FDA Approves Sotatercept-csrk Label Update for Early PAH Use

The FDA has approved a label update for sotatercept-csrk (Winrevair; Merck) that adds data from the phase 3 HYPERION trial (NCT04811092), giving pharmacists new evidence for starting the activin signaling inhibitor earlier in a patient's pulmonary arterial hypertension (PAH, World Health Organization [WHO] Group 1 pulmonary hypertension) treatment course.^1,2

In HYPERION, adding sotatercept to background therapy within the first year of a PAH diagnosis reduced the risk of clinical worsening events by approximately 76% compared with placebo—a finding that shifts the clinical conversation from whether to prescribe the drug toward when to start it.^1,3

What HYPERION Tested

HYPERION enrolled 320 adults with newly diagnosed PAH (WHO functional class [FC] II or III, diagnosed within 12 months of screening) at intermediate to high risk of disease progression and randomly assigned them to subcutaneous sotatercept (target dose 0.7 mg/kg) or placebo every 3 weeks on top of background therapy. Participants were a mean of 7.2 months from diagnosis; 72% were on double background therapy and 28% on triple therapy, with 17% also receiving prostacyclin infusion. The primary composite end point—time to death or first confirmed morbidity event—included all-cause death, unplanned PAH-related hospitalization of at least 24 hours, atrial septostomy, lung transplantation, or a drop in 6-minute walk distance combined with worsening FC, signs of right heart failure, or a change in background therapy.^1,3

A first clinical worsening event occurred in 10.6% of patients (17 of 160) who received sotatercept versus 36.9% (59 of 160) who received placebo (HR, 0.24; 95% CI, 0.14-0.41). The trial was stopped early after positive interim results from the phase 3 ZENITH trial (NCT04896008) removed clinical equipoise for continuing to randomize patients to placebo.^1,3

What the Label Update Adds

Beyond the efficacy data, the update adds safety information specific to this earlier-diagnosis population. The most common adverse events (AEs) in HYPERION were epistaxis (31.9% vs 6.9% with placebo), telangiectasia (26% vs 11%), and increased hemoglobin (11.3% vs 1.3%), which is consistent with the drug’s existing label from the phase 3 STELLAR trial (NCT04576988). The label continues to direct health care professionals to monitor hemoglobin and platelets before each of the first 5 doses and periodically thereafter and to withhold treatment initiation if platelet count is below 50,000/mm³, given the drug’s association with thrombocytopenia and bleeding risk.¹

Where This Fits With Updated Treatment Guidelines

The approval lands weeks after the European Respiratory Society (ERS) published a focused guideline update that, for the first time, formally recommends sotatercept as an add-on therapy for patients with PAH at intermediate-low, intermediate-high, or high risk who are already on background treatment—a “strong” recommendation backed by “high” certainty of evidence, the only add-on PAH therapy to receive that grade in the update. Read alongside HYPERION, the guideline update, and the new label data point in the same direction: Earlier consideration of sotatercept for patients who haven't reached low-risk status on existing therapy.^1,4

Pharmacist Considerations

For pharmacists, the earlier-diagnosis indication does not change the counseling fundamentals so much as it moves them earlier in a patient's care. Baseline and predose hemoglobin and platelet monitoring should be built into the first 5 doses regardless of how recently a patient was diagnosed, and patients should be counseled on subcutaneous injection technique, storage, and the every-3-week schedule from the start.⁴

Medication reconciliation should specifically surface concomitant oral anticoagulant use, since bleeding risk—epistaxis most commonly—is the AE most likely to prompt a call to the pharmacy, and patients should be told to report nosebleeds, unusual bruising, or bleeding that doesn’t stop rather than adjust or stop dosing on their own.^1,4

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. Released 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. 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 September 22, 2026. https://clinicaltrials.gov/study/NCT04811092

3. 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

4. Halpern L. ERS adds sotatercept to pulmonary arterial hypertension treatment guidelines. Pharmacy Times. September 16, 2026 (updated September 17, 2026). Accessed September 22, 2026. https://www.pharmacytimes.com/view/ers-adds-sotatercept-to-pah-treatment-guidelines