A Long-Term Follow-Up Study of Sotatercept for Treatment of Pulmonary Arterial Hypertension: Interim Results of SOTERIA.

Background: SOTERIA (NCT04796337) is an ongoing open-label study evaluating long-term safety, tolerability, and efficacy of sotatercept in participants with pulmonary arterial hypertension (PAH).

Methods: Eligible adults with PAH on stable background therapy who completed a prior sotatercept study without early discontinuation were enrolled. Participants received subcutaneous sotatercept (≤0.7 mg·kg^-1 Q3W). Safety and tolerability (primary objective) were assessed by adverse events (AEs), vital signs, and laboratory assessments. Efficacy (secondary objective) was assessed by 6-minute walk distance (6MWD), N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, WHO functional class (FC), clinical worsening events, and simplified French risk score (SFRS). The data cutoff date was 08NOV2023.

Results: Altogether, 426 participants were included in the analyses. Mean (sd) duration of exposure to sotatercept and follow-up in SOTERIA was 448.6 (172.93) days (range 21-923 days; 523 patient-years). Of 426 participants, 387 (90.8%) experienced AEs, 15 (3.5%) discontinued treatment, 129 (30.3%) had serious AEs, and 11 (2.6%) had serious AEs related to treatment. There were 12 deaths (2.8%). Among AEs of interest, epistaxis (22.1%) and telangiectasia (16.9%) were the most frequently reported individual events. Twenty-two (5.2%) participants had serious bleeding events, including 2 (0.5%) with serious bleeding leading to death (not related to treatment by investigator judgment). Improvements in 6MWD, NT-proBNP, WHO FC, and SFRS achieved from baseline of SOTERIA were largely maintained at one year, including in the placebo-crossed group.

Conclusion: Interim results of SOTERIA support the favorable benefit-risk of add-on sotatercept treatment in adults with PAH. Follow-up reports from this study will provide additional information on benefit/risk.