated that adverse events and serious adverse events were balanced between the treatment groups.
Expert Commentary
"PAH is a serious, progressive disease with a high incidence of morbidity and mortality," said Dr. Eliav Barr, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. "Based on the primary endpoint demonstrating overwhelming efficacy, all ZENITH study participants will be offered the opportunity to receive WINREVAIR. These findings are impressive and support the potential of WINREVAIR to be practice-changing in the management of PAH."
Dr. Vallerie McLaughlin, Kim A Eagle MD Endowed Professor of Cardiovascular Medicine and Director, Pulmonary Hypertension Program, University of Michigan in Ann Arbor, added, "This is the first study in PAH in which the interim analysis led to an early conclusion of the study due to overwhelming efficacy. WINREVAIR has brought significant optimism to the field."
Winrevair's Current Status
Winrevair is currently approved in the U.S. and 36 countries, based on the results from the Phase 3 STELLAR trial. In November, Merck submitted Winrevair for approval in Japan, supported by the STELLAR trial and an open-label Phase 3 study in Japanese patients.
Merck plans to present the full results from the ZENITH trial at an upcoming medical meeting and will submit them to regulatory authorities for review and potential approval in other regions.
