Introduction: Sotatercept is a first-in-class activin signaling inhibitor under study for PAH. In the phase 2 PULSAR and phase 3 STELLAR trials, sotatercept added to standard PAH therapy significantly improved functional and hemodynamic parameters.

Objectives: To assess the long-term safety/tolerability (primary) and efficacy (secondary) of sotatercept.

Methods: SOTERIA is an LTFU study (NCT04796337) wherein adults with PAH who completed prior sotatercept trials receive open-label sotatercept (0.3 or 0.7 mg/kg Q3W) on background PAH therapy for up to 4 years. Safety/tolerability are assessed by adverse events (AEs), and efficacy by 6-min walk distance (6MWD), N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, WHO functional class (FC), clinical worsening events, and French risk score (FRS). Cumulative data cutoff date was 04/20/2023.

Results: As of the cutoff date, 409 patients have enrolled in SOTERIA. Median duration of exposure to sotatercept was 336.0 days (range 21-1072 days). Improvements in 6MWD, NT-proBNP, WHO FC, and FRS were maintained at 1 year during the open-label observation period. Seven participants had 9 clinical worsening events, including 3 deaths and 3 PAH-related hospitalizations. Ninety-three participants (23%) had telangiectasia (none were serious), including 51 (12%) who developed this AE during a prior trial. Two dose holds and 2 dose reductions occurred due to telangiectasia.

Conclusion: These results support the long-term durable clinical benefit and safety of sotatercept treatment in patients with PAH.