Patients with pulmonary arterial hypertension (PAH) who were treated with sotatercept on top of existing therapy experienced significant improvements in exercise capacity, according to findings from the STELLAR trial, presented at ACC.23/WCC and simultaneously published in the New England Journal of Medicine.

Marius M. Hoeper, MD, et al., conducted a multicenter, double-blind, phase 3 trial randomizing 163 patients with WHO functional class II or III PAH to receive subcutaneous sotatercept (starting dose, 0.3 mg/kg of body weight; target dose, 0.7 mg/kg) and 160 patients to receive a placebo every three weeks. Researchers defined the primary endpoint as the change from baseline at week 24 in the 6-minute walk distance (6MWD).

Results showed a median change from baseline at week 24 in the 6MWD of 34.4 meters (95% CI, 33.0-35.5) in the sotatercept arm vs. 1.0 m (95% CI, –0.3 to 3.5) in the placebo arm. Researchers found the Hodges-Lehmann estimate of the difference in change between the two arms was 40.8 m (95% CI, 27.5-54.1; p<0.001).

Various secondary endpoints, including multicomponent improvement, change in pulmonary vascular resistance, change in N-terminal pro–B-type natriuretic peptide level, and improvement in WHO functional class, among others, additionally showed significant improvement with sotatercept vs. placebo, but improvement was not seen for the Pulmonary Arterial Hypertension–Symptoms and Impact Cognitive–Emotional Impacts domain score. Incidences of adverse events including epistaxis, dizziness, telangiectasia, increased hemoglobin levels, thrombocytopenia and increased blood pressure were more common in the sotatercept group.

"These results establish the clinical utility of sotatercept as a new approach to the treatment of PAH in combination with existing approved therapies," said Hoeper. "It's really a paradigm shift in how we will treat PAH in the future."

In an accompanying editorial comment, Darren B. Taichman, MD, PhD; Jane A. Leopold, MD, FACC; and Greg Elliott, MD, write: "The STELLAR trial provides encouraging data for a new direction in therapeutic strategies for [PAH], and it forces us to ask whether a new treatment era for the disorder has arrived. It's too soon to know. But one thing is clear: the era of remarkable progress in the care of patients with this devastating disease has not come to an end."

Clinical Topics: Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Prevention, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Pulmonary Hypertension, Hypertension

Keywords: ACC Annual Scientific Session, ACC23, Pulmonary Arterial Hypertension, Familial Primary Pulmonary Hypertension, Hypertension, Pulmonary

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