Phase III Hyperion Study Stopped Early

The decision to stop the HYPERION study prior to its scheduled completion was based on the positive results from the interim analysis of the ZENITH trial and a review of the totality of data from the Winrevair clinical program to date. The program’s external steering committee and Merck made this decision in light of these data, which will enable all study participants to have the opportunity to access Winrevair  Merck discussed this decision to stop the HYPERION study early with the FDA and has informed HYPERION study investigators.

"After closely reviewing the robust efficacy data across a broad spectrum of patients evaluated in the Winrevair clinical development program, the steering committee has unanimously concluded that the HYPERION study, evaluating Winrevair  versus placebo on top of background therapy, has lost clinical equipoise and should be stopped early,” said Dr. Vallerie McLaughlin**, Kim A Eagle MD Endowed Professor of Cardiovascular Medicine and Director, Pulmonary Hypertension Program, University of Michigan in Ann Arbor. “PAH is a progressive and debilitating disease with a high incidence of morbidity and mortality, and we look forward to continuing to evaluate these patients and any potential impact to the treatment landscape as a result of these data.”

“Based on the strong, positive interim efficacy data from the ZENITH trial, as well as the totality of available Winrevair  data, we concluded that it would not be ethical to continue the HYPERION study,” said Dr. Eliav Barr, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “We are grateful to the dedicated community of patients who participated in these studies and are pleased to offer the option of receiving Winrevair through the Phase III SOTERIA open-label extension study.”

About HYPERION; The HYPERION study (NCT04811092) is a global, double-blind, placebo-controlled clinical trial to evaluate Winrevair when added to background PAH therapy in newly diagnosed intermediate or high-risk PAH patients. Participants enrolled in the study had a diagnosis within 12 months of study screening of symptomatic PAH (WHO Group 1, classified as FC II or III) and presentation of idiopathic or heritable PAH, PAH associated with connective tissue diseases (CTD), drug- or toxin-induced PAH, post shunt correction PAH, or PAH presenting at least one year following the correction of congenital heart defects.

The study enrolled approximately 300 study 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 clinical worsening (TTCW) as measured by first confirmed morbidity or mortality event. Clinical worsening events are defined as all-cause death, non-planned PAH worsening-related hospitalization of ≥ 24 hours, atrial septostomy, lung transplantation, and deterioration in six-minute walk test from baseline combined with at least one of the following changes including worsening of WHO FC from baseline, signs/symptoms of increased right heart failure, addition of a background PAH therapy or change in the background PAH therapy delivery route to parenteral. Secondary outcome measures include improvement of six-minute walk distance (6MWD), improvement and maintenance or achievement of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and improvement in WHO FC or maintenance of WHO FC II as well as additional measures. Participants in the HYPERION trial will have the opportunity to receive WINREVAIR as part of the open-label, long-term extension study, SOTERIA (NCT04796337), consistent with that study’s eligibility criteria.