FDA Expands WINREVAIR Label With HYPERION Data

FDA has approved an update to the label for WINREVAIR (sotatercept-csrk), Merck's activin signaling inhibitor for pulmonary arterial hypertension, adding results from the Phase 3 HYPERION trial in adults diagnosed with PAH within the prior year. Merck announced the update on 22 September 2026. The headline number: a 76% relative reduction in the risk of clinical worsening events against placebo, on top of background therapy.

What the label picks up

WINREVAIR's indication does not narrow or expand with this update — it remains approved for adults with PAH generally. What changes is the evidence base behind it: the label now carries data specific to patients diagnosed with PAH within the previous 12 months, a population regulators and clinicians have increasingly flagged as one where earlier, more aggressive intervention could change the disease trajectory. Joerg Koglin, senior vice president and head of general and specialty medicine in global clinical development at Merck Research Laboratories, said in a statement that 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." He added that the trial evidence, together with updated treatment guidelines, is meant to inform care decisions about WINREVAIR's role for a broad range of PAH patients.

The HYPERION numbers

HYPERION enrolled 320 adults recently diagnosed with PAH, more than 70% of whom were already on double background therapy, and randomized them 1:1 to sotatercept or placebo. The trial's composite clinical-worsening endpoint bundled five outcomes: all-cause death, an unplanned PAH-related hospitalization lasting more than 24 hours, atrial septostomy, lung transplantation, or PAH deterioration. That composite event occurred in 10.6% of patients on sotatercept against 36.9% on placebo — a hazard ratio of 0.24 (95% CI 0.14–0.41, P<.0001). Merck's own announcement rounds those figures to roughly 11% and 37%, framed as a 76% relative risk reduction; both sets of numbers describe the same result, and the trial was published in the New England Journal of Medicine.

Where this sits in WINREVAIR's file

WINREVAIR reached the market on 26 March 2024 as the first FDA-approved activin signaling inhibitor and the first new PAH drug class in over a decade, built on the Phase 3 STELLAR trial in a broader PAH population already on background therapy. A later supplement, based on the separate Phase 3 ZENITH trial, extended the evidence file to higher-risk, hospitalized patients. HYPERION is a third and distinct trial, aimed specifically at the early-diagnosis window — the label update folds its results in without altering who is eligible to receive the drug. For RA/QA teams tracking the file, that distinction matters: this is a label expansion by evidence, not a new supplemental approval carving out a separate indication.

• Action: FDA approval of a supplemental labeling update to WINREVAIR (sotatercept-csrk), under Merck's existing biologics license.
• Announced: 22 September 2026, via Merck's own release.
• New data: Phase 3 HYPERION (NCT04811092), 320 patients, adults diagnosed with PAH within the prior 12 months.
• Result added to label: 76% relative risk reduction in a composite clinical-worsening endpoint versus placebo (10.6% vs. 36.9%, HR 0.24).
• Indication: unchanged — adults with PAH (WHO Group 1).
• Also new: a contraindication for serious hypersensitivity to sotatercept-csrk or its excipients.

Frequently asked questions

What did FDA approve on September 22, 2026?

An update to WINREVAIR's (sotatercept-csrk) U.S. label adding Phase 3 HYPERION trial data for adults with PAH diagnosed within the prior 12 months, on background therapy. It is a labeling supplement; WINREVAIR's approved indication for adults with PAH is unchanged.

What did the HYPERION trial show?

In 320 adults with recently diagnosed PAH randomized 1:1 to sotatercept or placebo plus background therapy, a composite clinical-worsening endpoint occurred in 10.6% on sotatercept versus 36.9% on placebo (HR 0.24, 95% CI 0.14–0.41, P<.0001) — a 76% relative risk reduction, published in the New England Journal of Medicine.

Does this change who WINREVAIR is approved for?

No. The label continues to cover adults with PAH (WHO Group 1) to increase exercise capacity, improve WHO functional class, and reduce clinical-worsening risk; HYPERION adds supporting evidence for the recently diagnosed subgroup without narrowing the existing indication.

What else changed in the label?

Merck said the update also adds a contraindication for serious hypersensitivity to sotatercept-csrk or its excipients. WINREVAIR was originally approved 26 March 2024 on the Phase 3 STELLAR trial; a separate earlier supplement added Phase 3 ZENITH data for higher-risk, hospitalized patients.