With efficacy assured, Merck halts another trial of blockbuster-to-be Winrevair

 Merck has halted the phase 3 HYPERION trial of its pulmonary arterial hypertension (PAH) treatment Winrevair after reviewing positive interim results from another study and evaluating the drug’s overall clinical program.

The decision comes after Merck revealed in November that the phase 3 ZENITH trial had met its primary endpoint. Based on strong efficacy results, an independent data monitoring committee had urged Merck to stop ZENITH early and offer Winrevair to all 172 patients in the study.

Two months later, Merck and the Winrevair program’s steering committee have agreed to take that action with the HYPERION trial. The roughly 300 participants in HYPERION will be offered access to Winrevair, Merck said on Thursday.

“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, Merck’s head of global clinical development and chief medical officer, said in a release.

The steering committee unanimously agreed that the HYPERION study had lost its “clinical equipoise,” committee member Vallerie McLaughlin, M.D., who also serves as an investigator in the ZENITH and HYPERION trials, added in the release. 

When a trial loses its "clinical equipoise" it has become unbalanced in the eyes of investigators, who believe that the treatment supplied in one arm is demonstrably superior to that in another arm. When this is the case, is unethical to continue to provide patients with the inferior therapy.

Findings from the HYPERION trial will be presented at a future medical meeting, Merck said.

The trial was evaluating Winrevair in combination with background PAH therapy versus placebo and background PAH therapy in newly diagnosed patients with an intermediate (Functional Class II) or high (FC III) risk of disease progression. The primary endpoint measured patients' time to clinical worsening (TTCW) as measured by their first confirmed morbidity or mortality event. 

In the ZENITH trial, with the same primary outcome measure, Winrevair met its primary endpoint by extending the time to patients' first morbidity or mortality event—a range of outcomes including all-cause death, lung transplantation, or hospitalization for at least 24 hours linked to disease worsening. The drug also helped reduce the risk of morbidity or mortality versus placebo.

The difference between the HYPERION and ZENITH trials was their patient populations, as the latter included those in the FC III and IV disease.

Merck has high hopes for Winrevair to be among the portfolio of assets that will blossom as the company loses patent protection for cancer superstar Keytruda later this decade.

Merck gained Winrevair in its $11.5 billion acquisition of Acceleron in 2021 and got it across the FDA finish line in March of 2024 based on results from the phase 3 STELLAR trial. That study compared Winrevair to placebo as an add-on to background therapy with exercise capacity as the primary endpoint.

Winrevair garnered slightly disappointing sales of $149 million in the third quarter of 2024 but a recent survey by Leerink Partners of cardiologists and pulmonologists indicates that it is primed to have strong uptake this year. The company has projected peak sales of $3 billion for the medicine. 

https://www.fiercepharma.com/pharma/efficacy-assured-merck-halts-trial-blockbuster-be-winrevair