FDA Approves Sotatercept-csrk Label Update for Newly Diagnosed PAH

The FDA has approved an update to the US prescribing information for sotatercept-csrk (WINREVAIR; Merck) incorporating results from the phase 3 HYPERION trial, in which adding the therapy to background treatment reduced the risk of clinical worsening by 76% among adults diagnosed with pulmonary arterial hypertension (PAH) within the previous year.¹

Clinical worsening occurred in 10.6% of participants receiving sotatercept-csrk and 36.9% receiving placebo over a median follow-up of 13.2 months (hazard ratio [HR], 0.24; 95% CI, 0.14-0.41; P<.001).¹˒²

The regulatory action updates the label with efficacy and safety findings from HYPERION; it does not represent a new indication. Sotatercept-csrk was previously approved for adults with PAH—World Health Organization (WHO) group 1 pulmonary hypertension—to improve exercise capacity and WHO functional class and reduce the risk of clinical worsening events, including PAH-related hospitalization, lung transplantation, and death.¹

The revised label provides additional evidence supporting the use of sotatercept-csrk earlier in the PAH treatment course, including among patients already receiving multidrug background therapy.

HYPERION Evaluated Treatment Within First Year of Diagnosis

HYPERION was a global, double-blind, placebo-controlled trial involving 320 adults with WHO functional class II or III PAH diagnosed within 12 months of screening. Participants were at intermediate to high risk of disease progression and were randomly assigned 1:1 to subcutaneous sotatercept-csrk or placebo every 3 weeks in addition to background PAH therapy.¹˒²

Sotatercept-csrk was initiated at 0.3 mg/kg and increased to a target dose of 0.7 mg/kg.

Participants had a median age of 60 years, with an age range of 18 to 88 years, and the mean time since PAH diagnosis was 7.2 months. Overall, 79% had WHO functional class III disease and 21% had functional class II disease. Idiopathic PAH accounted for 59% of cases, and connective tissue disease-associated PAH accounted for 30%.¹

At baseline, 72% of participants were receiving double background therapy and 28% were receiving triple therapy; 17% were receiving prostacyclin infusion therapy.

The primary end point was time to death or a first confirmed morbidity event. Qualifying events included all-cause death, an unplanned PAH-related hospitalization lasting at least 24 hours, atrial septostomy, lung transplantation, or a decrease in 6-minute walk distance accompanied by worsening functional class, signs or symptoms of increased right heart failure, or a change in background PAH therapy.¹

Deterioration in exercise performance related to PAH occurred in 5.0% of participants receiving sotatercept-csrk and 28.8% receiving placebo. Unplanned hospitalization for worsening PAH occurred in 1.9% and 8.8%, respectively. All-cause mortality was similar between the groups, occurring in 4.4% of the sotatercept-csrk group and 3.8% of the placebo group. No participants underwent atrial septostomy or lung transplantation.²

The trial was stopped early after positive findings from the separate ZENITH trial and a review of the totality of evidence from the sotatercept-csrk clinical development program led investigators to conclude that clinical equipoise had been lost.¹˒²

“The results of HYPERION provide evidence for the use of WINREVAIR in adults diagnosed with PAH within the previous year,” Vallerie McLaughlin, MD, director of the Pulmonary Hypertension Program at the University of Michigan, said in the announcement.¹

Safety Information Added to Label

The adverse-event profile in HYPERION was generally consistent with findings from the phase 3 STELLAR trial. The most common adverse reactions occurring in at least 10% of sotatercept-csrk-treated participants and at least 5 percentage points more frequently than with placebo were epistaxis (31.9% vs 6.9%), telangiectasia (26.3% vs 11.3%), and increased hemoglobin (11.3% vs 1.3%).¹

Treatment discontinuation because of an adverse event occurred in 3% of the sotatercept-csrk group and no participants receiving placebo. Epistaxis was the most common reason for discontinuation.

Serious bleeding occurred in 4% of participants receiving sotatercept-csrk and 2% receiving placebo in HYPERION. The updated safety information also notes postmarketing reports of gastrointestinal bleeding associated with angiodysplasias. Endoscopic evaluation should be considered for recurrent or unexplained gastrointestinal bleeding, according to the prescribing information.¹

Clinicians should measure hemoglobin and platelet levels before each of the first 5 doses—or longer if values remain unstable—and periodically thereafter. Sotatercept-csrk can cause erythrocytosis and thrombocytopenia, and treatment should not be initiated when the platelet count is below 50,000/mm³. The medication is contraindicated in patients with serious hypersensitivity to sotatercept-csrk or its excipients.¹

For primary care clinicians, the label update does not change the need for specialist-directed PAH treatment, but it reinforces the importance of timely recognition and referral. Unexplained exertional dyspnea, fatigue, syncope, chest discomfort, or signs of right-sided heart failure may warrant evaluation for pulmonary hypertension, particularly when symptoms remain unexplained after initial cardiac and pulmonary assessment.

References

1. Merck. US 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. News release. September 22, 2026. Accessed September 22, 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. McLaughlin VV, Hoeper MM, Badesch DB, et al; HYPERION Trial Investigators. Sotatercept for pulmonary arterial hypertension within the first year after diagnosis. N Engl J Med. 2025;393(16):1599-1611. doi:10.1056/NEJMoa2508170