RAHWAY, N.J., Sept. 30, 2025 – Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced compelling Phase 3 results from the HYPERION trial of WINREVAIR™ (sotatercept-csrk), demonstrating a 76% reduction in clinical worsening events compared to placebo in patients recently diagnosed with pulmonary arterial hypertension (PAH). The findings, unveiled at the European Respiratory Society (ERS) Congress 2025 and published simultaneously in the New England Journal of Medicine, underscore the therapy’s potential to reshape early treatment strategies for this life-threatening condition.

Science Significance

PAH is a rare, progressive vascular disorder that significantly shortens life expectancy, with a five-year mortality rate of around 43%. Existing therapies have helped delay disease progression but remain limited in changing the long-term course, especially when initiated early.

WINREVAIR is the first activin signaling inhibitor approved for PAH. By restoring the balance between pro-proliferative and anti-proliferative pathways, the therapy addresses a fundamental driver of vascular remodeling in the disease.

The HYPERION trial stands out for enrolling patients within the first year of PAH diagnosis (median seven months, as early as one month), offering unique insight into the benefits of initiating novel targeted therapy early in the treatment journey. Within just six weeks of randomization, Kaplan-Meier curves revealed early and sustained separation favoring WINREVAIR, a clear signal of robust efficacy in halting disease worsening.

Regulatory Significance

Results from HYPERION will be submitted to regulatory agencies worldwide, extending beyond the 54 countries where WINREVAIR is already approved based on earlier pivotal studies such as STELLAR and ZENITH.

Regulators are expected to closely evaluate the statistically significant improvements in both primary and secondary endpoints, including reductions in all-cause death, unplanned PAH hospitalizations, lung transplantation, and deterioration in functional class.

By expanding evidence to newly diagnosed patients, HYPERION may support label expansion to earlier stages of disease, potentially altering standard-of-care protocols and broadening patient eligibility for sotatercept-based therapy.

Business Significance

PAH represents a high-value orphan market with significant unmet need. With only about 90,000 patients worldwide, it is a rare disease but one with substantial therapeutic cost and limited competition in first-in-class mechanisms.Merck, through its licensing agreement with Bristol Myers Squibb, positions WINREVAIR as a cornerstone growth driver in specialty medicine. The drug’s strong efficacy profile in multiple Phase 3 trials (STELLAR, ZENITH, and now HYPERION) reinforces its commercial trajectory and potential expansion into broader patient pools.With PAH treatments already commanding premium reimbursement due to disease severity and lack of alternatives, these results bolster Merck’s case for payer adoption and long-term revenue impact.

Patients’ Significance

For patients, the HYPERION trial offers tangible hope in the earliest phases of a devastating disease. In the study, only 10.6% of patients on WINREVAIR experienced a clinical worsening event compared to 36.9% in the placebo group – a remarkable difference that directly translates to improved quality of life and survival prospects.

Moreover, 29.4% of WINREVAIR patients achieved multicomponent improvement (across functional class, biomarkers, and exercise capacity), compared to only 14.6% on placebo. Such multidimensional benefits are rare in PAH studies, highlighting the therapy’s broad patient impact. Importantly, the safety profile remained consistent with prior studies, with adverse events largely manageable and comparable to placebo, making the therapy viable for long-term administration.

Policy Significance

From a policy perspective, early intervention in PAH has long been a priority, given the condition’s rapid progression and healthcare burden from repeated hospitalizations and high-cost interventions such as lung transplantation.

WINREVAIR’s strong Phase 3 evidence could drive updates to international PAH treatment guidelines, supporting its use within the first year of diagnosis. Such changes may prompt healthcare systems to reallocate resources toward early adoption, potentially reducing downstream costs associated with advanced disease management.

Additionally, the trial’s global footprint provides regulators, payers, and policymakers with robust real-world applicability, reinforcing the case for broad access and reimbursement.

Transaction Highlights

The Phase 3 HYPERION trial demonstrated that WINREVAIR™ (sotatercept-csrk) reduced the risk of clinical worsening events by 76% compared with placebo, when added to background therapy in newly diagnosed pulmonary arterial hypertension (PAH) patients. The study enrolled 320 participants within the first year of diagnosis, with over 70% receiving double background therapy, reflecting real-world treatment settings. Results showed an early and sustained separation in outcomes as early as six weeks, with only 10.6% of WINREVAIR patients experiencing a clinical worsening event versus 36.9% in the placebo group. Importantly, WINREVAIR also achieved significant improvements in key secondary endpoints, including multicomponent clinical improvement and maintenance or achievement of low REVEAL Lite 2 risk scores, reinforcing its broad clinical benefit. Safety results were consistent with prior trials, with manageable adverse events and no new safety signals identified. As the third positive Phase 3 trial of WINREVAIR, following STELLAR and ZENITH, HYPERION further supports Merck’s confidence in the therapy’s practice-changing potential. Results were presented at ERS 2025 and simultaneously published in the New England Journal of Medicine. Merck now plans to submit these data to global regulatory authorities to expand WINREVAIR’s indication into earlier stages of PAH treatment.

Source: Merck Sharp & Dohme Press Release