Merck's WINREVAIR™ (sotatercept) Approved in Europe for Adult PAH Treatment

Merck, also recognized as MSD outside of the United States and Canada, has announced that the European Commission (EC) has approved WINREVAIR™ (sotatercept). This approval allows the drug to be used in conjunction with other therapies for treating pulmonary arterial hypertension (PAH) in adult patients classified as World Health Organization (WHO) Functional Class (FC) II to III. WINREVAIR aims to enhance exercise capacity and is the first activin signaling inhibitor therapy for PAH sanctioned in all 27 EU member states, Iceland, Liechtenstein, and Norway.

WINREVAIR operates by adjusting the equilibrium between pro- and anti-proliferative signaling, which manages the vascular cell proliferation associated with PAH. The EC's approval is based on the results of the Phase 3 STELLAR trial, which highlighted the safety and efficacy of the drug.

Dr. Joerg Koglin, a senior vice president at Merck Research Laboratories, emphasized the importance of this approval, stating that WINREVAIR is the first therapy to target the activin signaling pathway. This innovative treatment is expected to benefit more patients, and Merck remains committed to exploring further potential applications of WINREVAIR in managing PAH.

Dr. Marc Humbert, Professor of Medicine at Université Paris-Saclay, noted the severe impact of PAH on patients, who often experience debilitating symptoms that limit daily activities. According to Dr. Humbert, the Phase 3 STELLAR study demonstrated that adding WINREVAIR to existing PAH therapies significantly improved exercise capacity, reduced the risk of death or clinical worsening events, and enhanced functional class compared to using background PAH therapy alone. These findings suggest that WINREVAIR, used in combination with other PAH treatments, could become a new standard of care for adult patients in functional classes II and III.

The Phase 3 STELLAR trial involved 323 adult PAH patients (WHO Group 1, FC II or III), who were randomly assigned to receive either WINREVAIR (163 patients) or a placebo (160 patients) alongside their standard care. The primary efficacy measure was the change in six-minute walk distance from baseline to Week 24. Treatment with WINREVAIR led to a significant and clinically meaningful improvement in this distance by 40.8 meters over the placebo. The drug also notably enhanced several secondary outcomes, including reducing the risk of death or clinical worsening. An additional analysis showed that WINREVAIR reduced the risk of death or clinical worsening by 82% compared to background therapy alone.

WINREVAIR is administered as a subcutaneous injection every three weeks. Patients or caregivers can administer it with proper training, guidance, and follow-up from healthcare providers. Detailed instructions for the preparation and administration of WINREVAIR are available for healthcare providers and patients.

The EC approval extends to all 27 EU member states as well as Iceland, Liechtenstein, and Norway. Previously, WINREVAIR received Priority Medicines (PRIME) and orphan designation by the EMA for treating PAH. In March 2024, the FDA approved WINREVAIR in the United States for treating adults with PAH to improve exercise capacity, enhance WHO functional class, and reduce the incidence of clinical worsening events.

The STELLAR trial, a double-blind, placebo-controlled clinical study, included participants with various PAH etiologies such as idiopathic PAH, heritable PAH, and PAH associated with connective tissue diseases. The majority of participants were already receiving two or three background drugs for PAH, with a significant portion also on prostacyclin infusions.

WINREVAIR, the first approved activin signaling inhibitor therapy for PAH, aims to balance pro-proliferative and anti-proliferative signaling to regulate vascular proliferation. Preclinical models showed that WINREVAIR could induce cellular changes leading to thinner vessel walls, partial reversal of right ventricular remodeling, and improved hemodynamics.

In summary, the EC's approval of WINREVAIR marks a significant advancement in PAH treatment, offering new hope and improved management for patients suffering from this debilitating condition.