At its June 2024 meeting, the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) gave Winrevair (sotatercept; Merck Sharp & Dohme) a positive opinion for the treatment of patients with pulmonary arterial hypertension (PAH).
Despite approved therapies for treating PAH, long-term prognosis remains poor. It is estimated that around 50% of patients will die within 5-7 years after diagnosis.
Winrevair, in combination with other PAH therapies, is indicated for the treatment of PAH in adult patients with World Health Organization functional class II-III, to improve exercise capacity.
The benefit of Winrevair in patients with PAH on background therapy is an improvement in 6-minute walk distance compared with placebo.
The positive opinion means that the first-in-class medicine has been recommended for the granting of a marketing authorization in the European Union to treat adult patients with PAH, in combination with other specific PAH therapies, to improve exercise capacity.
Significantly Improved Exercise Capacity
Winrevair is a human recombinant fusion protein. It comprises the extracellular domain of the activin receptor type IIA attached to the Fc domain of human immunoglobulin G1. It acts as a ligand trap that scavenges excess activin A, which is increased in patients with PAH, to inhibit activin signaling, thereby modulating vascular cell proliferation, decreasing pulmonary vascular resistance, and improving hemodynamics.
The CHMP recommendation was based on the results of a randomized, double-blind, placebo-controlled, multicenter clinical trial that evaluated the efficacy and safety of sotatercept in 323 adults with PAH on stable treatment for more than 90 days with background PAH therapy (monotherapy or combination therapy).
Sotatercept was administered to 163 patients, whereas 160 were assigned to receive placebo.
In patients with PAH who were receiving stable background therapy, sotatercept resulted in a greater improvement in exercise capacity, as assessed by the 6-minute walk test, compared with placebo. The median change from baseline at week 24 in the 6-minute walk distance was 34.4 m in the sotatercept group and 1.0 m in the placebo group.
Adverse events that occurred more frequently with sotatercept than with placebo included epistaxis, dizziness, telangiectasia, increased hemoglobin levels (erythrocytosis), thrombocytopenia, and increased blood pressure.
Unmet Medical Need
The medicine is administered once every 3 weeks as a single subcutaneous injection. It may be administered by patients or caregivers with guidance, training, and follow-up from a healthcare provider.
Winrevair received support through the Priority Medicines (PRIME) scheme owing to its potential to bring a major therapeutic advantage over existing therapies. The scheme provides early and enhanced scientific and regulatory support for promising medicines with a potential to address unmet medical needs.
The opinion adopted by the CHMP is an intermediary step on the drug's path to patient access. The opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorization.