Merck Halts Phase 3 HYPERION Trial of Winrevair Early After Positive ZENITH Results
核心洞察
Merck (搜索)'s Phase 3 HYPERION trial of Winrevair (sotatercept) for pulmonary arterial hypertension (搜索) (PAH) is stopped early due to positive results from the ZENITH trial.
The decision, made with the FDA and a steering committee, allows all HYPERION participants access to Winrevair in the SOTERIA extension study.
Winrevair, already approved in the U.S. and 38 countries, showed significant efficacy in the STELLAR and ZENITH trials, leading to the HYPERION halt.
Merck (搜索) has announced the early termination of its Phase 3 HYPERION trial evaluating Winrevair (sotatercept-csrk (搜索)) in adults with recently diagnosed pulmonary arterial hypertension (搜索) (PAH). The decision, influenced by positive interim results from the ZENITH trial and a comprehensive review of Winrevair's clinical program, aims to provide all study participants the opportunity to access the drug. This move reflects a growing confidence in Winrevair's efficacy and its potential to reshape the PAH treatment landscape.
The HYPERION study (NCT04811092) was a global, double-blind, placebo-controlled trial assessing Winrevair in combination with background PAH therapy in newly diagnosed patients with intermediate or high-risk PAH. Approximately 300 participants, diagnosed within 12 months and classified as WHO functional class II or III, were randomized to receive either Winrevair plus background therapy or placebo plus background therapy. The primary outcome was time to clinical worsening (TTCW), measured by the first confirmed morbidity or mortality event.
The decision to halt the trial was based on the compelling efficacy data observed in the ZENITH trial (NCT04896008). The ZENITH study evaluated Winrevair added to maximum tolerated background PAH therapy in patients with WHO FC III or IV PAH at high risk of mortality. Interim results demonstrated a statistically significant and clinically meaningful reduction in the risk of morbidity or mortality events compared to placebo, leading an independent data monitoring committee to recommend early termination.
"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.
Dr. Eliav Barr, senior vice president and head of global clinical development, chief medical officer, Merck (搜索) Research Laboratories, added, "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."
Participants in the HYPERION trial will have the opportunity to receive Winrevair as part of the open-label, long-term extension study, SOTERIA (NCT04796337). Findings from the HYPERION study are expected to be available later this year and will be presented at a future medical congress.
Winrevair is currently approved in the U.S. and 38 countries based on results from the Phase 3 STELLAR trial (NCT04576988). The STELLAR trial demonstrated that Winrevair significantly improved exercise capacity, as measured by the six-minute walk distance (6MWD) at 24 weeks, and reduced the risk of clinical worsening events in adults with PAH.
Pulmonary arterial hypertension (搜索) (PAH) is a rare, progressive, and life-threatening disorder characterized by the constriction of small pulmonary arteries, leading to elevated blood pressure in the pulmonary circulation. Approximately 40,000 people in the U.S. are living with PAH, with a five-year mortality rate of approximately 43%.