Results of the phase 2 PULSAR trial indicate sotatercept could be an effective adjunct to background medical therapy for reducing pulmonary vascular resistance in patients with pulmonary arterial hypertension.
A little less than a year after topline results were presented at ATS 2020, full data from the phase 2 PULSAR trial indicate sotatercept could be an effective treatment for patients with pulmonary arterial hypertension.
A novel, first-in-class fusion protein composed of the extracellular domain of the human activin receptor type IIA fused to the Fc domain of human IgG1, sotatercept was associated with reductions in pulmonary vascular resistance in patients already receiving background therapy for pulmonary arterial hypertension.
“The PULSAR data show that sotatercept has the potential to deliver significant benefit on top of currently available therapies,” said Marc Humbert, MD, PhD, investigator in the PULSAR trial and Professor of Medicine and Director of the French Pulmonary Hypertension Reference Center at the Université Paris-Saclay, in a statement from Acceleron Pharma. “This is a result that suggests that sotatercept could bring an important new mechanistic approach to the treatment of patients with PAH.”
A randomized, double-blind, placebo-controlled trial, PULSAR was designed to evaluate the safety and efficacy of sotatercept in patients with pulmonary arterial hypertension. A 24-week multicenter trial, the study enrolled 106 patients with WHO functional class II or IIII pulmonary arterial hypertension and randomized them in a 1:1:1 ratio to receive sotatercept at a dose of 0.3 mg per kilogram of body weight every 3 weeks or 0.7 mg per kilogram every 3 weeks or placebo therapy. The treatment portion of the trial was followed by an 18-month active-drug extension period that investigators noted is still ongoing.
Assessments of safety and efficacy were performed at screening and every 3 weeks after for 24 weeks. The primary end point of the trial was change from baseline to week 24 in pulmonary vascular resistance. Pulmonary vascular resistance was calculated using mean pulmonary artery pressure, the pulmonary artery wedge pressure, and cardiac output. Secondary end points for the trial included change from baseline to week 24 in 6-minute walk distance and changes in NT-proBNP, systolic excursion, and WHO functional class.
Upon conclusion of the trial, the least-squares mean difference between the sotatercept 0.3 mg group and the placebo group in the change from baseline to week 24 in pulmonary vascular resistance was −145.8 dyn·sec·cm5 (95% confidence interval [CI], −241.0 to −50.6; P=.003). When comparing the 0.7 mg group to the placebo group, the least-squares mean difference was −239.5 dyn·sec·cm5 (95% CI, −329.3 to −149.7; P <.001).
For the secondary end point, results indicated the least-squares mean difference between the sotatercept 0.3 mg group and the placebo group was 29.4 meters (95% CI, 3.8-55.0) When assessing the secondary end point in the 0.7 mg group, the least-squares mean difference in 6-minute walk distance was 21.4 meters (95% CI, -2.8 to 45.7). Additionally, the investigators’ analyses suggested sotatercept was associated with reduction in NT-proBNP.
When assessing safety, results indicated thrombocytopenia and increased hemoglobin levels were the most common hematological adverse events. Investigators also pointed out a single patient in the 0.7 mg group died from cardiac arrest during the trial.
According to the aforementioned statement, Acceleron Pharma noted the phase 3 STELLAR trial is currently ongoing and seeks to further examine use of sotatercept in patients with pulmonary arterial hypertension. Additionally, the company is also planning a pair of phase 3 trials to examine sotatercept in patients with WHO functional class IV pulmonary arterial hypertension.
This study, “Sotatercept for the Treatment of Pulmonary Arterial Hypertension,” was published in the New England Journal of Medicine.