FDA Approves Update for Winrevair Based on Phase 3 HYPERION Trial Data

The FDA approved an update to the US product label for sotatercept-csrk (Winrevair) for injection, 45 mg and 60 mg, based on results from the phase 3 HYPERION (NCT01994772) trial. The update adds efficacy and safety data on adults newly diagnosed with pulmonary arterial hypertension (PAH) who were at intermediate to high risk of disease progression, providing insight into the drug’s use earlier in the treatment course.¹

HYPERION Trial Results Support Earlier Use

HYPERION enrolled 320 adults with PAH, randomizing 160 to Winrevair and 160 to placebo added to background therapy. Adding Winrevair to background therapy reduced the risk of clinical worsening events by 76% compared with placebo (hazard ratio [HR], 0.24; 95% CI, 0.14-0.41; P < .0001).¹

A first clinical worsening event occurred in 10.6% of patients on Winrevair (17 of 160) compared with 36.9% of patients on placebo (59 of 160). The primary composite end point measured time to death or first confirmed morbidity event, including all-cause death, unplanned PAH-related hospitalization of 24 hours or longer, atrial septostomy, lung transplantation, or a decrease in 6-minute walk distance combined with worsening World Health Organization Functional Class, signs of increased right heart failure, or a change in background therapy.¹

Participants enrolled within their first year of diagnosis, with a mean time since diagnosis of 7.2 months. Approximately 72% were on double background therapy, 28% were on triple background therapy, and 17% were on prostacyclin infusion therapy. Merck reported that the treatment effect held consistent across all prespecified subgroups.¹

Updated Safety Information

The label update also adds safety data showing adverse reactions in HYPERION were generally consistent with those seen in STELLAR (NCT04576988). The most common adverse reactions occurring in at least 10% of the Winrevair group and at least 5% more often than placebo were epistaxis (31.9% vs 6.9%), telangiectasia (26.3% vs 11.3%), and increased hemoglobin (11.3% vs 1.3%).¹

No severe reductions in platelet count below 50,000/mm³ occurred in the Winrevair group. Treatment discontinuation due to an adverse event occurred in 3% of the Winrevair group, most often due to epistaxis, compared with 0% of the placebo group.¹

Winrevair carries a contraindication for serious hypersensitivity reactions and warnings for hemoglobin increases that may lead to erythrocytosis, as well as platelet decreases that may lead to thrombocytopenia and bleeding risk. The latter occurs more frequently in patients also on prostacyclin infusion. Treatment should not be initiated if the platelet count is below 50,000/mm³.¹

Building on Prior Phase 3 Evidence

Winrevair, an activin signaling inhibitor, was originally approved by the FDA in March 2024 as the first agency-approved therapy in its class for PAH, based on the phase 3 STELLAR trial. In STELLAR, which enrolled 323 adults, adding sotatercept-csrk to background therapy increased 6-minute walk distance by 41 meters at week 24 and reduced the combined risk of death or PAH clinical worsening events by 84% compared with placebo.²

Matt Gratano, president and CEO of the Pulmonary Hypertension Association, said at the time that “a diagnosis of PAH is a life-changing experience for patients and families.”²

In 2025, the Phase 3 ZENITH trial extended that evidence to patients at high risk of mortality, enrolling 172 adults with WHO FC III or IV disease. At a median follow-up of 10.6 months, the trial’s primary endpoint—a composite of all-cause death, lung transplantation, or hospitalization for PAH—was reduced by 76% with sotatercept compared with placebo, and the trial was stopped early for overwhelming efficacy.³

Eliav Barr, MD, senior vice president, head of global clinical development, and chief medical officer at Merck Research Laboratories, said, “These results led to the ZENITH study being the first PAH clinical trial stopped early.” Full ZENITH results were later published in the New England Journal of Medicine.³

What This Means for Pharmacists

Winrevair is administered subcutaneously once every 3 weeks and, with appropriate training, may be given by patients or caregivers. Pharmacists working with prescribers should be aware of the required hematologic monitoring. Hemoglobin and platelets need to be checked before each of the first 5 doses, or longer if values are unstable, and periodically afterward to guide dose adjustments.¹

Because the HYPERION data extend the evidence base to patients diagnosed within the past year, pharmacists may see the drug used earlier in a patient’s treatment course than before, alongside double or triple background PAH therapy.¹

REFERENCES

1. 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). News release. Merck. September 22, 2026. Accessed September 23, 2026. https://www.merck.com/news/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-hypertensio/

2. Biscaldi L. FDA approves sotatercept-csrk for pulmonary arterial hypertension. Drug Topics. March 27, 2024. Accessed September 23, 2026. https://www.drugtopics.com/view/fda-approves-sotatercept-csrk-for-pulmonary-arterial-hypertension

3. Gallagher A. Sotatercept reduces risk of major morbidity, mortality for pulmonary arterial hypertension. Drug Topics. April 2, 2025. Accessed September 23, 2026. https://www.drugtopics.com/view/sotatercept-reduces-risk-of-major-morbidity-mortality-for-pulmonary-arterial-hypertension