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Data from the phase 3 STELLAR trial indicate adding sotatercept to background therapy in PAH was associated with statistically significant improvements in 6-minute walk distance and 8 of the trial's 9 secondary endpoints, including time to death or clinical worsening.
New research from the STELLAR trial suggests adding sotatercept to optimal background therapy was associated with a statistically significant improvement in 6-minute walk distance and other relevant endpoints in adults with pulmonary arterial hypertension (PAH).
Presented at the American College of Cardiology’s (ACC) 2023 Annual Scientific Session Together With the World Congress of Cardiology, results of the phase 3 trial suggests sotatercept was associated with improvements in the primary endpoint and 8 of the trial’s 9 secondary endpoints, including the percentage of patients meeting a multicomponent measure requiring an increase of at least 30 meters in the 6-minute walk distance together with achievement or maintenance of a favorable World Health Organization (WHO) functional class and NT-proBNP level.1
“These results establish the clinical utility of sotatercept as a new approach to the treatment of PAH in combination with existing approved therapies,” said lead investigator Marius M. Hoeper, MD, of Hannover Medical School.2 “It’s really a paradigm shift in how we will treat PAH in the future.”
A multicenter, double-blind, phase 3 trial of adults with WHO functional class II or III PAH who were receiving stable background therapy, STEALLAR randomized patients in a 1:1 ratio to receive subcutaneous sotatercept or placebo therapy every 3 weeks. Funded by Acceleron Pharma, which is a subsidiary of Merck and Company, the trial started patients randomized to sotatercept to a starting dose of 0.3 mg per kilogram of body weight, with a target dose of 0.7 mg per kilogram of body weight.1
The trial’s primary endpoint was the change from baseline to week 24 in 6-minute walk distance. The trial also included 9 secondary endpoints, which were tested hierarchically in the following order1:
Investigators pointed out all endpoints in the study were assessed at week 24 except time to death or clinical worsening, which was assessed when the final patient completed the week 24 visit.1
Overall, 323 patients were enrolled from centers in 20 countries, with 163 randomized to sotatercept and 160 randomized to placebo therapy. The overall study cohort had a mean age of 47.9 (SD, 14.8) year, 79.3% were female, 89.2% were non-Hispanic White, and 84.5% were recruited from centers in Europe or North America. Investigators pointed out 48.6% of patients had WHO functional class II PAH and 51.4% met criteria for WHO functional class III.1
Upon analysis, results indicated the median change from baseline to week 24 in 6-minute walk distance was 34.4 meters (95% CI, 33.0 to 35.5) among those in the sotatercept group and 1.0 meters (95% CI, -0.3 to 3.5) in the placebo group, with additional analysis indicatinggroups in the change from baseline at week 24 in the 6-minute walk distance was 40.8 meters (95% CI, 27.5 to 54.1; P <.001) in favor of sotatercept. Analysis of secondary endpoints revealed significant improvement in 8 of the 9 secondary endpoints with use of sotatercept, with PAH-SYMPACT Cognitive-Emotional Impacts domain score as the lone exception.1
Analysis of safety data from the trial suggested epistaxis, dizziness, telangiectasia, increased hemoglobin levels, thrombocytopenia, and increased blood pressure occurred more frequently among the sotatercept arm than among the placebo arm.1
In an editorial comment, Darren B. Taichman, MD, PhD, Jane Leopold, MD, and Greg Elliott, MD, celebrated the results of the STELLAR trial but noted large gaps in management still remain for this difficult to treat population.
“The STELLAR trial provides encouraging data for a new direction in therapeutic strategies for pulmonary arterial hypertension, 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,” the trio concluded.3