FDA records a Winrevair efficacy approval as a high-risk PAH trial cut deaths

The Food and Drug Administration has logged a new efficacy approval for Winrevair, Merck's injectable pulmonary arterial hypertension (PAH) drug sotatercept. The action was recorded in the agency's Drugs@FDA database on 21 September 2026 under biologics licence application 761363, held by Merck Sharp & Dohme, as an efficacy supplement to the existing approval; the product is an injectable supplied at 60 mg [s2]. Winrevair is already labelled for adults with pulmonary arterial hypertension, Group 1 pulmonary hypertension, to improve exercise capacity and World Health Organization (WHO) functional class [s3].

Sotatercept is an activin-signalling inhibitor, a different mechanism from the vasodilator drugs that have dominated PAH care. Its first approval rested on patients with milder disease. The newest data, and the reason the regulatory file matters, come from a trial run in the sickest patients — those an earlier generation of PAH drugs has least to offer.

What the ZENITH trial tested

ZENITH was a phase 3, placebo-controlled trial in adults with PAH in WHO functional class III or IV and a high one-year risk of death, defined by a REVEAL Lite 2 risk score of at least 9, all of whom were already on the maximum tolerated dose of background therapy [s1]. It randomly assigned 172 patients — 86 to add-on sotatercept and 86 to placebo — with sotatercept started at 0.3 mg per kilogram and escalated to a target of 0.7 mg per kilogram every three weeks [s1].

The primary endpoint was a composite of death from any cause, lung transplantation, or hospitalisation of at least 24 hours for worsening PAH, measured as the time to a first event [s1]. That is a harder, more consequential endpoint than the exercise-distance measures PAH trials have often relied on.

What it found

At least one primary-endpoint event occurred in 15 patients (17.4%) on sotatercept and in 47 patients (54.7%) on placebo — a hazard ratio of 0.24 (95% confidence interval 0.13 to 0.43; P<0.001) [s1]. The trial was stopped early on the basis of a prespecified interim analysis [s1].

The components moved in the same direction. Death from any cause occurred in 7 patients (8.1%) on sotatercept versus 13 (15.1%) on placebo; lung transplantation in 1 (1.2%) versus 6 (7.0%); and hospitalisation for worsening PAH in 8 (9.3%) versus 43 (50.0%) [s1]. The most common adverse events with sotatercept were epistaxis and telangiectasia [s1].

How to read it

These were not newly diagnosed patients. Every participant was already receiving the maximum tolerated dose of background PAH therapy when sotatercept or placebo was added, so the trial tested what the drug adds on top of existing treatment rather than what it does in its place [s1]. That framing matters: the benefit recorded is incremental, layered onto the vasodilator-based regimens these patients were already taking, and it was achieved in people whose one-year risk of death was high enough to qualify them for the study [s1]. It also means the comparison is against optimised standard care, not against no treatment — the harder test of the two.

A hazard ratio of 0.24 is a large effect, and it was seen in patients defined by their high near-term risk of death — a group in which any treatment benefit is both harder to achieve and more meaningful [s1]. Two cautions temper the reading. Trials halted early for benefit can overstate the size of an effect, because they stop at a favourable moment. And the composite is driven heavily by hospitalisation, the softest of its three parts: hospitalisation fell from 50.0% to 9.3%, while the mortality difference, though in the drug's favour, rested on smaller numbers [s1].

The bleeding-related adverse events — nosebleeds and small vessel malformations — are consistent with the drug's biology and are the practical signal to watch as it reaches sicker, frailer patients than those in the first trials [s1].

What to watch

The near-term questions are how the labelling defines the high-risk population the supplement reflects, and whether the survival signal holds beyond a trial that stopped early [s1]. Longer follow-up and real-world use in advanced PAH will decide whether the ZENITH result is reproduced outside a controlled study.

Red flags: anyone taking sotatercept who has heavy or recurrent nosebleeds, unusual bruising or bleeding, or sudden worsening breathlessness should seek medical care promptly [s1]. This article describes research and regulatory news and is not medical advice. Decisions about PAH treatment are for patients and their treating clinicians.

Sources

• Sotatercept in Patients with Pulmonary Arterial Hypertension at High Risk of Death (ZENITH) — New England Journal of Medicine, 31 March 2025
• Drugs@FDA: Winrevair (sotatercept-csrk), BLA 761363 — efficacy supplement approval record — U.S. Food and Drug Administration, approved 21 September 2026
• Label: Winrevair (sotatercept-csrk) — indications and usage — U.S. Food and Drug Administration, effective 12 August 2026