Sotatercept was associated with greater improvement in exercise capacity compared with placebo among patients with pulmonary arterial hypertension who were receiving stable background therapy, according to study findings published in the New England Journal of Medicine.
Researchers evaluated the efficacy and safety of sotatercept in adult patients with symptomatic pulmonary arterial hypertension in the phase 3, multicenter, double-blind, randomized, placebo-controlled STELLAR trial (ClinicalTrials.gov Identifier: NCT04576988). The study’s primary endpoint was the change from baseline to week 24 in 6-minute walk distance. Researchers also evaluated a number of secondary endpoints, including change in pulmonary vascular resistance, change in N-terminal
pro-B-type natriuretic peptide level, improvement in WHO functional class, and time to death or clinical worsening.
Eligible patients were stratified based on World Health Organization (WHO) functional class (II vs III) and background therapy for pulmonary arterial hypertension (monotherapy or double therapy vs triple therapy) and were randomly assigned 1:1 to receive sotatercept or placebo combined with stable background therapy. Sotatercept was initiated at a dose of 0.3 mg per kilogram at visit 1 and then escalated to the target dose of 0.7 mg per kilogram at visit 2 (day 21, ±3 days).
A total of 163 patients received sotatercept and 160 received placebo, with all receiving stable background therapy. The participants had a mean (SD) age of 47.9 [14.8] years and a mean length of time since diagnosis of 8.8 years.
The sotatercept group had a mean change at week 24 in 6-minute walk distance of 40.1 meters (95% CI, 29.9-50.2) compared with -1.4 meters (95% CI, −13.2 to 10.3) in the placebo group. The median change from baseline in 6-minute walk distance was 34.4 meters (95% CI, 33.0-35.5) for participants who received sotatercept and 1.0 m (95% CI, -0.3 to 3.5) for those who received placebo. The post hoc analysis of 6-minute walk distance showed comparable findings with those of the prespecified analysis.
With respect to secondary study outcomes, improvement in a multicomponent measure that included 6-minute walk distance, N-terminal pro–B-type natriuretic peptide level, and WHO functional class was seen in 39% of those in the sotatercept group vs 10% of those in the placebo group. Significant improvements from baseline to week 24 were observed with sotatercept vs placebo in pulmonary vascular resistance, NT-proBNP levels, and WHO functional class. A significant difference was also observed in the distribution of time to first occurrence of death or nonfatal clinical worsening event between the sotatercept vs placebo groups.
Serious adverse events were reported in 23 patients (14.1%) in the sotatercept group compared with 36 patients (22.5%) in the placebo group; notably, investigators indicated that there were likely only 2 patients (1.2%) in each group whose adverse events were related to either sotatercept or placebo. The most common adverse events were bleeding events (35 patients [21.5%] in the sotatercept group vs 20 [12.5%] in the placebo group).
Study limitations include the enrollment of only WHO functional class II or III patients with certain forms of pulmonary arterial hypertension. In addition, there is potential unblinding owing to side effects such as telangiectasia or hematologic changes. Furthermore, the median treatment of 7.5 months precluded the ability to establish the long-term durability of the treatment response.
“In this trial, treatment with sotatercept improved exercise capacity as determined by the 6-minute walk distance and showed clinical benefit across multiple efficacy end points,” concluded study authors. “Sotatercept had a favorable benefit-risk ratio, findings that confirm and extend the results of previous studies,” they added.
Disclosure: This research was supported by Acceleron Pharma, a subsidiary of MSD. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Hoeper MM, Badesch DB, Ghofrani HA, et al. Phase 3 trial of sotatercept for treatment of pulmonary arterial hypertension. N Engl J Med. 2023;388(16):1478-1490. doi:10.1056/NEJMoa2213558