Early Winrevair trial end to allow all patients to start active treatment
HYPERION participants can now receive PAH therapy in another study
Merck announced that its Phase 3 clinical trial HYPERION, which had been testing Winrevair (sotatercept-csrk) in people with recently diagnosed pulmonary arterial hypertension (PAH), will be ended early — a move that will allow all study participants, including those who had been assigned to receive a placebo, to be given active treatment with the PAH therapy.
The participants in HYPERION (NCT04811092) can now all choose to be treated with Winrevair as part of the open-label extension study SOTERIA (NCT04796337), according to the developer.
The decision to end the trial early was based on new positive data from another Phase 3 trial of Winrevair — early results that Merck said made continuing HYPERION unnecessary, and also not helpful for its participants.
“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,” Eliav Barr, MD, chief medical officer, senior vice president and head of global clinical development at Merck Research Laboratories, said in a company press release.
Barr expressed the company’s thanks to “the dedicated community of patients who participated in these studies” and noted that Merck is “pleased to offer the option of receiving Winrevair through the Phase 3 SOTERIA … study.” SOTERIA is ongoing at 189 locations worldwide, and is expected to enroll an estimated 700 participants.
All of the HYPERION participants are in functional class 2 or 3, as set by the World Health Organization, and have an intermediate or high risk of disease progression, the company noted.
For some in HYPERION, it will now be active treatment instead of placebo
Merck’s decision to pull the plug on HYPERION followed positive data from the ZENITH clinical trial (NCT04896008). That study, launched in 2021, was testing Winrevair against a placebo, on top of background therapy, in people with PAH.
According to the company, results from ZENITH showed that Winrevair significantly reduced mortality risk among PAH patients at high risk of dying. That trial was also stopped early to allow all patients to access the drug.
After reviewing data from ZENITH and other studies of Winrevair, Merck and the trial’s steering committee decided that continuing HYPERION would not be ethically justifiable, given that some patients would be getting the placebo instead of the active treatment.
“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 [a] placebo on top of background therapy, has lost clinical equipoise and should be stopped early,” said Vallerie McLaughlin, MD, an investigator on both the HYPERION and ZENITH studies and a professor at the University of Michigan in Ann Arbor. Equipoise means that investigators have true uncertainty about a therapy’s merits.
In PAH, the cells that line the inside of blood vessels, called endothelial cells, grow abnormally, narrowing vessels and leading to abnormally high blood pressure in the vessels that carry blood through the lungs. Winrevair, given every three weeks by subcutaneous or under-the-skin injection, works to block molecular signals that drive the abnormal growth of endothelial cells.
Winrevair is approved to treat adults with PAH in the U.S. and Canada, and in the European Union.
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 … has lost clinical equipoise and should be stopped early.
Merck noted that it has discussed the decision to stop HYPERION early with the U.S. Food and Drug Administration. The company said it plans to present details on the results from the study later this year.
Noting that PAH is “a progressive and debilitating disease with a high incidence of morbidity and mortality,” McLaughlin said investigators “look forward to continuing to evaluate these patients and any potential impact to the treatment landscape as a result of these data.”
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