SHERIDAN, WYOMING - December 19, 2025 - Merck said the EMA's CHMP has recommended approval of an expanded European indication for WINREVAIR (sotatercept) in adults with pulmonary arterial hypertension (PAH), a move that-if confirmed by the European Commission-could broaden use to include WHO Functional Class (FC) IV patients and strengthen the product's positioning around morbidity and mortality benefit.
Regulatory pathway and timing across Europe's key markets
Merck announced the CHMP recommended the approval of an expanded indication for WINREVAIR, in combination with other PAH therapies, for adults with WHO FC II, III, and IV based on the Phase 3 ZENITH study. The company said the current EU indication covers adults with PAH WHO FC II to III to improve exercise capacity. The CHMP recommendation will now be reviewed by the European Commission for amending the marketing authorization in the EU, Iceland, Liechtenstein and Norway, with a final decision expected in Q1 2026.
For commercial planning, the EC decision is the key gating event: label scope in FC IV can influence specialist prescribing patterns, guideline evolution, and the sequencing of combination regimens in high-risk PAH.
From exercise capacity to harder outcomes: what the label expansion implies
Merck is framing the expansion as more than incremental. If approved, the broader indication would extend use beyond improvement in exercise capacity toward outcomes tied to major morbidity and mortality-an important differentiation lever in a category where payers and prescribers increasingly look for evidence that translates into fewer hospitalizations, delayed progression, and survival benefit.
"If approved, this broader indication would recognize the impact of WINREVAIR on morbidity and mortality in adult patients with PAH, extending the overall use of WINREVAIR to be inclusive of WHO FC II, III and now IV patients, with a treatment objective beyond the improvement of exercise capacity," said Dr. Joerg Koglin, senior vice president and head of general medicine, global clinical development, Merck Research Laboratories. "We look forward to the EC's decision as we work to ensure broad patient access to the first and only activin signaling inhibitor therapy approved in Europe and continue to deliver meaningful evidence to support treatment decisions."
ZENITH data: magnitude of effect and early stop signal
Merck said the CHMP recommendation is based on Phase 3 ZENITH, where adding WINREVAIR to background therapy resulted in a 76% reduction in the risk of major morbidity and mortality outcomes versus placebo (HR: 0.24; 95% CI: 0.13-0.43; p<0.0001) in adults with PAH WHO FC III or IV. The composite primary endpoint-time to first occurrence of all-cause death, lung transplantation, or PAH-worsening hospitalization of ≥24 hours-occurred in 15 WINREVAIR-treated participants (17%) versus 47 placebo-treated participants (55%). Merck noted the trial was stopped early at interim analysis due to overwhelming efficacy, and patients were offered entry into an open-label long-term follow-up study, with results published in the New England Journal of Medicine.
Operationally, an early-stop outcome can intensify demand for rapid evidence translation (real-world follow-up, subgroup analyses, implementation in care pathways) as physicians evaluate where the therapy fits for advanced patients already on complex regimens.
How this fits Merck's global footprint and PAH market dynamics
Merck said WINREVAIR is approved in all 27 EU member states as well as Iceland, Liechtenstein and Norway, and is approved in more than 50 countries. The company added that in October 2025, the U.S. FDA approved an updated indication based on ZENITH, with U.S. labeling now including reduced risk of clinical worsening events such as hospitalization, lung transplantation and death.
From a competitive standpoint, expanding EU label breadth to FC IV could widen the addressable segment and reinforce WINREVAIR's role alongside established PAH backbones-especially in high-risk populations where decision-makers prioritize outcome-driven differentiation.
Trial design context that matters to clinicians and health systems
Merck described ZENITH as a global, double-blind, placebo-controlled trial enrolling 172 adult participants with PAH WHO FC III or IV at high mortality risk, randomized 1:1 to WINREVAIR (target dose 0.7 mg/kg) plus background therapy versus placebo plus background therapy, administered subcutaneously once every three weeks. Most participants were on advanced background treatment (including substantial use of triple therapy and prostacyclin infusion), making the data particularly relevant to real-world specialist settings managing severe disease.
For healthcare professional product information on WINREVAIR, visit https://www.merckconnect.com/winrevair/.