FDA Expands Winrevair Label With HYPERION Data in Recently Diagnosed PAH

The FDA has approved an update to the US product label for Winrevair (sotatercept-csrk), 45 mg and 60 mg, incorporating efficacy and safety data from the Phase 3 HYPERION trial.¹ Winrevair, an activin signaling inhibitor, was already approved for adults with pulmonary arterial hypertension (PAH, WHO Group 1) to improve exercise capacity and WHO functional class and to reduce clinical worsening events, including hospitalization, lung transplantation, and death.¹ The label update adds data specific to adults newly diagnosed with PAH — WHO functional class II or III, diagnosed within 12 months of study screening — at intermediate to high risk of disease progression, providing evidence for using Winrevair earlier in the treatment course.¹

What did the HYPERION trial show?

In HYPERION (N=320; 160 Winrevair, 160 placebo), adding Winrevair to background therapy reduced the risk of clinical worsening events by 76% compared to placebo (hazard ratio 0.24; 95% CI, 0.14 to 0.41; p<0.0001).¹ A first clinical worsening event occurred in 10.6% of patients (17 of 160) on Winrevair versus 36.9% of patients (59 of 160) on placebo.¹ The primary composite endpoint measured time to death or first confirmed morbidity event, including all-cause death, unplanned PAH-related hospitalization of at least 24 hours, atrial septostomy, lung transplantation, or a decrease in six-minute walk distance combined with worsening functional class, signs of right heart failure, or a change in background therapy.¹ The treatment effect was consistent across all prespecified subgroups, including age, sex, PAH subtype, background therapy regimen, and baseline risk score.¹

Who was studied in HYPERION?

Participants were enrolled a mean of 7.2 months after PAH diagnosis; 72% were on double background therapy and 28% on triple background therapy, with 17% on prostacyclin infusion therapy.¹ Median age was 60 years (range 18 to 88), and idiopathic PAH (59%) and PAH associated with connective tissue disease (30%) were the most common etiologies.¹ Most participants (79%) were WHO functional class III at baseline.¹ HYPERION was stopped early based on positive interim results from the Phase 3 ZENITH trial — a separate Phase 3 study in patients at high risk of mortality — and a review of the totality of Winrevair clinical data.¹

"The HYPERION study included people with PAH who closely reflect those we see in everyday clinical practice, including individuals who were recently diagnosed, older adults and people managing other health conditions," said Dr. Vallerie McLaughlin, Kim A Eagle MD Endowed Professor of Cardiovascular Medicine and director, Pulmonary Hypertension Program, University of Michigan in Ann Arbor. "The results of HYPERION provide evidence for the use of WINREVAIR in adults diagnosed with PAH within the previous year who were receiving background therapy."¹

What new safety information was added?

The updated label adds a contraindication for serious hypersensitivity reactions, including anaphylaxis and angioedema.¹ Winrevair carries existing warnings for erythrocytosis and severe thrombocytopenia, requiring hemoglobin and platelet monitoring before each of the first five doses; treatment should not be initiated if platelet count is below 50,000/mm³.¹ Serious bleeding was reported in 4% of Winrevair patients versus 2% of placebo patients in HYPERION, consistent with rates observed in the earlier STELLAR trial (4% versus 1%) and the ZENITH trial (7% versus 5%).¹ No severe platelet reductions below 50,000/mm³ occurred in the HYPERION Winrevair group.¹ The most common adverse reactions in HYPERION (occurring in at least 10% of Winrevair patients and at least 5% more than placebo) were epistaxis (31.9% versus 6.9%), telangiectasia (26.3% versus 11.3%), and increased hemoglobin (11.3% versus 1.3%).¹ Treatment discontinuation due to an adverse event occurred in 3% of the Winrevair group versus none in the placebo group, most commonly due to epistaxis.¹

What do new clinical guidelines say?

Earlier this month, the European Respiratory Society published updated PAH clinical guidelines — the first formal clinical guidelines to include Winrevair.¹ The guidelines give a "strong" recommendation, graded with "high" certainty of evidence, for using Winrevair in adult PAH patients on background therapy who have not reached low-risk status at follow-up, making it the only add-on PAH therapy to receive a strong recommendation in the guidelines.¹ Winrevair was previously approved in the EU based on the STELLAR trial, becoming the first activin signaling inhibitor authorized across the EU's 27 member states.²

"HYPERION is the third Phase 3 study of WINREVAIR in PAH and provides robust clinical evidence in adults with PAH when added to background therapy, including within the first year following a diagnosis," said Dr. Joerg Koglin, senior vice president, head of general and specialty medicine, global clinical development, Merck Research Laboratories.¹

PAH remains a rare disease, with US prevalence estimated at roughly 1.06 cases per 100,000 people; before targeted therapies existed, the five-year survival rate after diagnosis was just 34%.³

References

1. Merck. 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. Press release. Published September 22, 2026. Accessed September 23, 2026.
2. Merck. Merck Receives European Commission Approval for Winrevair (sotatercept) in Combination with Other Pulmonary Arterial Hypertension (PAH) Therapies, for the Treatment of PAH in Adult Patients with Functional Class II-III. Press release. Published August 26, 2024. Accessed September 23, 2026.
3. Liu L, Li C, Cai J, et al. Trends and levels of the global, regional, and national burden of pulmonary arterial hypertension from 1990 to 2021: findings from the Global Burden of Disease study 2021. Front Med (Lausanne). 2024. doi:10.3389/fmed.2024.1515961