Positive results from phase III ZENITH study of Winrevair (sotatercept-csrk) in adults with pulmonary arterial hypertension – Merck Inc

Merck Inc.,( known as MSD outside of the United States and Canada), announced  positive topline results from the Phase III ZENITH study evaluating Winrevair (sotatercept-csrk) in adults with pulmonary arterial hypertension (PAH, WHO Group 1) functional class (FC) III or IV at high risk of mortality. ZENITH met its primary endpoint of time to first morbidity or mortality event (all-cause death, lung transplantation, or PAH worsening related hospitalization of ≥ 24 hours). In the study, Winrevair demonstrated a statistically significant and clinically meaningful reduction in the risk of morbidity or mortality events compared to placebo, both on top of background PAH therapy. Based on the strength of these results, an independent data monitoring committee has recommended ZENITH be stopped early and all participants be offered the opportunity to receive Winrevair through the SOTERIA open-label extension study. In preliminary assessment, adverse events and serious adverse events were balanced between the treatment groups.

“The ZENITH trial was designed to evaluate whether the addition of Winrevair, an activin signaling inhibitor, could reduce the risk of death, lung transplantation, or PAH hospitalizations for patients living with advanced PAH,” said Dr. Vallerie McLaughlin, Kim A Eagle MD Endowed Professor of Cardiovascular Medicine and Director, Pulmonary Hypertension Program, University of Michigan in Ann Arbor. “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, and we thank the investigators and patients for being part of this important study.”

Winrevair is currently approved in the U.S. and 36 countries based on the results from the Phase III STELLAR trial. Most recently, in November of this year,Winrevair was submitted for approval in Japan based on the STELLAR trial and results from an open-label PhaseIII study in Japanese patients.

Results from ZENITH will be presented at an upcoming medical meeting and will be submitted to regulatory authorities.

About ZENITH:  The ZENITH study (NCT04896008) is a global, double-blind, placebo-controlled clinical trial to evaluate Winrevair when added to maximum tolerated background PAH therapy on time to first event of all-cause death, lung transplantation, or PAH worsening related hospitalization of ≥ 24 hours, in participants with WHO FC III or IV PAH at high risk of mortality. ZENITH study inclusion criteria required Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) Lite 2.0 risk score of ≥9.

The study enrolled 172 participants, who were randomized in a 1:1 ratio to either Winrevair  plus background PAH therapy or placebo plus background PAH therapy. The primary composite outcome measure is time to first confirmed morbidity or mortality event. Events are defined as all-cause death, lung transplantation, or PAH worsening-related hospitalization of ≥ 24 hours. Secondary outcome measures include overall survival, transplant-free survival and several additional measures. Participants who have completed the ZENITH trial have the opportunity to receive sotatercept as part of the open-label, long-term extension study, SOTERIA (NCT04796337), consistent with that study’s eligibility criteria.