Results from a Phase 3 clinical study of adults with pulmonary arterial hypertension found Winrevair reduced the risk of clinical worsening events by 76%.


RT’s Three Key Takeaways:

  1. Winrevair reduced risk — In the Phase 3 HYPERION trial, Winrevair lowered the risk of clinical worsening events by 76% compared with placebo in recently diagnosed adults with pulmonary arterial hypertension (PAH).
  2. Early and consistent benefit — Treatment effects were observed within six weeks, with benefits sustained across all prespecified subgroups, including idiopathic PAH, connective tissue disease, and patients on double or triple background therapy.
  3. Favorable safety and secondary outcomes — Winrevair showed a safety profile consistent with prior trials and delivered statistically significant improvements in multicomponent outcomes and maintenance of low risk scores.


Results from a Phase 3 clinical study of adults with pulmonary arterial hypertension found Winrevair reduced the risk of clinical worsening events by 76%, according to Merck data presented at ERS 2025 and published in NEJM.

Merck’s Phase 3 HYPERION trial evaluated Winreviar (sotatercept-csrk) versus placebo (both in combination with background therapy) in recently diagnosed adults with pulmonary arterial hypertension (PAH, WHO Group 1) functional class (FC) II or III at intermediate or high risk of disease progression, as measured by a composite endpoint of all-cause death, the need for non-planned PAH-related hospitalization ≥24 hours, atrial septostomy, lung transplantation or PAH deterioration.

HYPERION included participants who were within their first year of diagnosis (median seven months and as early as one month), with over 70% of trial participants on double background therapy. In the pivotal Phase 3 study, STELLAR, participants were WHO Group 1, FC II or III at baseline and had an average disease duration of 8.8 years from PAH diagnosis to screening. The safety profile of Winrevair was generally consistent with that observed in previous trials.

In HYPERION, there was an early and sustained separation in the Kaplan-Meier curves with treatment benefit observed within six weeks of randomization. Patients on placebo plus background standard of care therapy experienced accumulation of clinical worsening events. Results showed that 10.6% (n=17/160) of patients treated with Winrevair compared to 36.9% (n=59/160) in the placebo group experienced at least one clinical worsening event. The treatment effect was consistent across all prespecified subgroups treated with Winrevair, including patients with idiopathic PAH, those with connective tissue disease, those on double background therapy, those on triple background therapy and those at intermediate or intermediate-low risk by REVEAL Lite 2 and COMPERA 2.0 risk tools, respectively.

“PAH is a rare condition that can progress quickly making diagnosis and early treatment critically important,” said Dr. Vallerie McLaughlin,2 Kim A Eagle MD Endowed Professor of Cardiovascular Medicine and Director, Pulmonary Hypertension Program, University of Michigan in Ann Arbor. “The patients with PAH enrolled in HYPERION were early in their treatment journey, had co-morbidities and were older, which reflects the type of patients we are diagnosing in a contemporary real-world setting. I am encouraged by the compelling results of the HYPERION study demonstrating that initiation of Winrevair on top of background therapy within the first year of diagnosis significantly reduces the risk of clinical worsening events compared to placebo.”

“These positive results from HYPERION expand on the body of clinical evidence for Winrevair, now including PAH patients within their first year of diagnosis, including those earlier in their treatment journey,” said Dr. Joerg Koglin, senior vice president, head of general and specialty medicine, global clinical development, Merck Research Laboratories. “The totality of Winrevair data to date continues to reinforce our confidence in its practice-changing potential. We thank the study participants and investigators for their contributions to this important study.”

The safety profile of Winrevair in HYPERION was generally consistent with that observed in previous studies. The median duration of follow-up was longer in those receiving Winrevair (14.6 months) compared with those receiving placebo (11.5 months). Adverse events occurred in 89.4% versus 90.0% and serious adverse events in 24.4% versus 28.1% of participants in the Winrevair and placebo groups, respectively.

Winrevair demonstrated statistically significant improvements in two secondary endpoints, including multicomponent improvement and maintenance or achievement of a low REVEAL Lite 2 score. Results showed that 29.4% of patients treated with Winrevair met all three criteria of multicomponent improvement (improvement in 6MWD, improvement or maintenance/achievement of NT-proBNP, and improvement in WHO FC or maintenance of WHO FC II) versus 14.6% treated with placebo. An additional secondary endpoint demonstrated 60.1% of patients treated with WINREVAIR maintained or achieved a low REVEAL LITE 2 score (≤5) relative to baseline at Week 24 compared to 47.9% treated with placebo. WINREVAIR did not show statistical significance in achieving or maintaining low risk for a simplified French risk score (SFRS). Subsequent secondary endpoints showed numerical improvements in the WINREVAIR arm (including NT-proBNP, WHO class and 6MWD), but were not formally tested due to the prespecified hierarchical testing strategy.

Earlier this year, the HYPERION trial was stopped early based on a review of the totality of data from the Winrevair clinical program at that time, and all patients were offered the opportunity to receive Winrevair through the SOTERIA open-label extension study. HYPERION is the third Phase 3 study of WINREVAIR to demonstrate significant efficacy in adults with PAH. The first was the Phase 3 STELLAR study previously presented at ACC.23, followed by the Phase 3 ZENITH study presented at ACC.25. Results from HYPERION will be submitted to regulatory authorities around the world. Winrevair is currently approved in more than 54 countries based on the results from the STELLAR study.

  1. Dr. McLaughlin is a member of the adult sotatercept steering committee, an investigator in the ZENITH and HYPERION studies and a paid consultant to Merck.