FDA Updates Sotatercept Label, ERS Releases PAH Guidelines Based on HYPERION Data

On September 22, 2026, the US Food and Drug Administration (FDA) announced an update to the label of sotatercept-csrk (WINREVAIR) for pulmonary arterial hypertension (PAH) to include data from the phase 3 HYPERION trial.¹

Sotatercept, an activin signaling inhibitor, received FDA approval for patients with World Health Organization (WHO) Group 1 PAH to improve exercise capacity and WHO functional class (FC), as well as reducing the risk of clinical worsening events. The present update expands sotatercept’s indication to patients newly diagnosed with WHO FC 2 or 3 at intermediate to high risk of disease progression.¹

Additionally, the European Respiratory Society (ERS) recently published clinical guidelines for PAH, which are the first to include sotatercept. The update was specifically prompted by sotatercept’s current body of evidence, based on results from the HYPERION trial.¹

“I think HYPERION clearly supports earlier addition of sotatercept for patients in this population,” Aaron Waxman, MD, PhD, executive director of the Center for Pulmonary Heart Diseases at Brigham and Women’s Hospital and the lead investigator in HYPERION, told HCPLive in an exclusive interview. “It really shifts the clinical emphasis from waiting for obvious deterioration to being proactive and reducing the near-term morbidity during a period when pulmonary vascular disease may still be more modifiable.”

HYPERION was a phase 3, randomized, double-blind, placebo-controlled study evaluating sotatercept on top of background therapy in newly diagnosed patients with PAH at intermediate or high risk of progression. Patients who had symptomatic WHO FC 2 or 3 PAH, were diagnosed within 12 months of screening, and were on stable doses of a double or triple combination of background PAH therapies and diuretics for ≥90 days, among other criteria, were eligible for enrollment. Those with pulmonary hypertension WHO groups 2, 3, 4, or 5, or uncontrolled systemic hypertension based on sitting blood pressure, were excluded.^2,3

Following enrollment, patients were randomly assigned to either add-on therapy with subcutaneous sotatercept or placebo every 21 days. The primary endpoint was clinical worsening, which was a composite of death from any cause, unplanned hospitalization for worsening of PAH, atrial septostomy, lung transplantation, or deterioration in performance in exercise tests.²

HYPERION was stopped early due to loss of clinical equipoise after the reporting of positive results from prior sotatercept trials. A total of 320 patients were included, with 160 assigned to each treatment group. Investigators followed up with these patients for a median of 13.2 months; in this time, ≥1 primary endpoint event occurred in 17 patients (10.6%) in the sotatercept group and in 59 patients (36.9%) in the placebo group (HR, 0.24; 95% CI, 0.14-0.41; P <.001).²

Deterioration in exercise testing occurred in 8 patients (5%) in the sotatercept group and 46 (28.8%) in the placebo arm, while unplanned hospitalization occurred in 3 patients (1.9%) and 14 patients (8.8%), respectively. All-cause mortality occurred in 7 patients (4.4%) and 6 patients (3.8%), respectively. No cases of atrial septostomy or lung transplantation occurred during the trial.²

While HYPERION was terminated early, the results were enough to facilitate the ERS guideline update and the new label for sotatercept. However, patients with PAH at low risk of disease progression still do not have an indication for sotatercept, and Waxman believes that HYPERION does not sufficiently answer this question.

“I think, for now, a defensible, practical approach is to use it early,” Waxman said. “Do repeated risk assessment after initial combination therapy. And any patient who fails to achieve or maintain a low risk profile should really prompt the consideration of sotatercept rather than a prolonged period of observation and trying to figure out what to do next.”

Editors’ Note: Waxman reports disclosures with Acceleron, Aria CV, Pharmosa, and United Therapeutics.

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 (PAH, WHO Group 1 Pulmonary Hypertension). September 22, 2026. Accessed October 5, 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. Sotatercept for pulmonary arterial hypertension within the first year after diagnosis. New England Journal of Medicine. 2025;393(16):1599-1611. doi:10.1056/nejmoa2508170

3. Acceleron Pharma. Study of Sotatercept in Newly Diagnosed Intermediate- and High-Risk PAH Participants (MK-7962-005/A011-13) (HYPERION). ClinicalTrials.gov Identifier: NCT04811092. Updated June 8, 2026. Accessed October 5, 2026. https://clinicaltrials.gov/study/NCT04811092