Merck's Winrevair Shows Unprecedented Efficacy in Pulmonary Arterial Hypertension Treatment

Merck's pulmonary arterial hypertension (PAH) drug Winrevair has demonstrated remarkable efficacy in a recent phase 3 trial, potentially revolutionizing treatment for this rare and life-threatening condition. The interim results of the Zenith study were so compelling that Merck not only halted this trial but also terminated another ongoing study of the first-in-class activin signaling inhibitor.

Zenith Trial Results Showcase Winrevair's Potential

The Zenith trial, which included 172 patients at the highest risk of mortality (World Health Organization Functional Class III or IV), achieved its primary endpoint of time to clinical worsening to first morbidity or mortality event. Winrevair, when added to maximum background therapy, reduced the risk of all-cause death, lung transplantation, and hospitalization by an impressive 76% compared to placebo.

Dr. Joerg Koglin, Merck's head of general medicine, global clinical development, emphasized the significance of these results: "I've been doing clinical research for almost 30 years and have never seen a study with a hard-outcome endpoint with this effect size."

Key findings from the Zenith trial include:

• 17% of Winrevair patients experienced one or more major morbidity or mortality events, compared to 55% in the placebo arm.
• 7 deaths (8%) occurred in the Winrevair arm versus 13 (15%) in the placebo arm.
• Only 1 Winrevair patient (1%) required a lung transplant, compared to 6 (7%) in the placebo group.
• PAH hospitalizations were significantly reduced: 8 patients (9%) on Winrevair versus 43 patients (50%) on placebo.

Expanding Winrevair's Reach and Market Potential

Winrevair, initially developed by Acceleron and Celgene, was acquired by Merck through its $11.5 billion buyout of Acceleron in 2021. The drug has already been approved in more than 40 countries, including the United States, based on the earlier Stellar phase 3 study.

The pharmaceutical industry is taking notice of Winrevair's potential. Analysts from Citi have increased their 2025 sales projection from $1.3 billion to $1.5 billion and raised their 2030 peak sales estimate from $5.7 billion to $6.1 billion. This positions Winrevair as a strong competitor in the PAH market, currently dominated by Johnson & Johnson's Opsumit and Uptravi, which had combined sales of $4 billion in 2024.

Merck reported 2024 sales of Winrevair at $419 million, with nearly half of that ($200 million) coming in the fourth quarter alone, indicating rapid market adoption and growth potential.

Implications for PAH Treatment and Future Research

PAH is a rare, rapidly progressing disease affecting approximately 40,000 people in the United States. It disproportionately affects women and middle-aged individuals, with nearly half of patients dying within five years of diagnosis.

Winrevair's mechanism of action sets it apart from existing PAH treatments. While current therapies like J&J's Opsumit and Uptravi focus on symptom management by dilating blood vessels, Winrevair targets the underlying cause of PAH by rebalancing cell signaling.

The success of the Zenith trial has led Merck to halt its Hyperion study, which focused on newly diagnosed PAH patients. Dr. Eliav Barr, Merck's chief medical officer, stated that it would be unethical to continue giving patients placebo when Winrevair's superiority has been clearly established. All 300 patients from both the Zenith and Hyperion trials have been offered to receive Winrevair through the Soteria open-label extension study.

As the pharmaceutical industry continues to watch Winrevair's progress, these latest results suggest a potential paradigm shift in PAH treatment, offering new hope for patients facing this challenging condition.