Merck Announces Pivotal Phase 3 ZENITH Trial Evaluating WINREVAIR™ (sotatercept-csrk) Met Primary Endpoint at Interim Analysis

WINREVAIR met primary endpoint of time to first morbidity or mortality event for the treatment of patients with pulmonary arterial hypertension (PAH) functional class III or IV at high risk of mortality

Study to be stopped early and participants will be offered the opportunity to receive WINREVAIR

Second positive phase 3 trial adds to growing body of evidence for WINREVAIR, an activin signaling inhibitor therapy that targets an underlying cause of PAH

RAHWAY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, announced today positive topline results from the Phase 3 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.

“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, set a high evidentiary bar for studies of future candidates developed for the treatment of PAH and support the potential of WINREVAIR to be practice-changing in the management of PAH.”

“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 3 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 Phase 3 study in Japanese patients.

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

*World Health Organization
** Dr. McLaughlin is an investigator in the ZENITH trial and a paid consultant to Merck.

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.

About WINREVAIR ™ (sotatercept-csrk) for injection, for subcutaneous use, 45 mg, 60 mg

WINREVAIR is FDA-approved for the treatment of adults with pulmonary arterial hypertension (PAH, WHO Group 1) to increase exercise capacity, improve WHO functional class (FC) and reduce the risk of clinical worsening events. WINREVAIR is the first activin signaling inhibitor therapy approved to treat PAH. WINREVAIR improves the balance between pro-proliferative and anti-proliferative signaling to modulate vascular proliferation. In preclinical models, WINREVAIR induced cellular changes that were associated with thinner vessel walls, partial reversal of right ventricular remodeling, and improved hemodynamics.

WINREVAIR is the subject of a licensing agreement with Bristol Myers Squibb.