Merck, referred to as MSD outside the U.S. and Canada, disclosed today successful topline findings from the Phase 3 ZENITH trial examining Winrevair (sotatercept-csrk) in adults diagnosed with pulmonary arterial hypertension (PAH, WHO Group 1), classified as functional class (FC) III or IV and at a heightened risk of death. The ZENITH trial successfully achieved its primary objective, which was the duration to the initial morbidity or mortality incident (encompassing any-cause death, lung transplant, or hospitalization due to PAH worsening for at least 24 hours). During the trial, Winrevair showed a statistically important and clinically significant decrease in morbidity or mortality risk compared to placebo while already on background PAH treatment. Due to the compelling results, an independent data monitoring board has advised terminating the ZENITH trial prematurely, permitting all participants to access Winrevair through the SOTERIA open-label extension project. Early evaluations indicate an even distribution of adverse and serious adverse events among treatment categories.
“PAH is a grave, progressive condition associated with high rates of illness and death,” stated Dr. Eliav Barr, Merck Research Laboratories’ senior vice president, overseeing global clinical development, and chief medical officer. “Given the primary objective’s demonstration of notable effectiveness, every ZENITH trial participant will have the chance to use Winrevair. These outcomes are compelling, setting an authoritative reference for future PAH candidate studies and underscoring Winrevair’s potential to transform PAH management.”
“The ZENITH research aimed to assess whether Winrevair, an activin signaling inhibitor, could lower risks of death, lung transplant, or PAH-related hospital stays among advanced PAH patients,” remarked Dr. Vallerie McLaughlin, affiliated with the University of Michigan’s Pulmonary Hypertension Program. “This marks the first PAH study where interim results prompted an early conclusion owing to strong efficacy. Winrevair has infused the field with optimism, and we extend gratitude to both investigators and patients involved in this significant study.”
Winrevair is currently sanctioned in the U.S. and 36 other nations based on Phase 3 STELLAR trial results. Recently, in November, it was submitted for approval in Japan involving evidence from both the STELLAR trial and a Japanese open-label Phase 3 study.
Findings from the ZENITH study will be shared at a forthcoming medical conference and proposed to regulatory bodies.
The ZENITH trial (NCT04896008) is a global, double-blind, placebo-controlled clinical study evaluating Winrevair when incorporated into maximized background PAH therapy on the timing of the first all-cause mortality, lung transplant, or 24-hour plus PAH exacerbation hospitalization incident, among those with WHO FC III or IV PAH facing high mortality risk. Inclusion standards for the ZENITH trial involved a REVEAL Lite 2.0 risk score of at least 9.
The trial involved 172 participants, randomly divided in equal parts to receive either Winrevair along with standard PAH treatment or a placebo with standard PAH treatment. The chief outcome being measured is the time to the first verified morbidity or mortality incident, defined as any-cause death, lung transplant, or hospitalization due to PAH exacerbation for at least 24 hours. Secondary outcomes considered encompass overall survival, survival without requiring transplants, and various additional metrics. Participants who completed the ZENITH trial can access sotatercept under the open-label, long-term extension study, SOTERIA (NCT04796337), adhering to that study’s requirements.
In the U.S., Winrevair has FDA approval for adult PAH treatment to enhance exercise capacity, improve WHO functional class (FC), and lessen the likelihood of clinical worsening incidents. Winrevair is the pioneering activin signaling inhibitor therapy authorized for PAH treatment. It adjusts vascular proliferation by striking a balance between pro-proliferative and anti-proliferative signaling. Preclinical testing indicated that Winrevair facilitated cellular alterations linked to thinner vessel walls, partial reversal of right ventricular remodeling, and better hemodynamics.
Winrevair is involved in a licensing deal with Bristol Myers Squibb.
Pulmonary arterial hypertension (PAH) is a seldom-seen, progressive, and deadly blood vessel disorder, marked by the constriction of minute pulmonary arteries and high blood pressure in pulmonary circulation. Roughly 40,000 U.S. individuals grapple with PAH. The affliction rapidly worsens for many patients, leading to considerable heart strain, restricted physical activity, heart failure, and a shorter life expectancy. For PAH patients, the five-year mortality rate is approximately 43%.
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