Merck announced that the U.S. Food and Drug Administration (FDA) approved the activin signaling inhibitor sotatercept-csrk (Winrevair) for the treatment of adult patients with pulmonary arterial hypertension. Sotatercept works by balancing pro- and antiproliferative signaling to regulate vascular cell proliferation. The approval comes after positive results were reported in the phase III STELLAR trial (ClinicalTrials.gov identifier NCT04576988). In the trial, patients with World Health Organization (WHO) Group 1 functional class II or III pulmonary arterial hypertension were randomly assigned to receive either a subcutaneous injection of sotatercept (n = 163) once every 3 weeks or placebo (n = 160) in combination with background therapy. Compared with placebo, sotatercept improved exercise capacity by increasing the 6-minute walking distance by 41 m from baseline to 24 weeks (95% confidence interval [CI] = 28–54), improved WHO functional class in 29% vs 14% of patients, and reduced the risk of all-cause and clinical worsening events–related mortality by 84% (number of events = 9 vs 42, hazard ratio = 0.16, 95% CI = 0.08–0.35). However, patients in the sotatercept group were found to have higher hemoglobin levels, which heightened the risks of erythrocytosis, thromboembolic events, and hyperviscosity syndrome, as well as lower platelet counts, which increased the likelihood of thrombocytopenia and bleeding. To determine whether dose adjustments may be necessary, physicians were advised to monitor patients’ hemoglobin and platelet levels prior to each dose of sotatercept for at least five doses or until values are stable, as well as periodically thereafter. “Based on the phase [III] STELLAR trial, adding [sotatercept] to [pulmonary arterial hypertension] background therapy demonstrated significant clinical benefits compared [with] background … therapy alone. This approval is an important milestone, as it offers health-care providers a novel therapeutic option that targets a new [pulmonary arterial hypertension] pathway,” concluded senior study author Marc Humbert, MD, PhD, Professor of Medicine and Director of the Pulmonary Hypertension Reference Center at the Université Paris-Saclay.