FDA Adds HYPERION Data to Sotatercept-csrk Label for Early PAH

Adding sotatercept-csrk (Winrevair; Merck) to background therapy cut the risk of clinical worsening events by 76% in adults recently diagnosed with pulmonary arterial hypertension (PAH), according to new data added to the drug's FDA label.

HYPERION Results Support Earlier Use

HYPERION (NCT04811092) randomized 320 adults with newly diagnosed PAH (WHO functional class II or III, diagnosed within 12 months of screening) at intermediate to high risk of disease progression to Winrevair or placebo, both added to background therapy, in a 1:1 ratio. Participants had a mean time since diagnosis of 7.2 months; 72% were on double background therapy and 28% on triple therapy, with 17% also receiving prostacyclin infusion.¹

Adding sotatercept-csrk reduced the risk of clinical worsening events by 76% compared with placebo (HR, 0.24; 95% CI, 0.14-0.41; P < .0001). A first clinical worsening event—defined as death or a confirmed morbidity event such as PAH-related hospitalization, atrial septostomy, or lung transplantation—occurred in 10.6% (17 of 160) of patients on Winrevair versus 36.9% (59 of 160) on placebo.¹ HYPERION is the third phase 3 trial of Winrevair in PAH to inform the product label, following STELLAR and ZENITH.²

“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,” said Vallerie McLaughlin, MD, director of the Pulmonary Hypertension Program at the University of Michigan and an investigator on the trial, in a statement.¹

Updated Safety Guidance

The most common adverse reactions occurring in at least 10% of patients treated with sotatercept-csrk 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%). No severe reductions in platelet count below 50,000/mm³ occurred in the sotatercept-crsk group, and treatment discontinuation due to an adverse event occurred in 3% of patients treated with sotatercept-crsk, most often for epistaxis, vs none on placebo.

Because sotatercept-crsk can raise hemoglobin and lower platelet counts, the label calls for monitoring both before each of the first 5 doses, or longer if values are unstable, and periodically thereafter; treatment should not begin if platelet count is below 50,000/mm³. Sotatercept-crsk remains contraindicated in patients with serious hypersensitivity to the drug or its excipients.

ERS Guidelines Recognize Winrevair

The update follows new PAH clinical guidelines published this month by the European Respiratory Society (ERS), the first formal guidelines to include Winrevair. The guidelines give Winrevair a “strong” recommendation, with “high” certainty of evidence, for adults with PAH on background therapy who have not reached low-risk status—making it the only add-on PAH therapy to receive that designation.^1,2

“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 Joerg Koglin, MD, senior vice president and head of general and specialty medicine, global clinical development at Merck Research Laboratories, in a statement.¹

References

1. 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. Merck. Published 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. Campbell P. FDA updates sotatercept label with HYPERION data in early PAH. HCPLive^®. Published September 22, 2026. Accessed September 22, 2026. https://www.hcplive.com/view/fda-updates-sotatercept-label-with-hyperion-data-in-early-pah