FDA updates the WINREVAIR label with HYPERION data showing a 76% reduction in clinical worsening risk in newly diagnosed pulmonary arterial hypertension.
Written By: Khushi Patel, PharmD
Reviewed By: Pharmacally Editorial Team
The U.S. Food and Drug Administration (FDA) has approved an update to the U.S. product label for WINREVAIR, adding efficacy and safety findings from HYPERION, a Phase 3 study of adults with WHO Group 1 PAH diagnosed within the previous 12 months.
The trial evaluated patients with WHO functional class (FC) II or III disease who remained at intermediate to high risk of progression despite background PAH therapy. The findings provide clinical evidence for using WINREVAIR within the first year after PAH diagnosis.
WINREVAIR Reduced Clinical Worsening by 76%
HYPERION randomized 320 patients 1:1 to WINREVAIR or placebo, both added to background therapy. WINREVAIR reduced the risk of death or first confirmed morbidity event by 76% compared with placebo (HR 0.24; 95% CI, 0.14–0.41; p<0.0001).
A first clinical worsening event occurred in 10.6% of patients receiving WINREVAIR versus 36.9% receiving placebo. The composite endpoint included all-cause death, unplanned PAH-related hospitalization lasting at least 24 hours, atrial septostomy, lung transplantation, or a decline in 6-minute walk distance accompanied by additional evidence of disease progression.
Participants had been diagnosed with PAH for a mean of 7.2 months. Seventy-two percent were receiving double background therapy, 28% were receiving triple therapy, and 17% were receiving prostacyclin infusion therapy. The treatment effect remained consistent across prespecified subgroups.
HYPERION Stopped Early After ZENITH Results
HYPERION was stopped before its scheduled completion after positive interim results from the ZENITH trial and a review of the totality of evidence from the WINREVAIR clinical development program.
Merck and the study’s external steering committee concluded that the accumulating evidence had resulted in a loss of clinical equipoise, making continued randomization to placebo inappropriate. The decision followed discussion with the FDA and allowed participants the opportunity to receive WINREVAIR through an open-label extension study.
Safety Monitoring Remains Important
Safety findings in HYPERION were generally consistent with those reported in the STELLAR trial. The most common adverse reactions were epistaxis (31.9% with WINREVAIR vs. 6.9% with placebo), telangiectasia (26.3% vs. 11.3%), and increased hemoglobin (11.3% vs. 1.3%). Treatment discontinuation because of an adverse event occurred in 3% of WINREVAIR-treated patients and no placebo-treated patients.
The current prescribing information emphasizes monitoring for erythrocytosis and thrombocytopenia. Hemoglobin and platelet counts should be checked before each dose for the first five doses, or longer if values remain unstable, and periodically thereafter. Treatment should not be initiated when platelet counts are below 50,000/mm³. Severe erythrocytosis can increase the risk of thromboembolic events and hyperviscosity syndrome, while severe thrombocytopenia can increase bleeding risk.
The label also warns about serious bleeding, with greater risk reported in some patients receiving prostacyclin or antithrombotic therapy and in those with low platelet counts.
ERS Guidelines Add to the Clinical Context
The FDA label update comes alongside newly published European Respiratory Society (ERS) guidelines for PAH. The guidelines include WINREVAIR for the first time and provide a strong recommendation for its use in adults receiving background therapy who have not reached low-risk status at follow-up, including patients at intermediate-low, intermediate-high, or high risk.
WINREVAIR Advances Across PAH Risk Groups
HYPERION is the third Phase 3 study of WINREVAIR in PAH. Patients received a target dose of 0.7 mg/kg by subcutaneous injection every three weeks.
WINREVAIR is an activin signaling inhibitor approved for adults with WHO Group 1 PAH to improve exercise capacity and WHO functional class and reduce the risk of clinical worsening events, including PAH hospitalization, lung transplantation, and death. The therapy modulates signaling involved in vascular proliferation and is being evaluated across patients with different levels of disease severity.
Reference
U.S. FDA Approves Update to the Label for WINREVAIR™ (sotatercept-csrk) to Include Data from the Phase 3 HYPERION Trial Evaluating Adults Recently Diagnosed with Pulmonary Arterial Hypertension (PAH, WHO* Group 1 Pulmonary Hypertension), Merck, 22 September 2026
Study of Sotatercept in Newly Diagnosed Intermediate- and High-Risk PAH Participants (MK-7962-005/A011-13) (HYPERION), ClinicalTrials.gov ID NCT04811092
About the Writer
Khushi Patel is a Pharm.D (Linkedin) professional with a strong foundation in clinical pharmacy, patient-centered care, regulatory affairs, and pharmacovigilance, with published work on Brugada syndrome.
Her interests include regulatory affairs, pharmacovigilance, guideline integration, multimodal therapy, pharmacogenomics, and antibiogram utilization, with a focus on evidence-based clinical decision-making and medication safety.
As a Pharmacally healthcare writer, she translates clinical and scientific evidence into clear, accurate, and clinically relevant healthcare content, while continuously developing her expertise in evolving pharmacy practice.