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Merk announced today that its first-in-class drug, sotatercept-csrk (Winrevair), for the treatment of pulmonary arterial hypertension (PAH) has been approved by the U.S Food and Drug Administration (FDA). The drug has shown that it increases exercise capacity and reduces the risk of clinically worsening events.

Sotatercept is the first FDA-approved activin signaling inhibitor that works by improving the balance between pro- and anti-proliferative signaling to regulate the vascular proliferation underlying PAH. The drug previously was granted a Breakthrough Therapy designation by the FDA, and represents a new class of therapy for this condition.

The approval is based on the Phase III STELLAR trial, a double-blind, clinical trial in which adults with pulmonary arterial hypertension (World Health Organization [WHO] functional class II or III) who were receiving stable background therapy were randomly assigned in a 1:1 ratio to receive subcutaneous sotatercept (starting dose, 0.3 mg per kilogram of body weight; target dose, 0.7 mg per kilogram) or placebo every three weeks. The primary endpoint was the change from baseline at week 24 in the six-minute walk distance.

Results showed adding sotatercept to background therapy increased six-minute walk distance from baseline by 41 meters after 24 weeks and significantly improved multiple important secondary outcome measures, including reducing the risk of death from any cause or PAH clinical worsening events by 84% versus background therapy alone.

“Pulmonary arterial hypertension is a rare, progressive and ultimately life-threatening disease in which blood vessels in the lungs thicken and narrow, causing significant strain on the heart,” said Marc Humbert, professor of medicine and director of the Pulmonary Hypertension Reference Center at the Université Paris-Saclay and investigator on the study. “This approval is an important milestone, as it offers healthcare providers a novel therapeutic option that targets a new PAH treatment pathway.”

Merck notes that healthcare providers should monitor hemoglobin and platelet levels of patients before doses of sotatercept for the first five doses, or longer if a patient’s values are unstable. Monitoring should also occur periodically to determine if a dose adjustment is necessary. Potential side effects of the drug include an increase in hemoglobin which may lead to erythrocytosis, which if severe may increase the risk of thromboembolic events or hyperviscosity syndrome. It may also decrease a patient’s platelet count leading to severe thrombocytopenia, which may increase the risk of bleeding.

Sotatercept is delivered once every three weeks to patients via a subcutaneous injection.

“New treatment options continue to be needed for patients with pulmonary arterial hypertension that support important clinical goals, including increasing exercise capacity and improving functional class,” said study investigator Aaron Waxman, MD, PhD, executive director of the Center for Pulmonary Heart Diseases at Brigham and Women’s Hospital. “Sotatercept added to background therapy has the potential to become a new standard of care option for patients with pulmonary arterial hypertension.”

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