FDA

FDA OKs updated indication for Winrevair in PAH

October 31, 2025

On October 27, 2025, FDA approved an update to the U.S. product label for Winrevair (sotatercept-csrk) for injection. Winrevair, an activin signaling inhibitor, is now approved for the treatment of adults with pulmonary arterial hypertension (PAH, WHO Group 1) to improve exercise capacity and WHO functional class (FC), and reduce the risk of clinical worsening events, including hospitalization for PAH, lung transplantation, and death.

This approval expands the indication of Winrevair to include components of the clinical worsening events: hospitalization for PAH, lung transplantation, and death.

Efficacy

Approval of the expanded indication was based on data from the ZENITH trial (NCT04896008; N=172; 86 WINREVAIR, 86 placebo), in which the primary efficacy endpoint was time to first event of all-cause death, lung transplantation, or PAH worsening-related hospitalization of ≥24 hours. In the Winrevair group, the risk of a first event was 76% lower compared with the placebo group (hazard ratio [HR], 0.24; 95% confidence interval, 0.13-0.43; p<0.0001). Fewer participants in the WINREVAIR group (17%) than in the placebo group (55%) had a primary endpoint event as of the data cutoff. Based on the primary endpoint result, the study was stopped for favorable efficacy at the interim analysis.

The secondary endpoint of overall survival (OS) included all deaths up to the data cutoff, except for those occurring after lung transplantation or enrollment in a long-term follow-up study. Twenty OS events were observed (7 deaths in the Winrevair group and 13 deaths in the placebo group). The point estimate for the OS HR favored the Winrevair group.

Safety

The most common adverse reactions (≥10% for Winrevair and at least 5% more than placebo) in the ZENITH trial were:

• infections: 67.4% vs. 44.2%
• epistaxis: 45.3% vs. 9.3%
• diarrhea: 25.6% vs. 17.4%
• telangiectasia: 25.6% vs. 3.5%
• increased hemoglobin: 15.1% vs. 1.2%
• rash: 10.5% vs. 4.7%
• erythema: 10.5% vs. 3.5%
• gingival bleeding: 10.5% vs. 2.3%

Median duration of exposure was longer in the Winrevair group (435 days) vs. the placebo group (268 days). In the Winrevair group, 1 patient (1%) discontinued study intervention due to an adverse event, vs. 4 patients (5%) in the placebo group.

Sources:

US FDA approves updated indication for Winrevair™ (sotatercept-csrk) in adults with pulmonary arterial hypertension (PAH, WHO* Group 1 pulmonary hypertension) based on phase 3 ZENITH study. [News release]. 2025. https://www.merck.com/news/u-s-fda-approves-updated-indication-for-winrevair-sotatercept-csrk-in-adults-with-pulmonary-arterial-hypertension-pah-who-group-1-pulmonary-hypertension-based-on-phase-3-zenith-study/

Winrevair (sotatercept-csrk) [package insert]. Merck. https://www.merck.com/product/usa/pi_circulars/w/winrevair/winrevair_pi.pdf Revised October 2025. Accessed October 30, 2025.