Merck continues to build the case for the pulmonary arterial hypertension drug that won FDA approval in 2024.
In high-risk patients with pulmonary arterial hypertension, Merck’s fusion protein therapeutic Winrevair reduced the likelihood of major morbidity and mortality by 76% in the Phase III ZENITH trial.
Analysts at Guggenheim Partners called this outcome “striking” and “very impressive” in a note to investors Monday, pointing to improvements in key secondary outcomes in overall survival and transplant-free survival.
The Guggenheim analysts also pointed out that Winrevair had “relatively consistent improvements” in mortality and morbidity across patient subgroups, including age, sex and disease subtype and severity.
In November 2024, Merck announced that, following the recommendations of an independent data monitoring board, it was stopping ZENITH ahead of schedule due to “overwhelming efficacy.” On Monday, the pharma revealed that in the Winrevair arm, 17.4% of patients experienced at least one major morbidity or mortality event, as opposed to 34.7% of placebo comparators.
The data were presented at the 2025 American College of Cardiology’s Annual Scientific Session and Expo and simultaneously published in The New England Journal of Medicine.
Winrevair is a recombinant activin receptor type IIA-Fc fusion protein that targets and binds to activin A and other ligands that belong to the TGF-β superfamily. This mechanism of action allows Winrevair to restore balanceto vascular proliferation, a key pathway that is altered in pulmonary arterial hypertension (PAH). In particular, PAH patients see high excessive cell proliferation in key arteries, leading to thickened blood vessel walls and, in turn, impaired blood flow.
Winrevair was approved by the FDA to treat PAH in March 2024, making it the first-ever drug for the disease that targets activin signaling.
Merck continues to build its evidence base for Winrevair. In March 2023, the pharma unveiled full data from the Phase III STELLAR trial, touting a 40.8-meter improvement in 6-minute walk distance in patients with PAH following treatment with the drug. Winrevair also cut the risk of death or clinical worsening by 84% versus placebo.
Merck is also running the Phase III HYPERION study to assess the benefit of Winrevair when used with background therapy. In January 2025, the company ended the trial ahead of schedule, in line with the recommendations of an external committee, because of strong efficacy findings in an interim analysis. Results from HYPERION will be presented later this year, according to Merck’s Monday announcement.
