Merck's WINREVAIR™ Demonstrates Significant Efficacy in Recently Diagnosed PAH Patients

WINREVAIR™ Demonstrates Significant Efficacy in Early-Stage PAH Patients

Merck (MRK) announced compelling positive results from its Phase 3 HYPERION trial for WINREVAIR™ (sotatercept-csrk), its first-in-class activin signaling inhibitor therapy for Pulmonary Arterial Hypertension (PAH). The data, unveiled at the 2025 European Respiratory Society (ERS) Congress and simultaneously published in the New England Journal of Medicine, indicate a substantial reduction in clinical worsening events for recently diagnosed adult PAH patients.

Detailed Trial Outcomes

The HYPERION study, involving 320 adults diagnosed with PAH within the last year and on stable background therapy, met its primary endpoint by demonstrating a 76% reduction in the risk of clinical worsening events compared to placebo. Specifically, only 10.6% of WINREVAIR™-treated patients experienced a clinical worsening event, versus 36.9% in the placebo group. The trial also highlighted an early and sustained separation in Kaplan-Meier curves, with treatment benefits observed within six weeks of randomization and consistency across all prespecified subgroups.

Beyond the primary endpoint, WINREVAIR™ showed statistically significant improvements in key secondary endpoints. 29.4% of treated patients achieved multicomponent improvement (defined by improvements in six-minute walk distance, NT-proBNP levels, and WHO functional class), compared to 14.6% on placebo. Furthermore, 60.1% of WINREVAIR™-treated patients maintained or achieved a low REVEAL Lite 2 risk score relative to baseline at week 24, versus 47.9% in the placebo group. The safety profile of WINREVAIR™ in the HYPERION trial was generally consistent with previous observations from earlier trials, including the pivotal STELLAR study that supported its initial U.S. approval.

Market Reaction and Broader Implications

The announcement has generated a bullish sentiment around Merck's stock (MRK), as these results significantly expand the clinical evidence base for WINREVAIR™. This data supports the drug's potential use earlier in the disease course, potentially broadening its addressable patient population and increasing market penetration. The drug is already approved in over 54 countries based on the STELLAR study, which focused on patients with an average PAH duration of 8.8 years. The HYPERION trial's focus on newly diagnosed patients presents a distinct growth opportunity.

Merck is strategically positioning WINREVAIR™ as a key growth driver, particularly as its blockbuster oncology drug Keytruda approaches patent expiry. The company has increased its peak sales guidance for its cardiometabolic franchise, which includes WINREVAIR™, from over $10 billion to approximately $15 billion, reflecting strong internal confidence. Analysts estimate WINREVAIR™'s peak annual sales potential to be at least $2 billion, with some projections reaching $3 billion to $4 billion. The PAH market, valued at $7.3 billion in 2023, is projected to grow to $12.2 billion by 2032, offering a substantial and expanding opportunity.

Merck's financial health remains robust, underpinned by a market capitalization of approximately $198.5 billion to $225 billion, gross profit margins of 77%, and a distinguished record of 55 consecutive years of dividend payments. InvestingPro analysts currently identify Merck as undervalued, trading near its 52-week low, with an EPS forecast of $8.93 for fiscal year 2025. Morgan Stanley maintains an Equalweight rating with a $99.00 price target.

Expert Perspectives

Industry experts underscore the significance of these findings:

"The totality of Winrevair data to date continues to reinforce our confidence in its practice-changing potential," stated Joerg Koglin, head of general and specialty medicine at Merck Research Laboratories.

"The patients with PAH enrolled in HYPERION were early in their treatment journey, had co-morbidities and were older, which reflects the type of patients we are diagnosing in a contemporary real-world setting," noted Dr. Vallerie McLaughlin, Director of the Pulmonary Hypertension Program at the University of Michigan.

These comments highlight the drug's potential to redefine early-stage PAH management and address the needs of a diverse patient population.

Outlook

Merck plans to submit the HYPERION results to regulatory authorities globally, with the aim of expanding WINREVAIR™'s label to include recently diagnosed PAH patients. This move, alongside ongoing efforts to incorporate data from the Phase III ZENITH trial for the most severe PAH patients (with an FDA decision slated by October 25), positions Merck to capture a broader spectrum of the PAH market. The novel mechanism of WINREVAIR™, which inhibits activin signaling, offers a distinct advantage in a market previously dominated by therapies targeting vasodilation or endothelial pathways. The drug's "first-in-class" status and compelling efficacy data suggest it could carve out a significant niche, enhancing Merck's long-term growth trajectory and leadership in rare disease innovation.