A long-term follow-up study of sotatercept for treatment of pulmonary arterial hypertension: interim results of SOTERIA

Eur Respir J. 2025 Jul 24;66(1):2401435. doi: 10.1183/13993003.01435-2024. Print 2025 Jul.

Abstract

Background: SOTERIA (ClinicalTrials.gov: 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 once every 21 days). Safety and tolerability (primary objective) were assessed by adverse events (AEs), vital signs and laboratory assessments. Efficacy (secondary objective) was assessed by 6-min walk distance (6MWD), N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, World Health Organization (WHO) Functional Class, clinical worsening events and simplified French risk score (SFRS). The data cut-off date was 8 November 2023.

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. 22 (5.2%) participants had serious bleeding events, including two (0.5%) with serious bleeding leading to death (not related to treatment by investigator judgement). Improvements in 6MWD, NT-proBNP, WHO Functional Class and SFRS achieved from baseline of SOTERIA were largely maintained at 1 year, including in the placebo-crossed group.

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

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Female
  • Follow-Up Studies
  • Humans
  • Hypertension, Pulmonary* / drug therapy
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood
  • Peptide Fragments / blood
  • Pulmonary Arterial Hypertension* / drug therapy
  • Recombinant Fusion Proteins* / administration & dosage
  • Recombinant Fusion Proteins* / adverse effects
  • Recombinant Fusion Proteins* / therapeutic use
  • Treatment Outcome
  • Walk Test

Substances

  • Recombinant Fusion Proteins
  • Peptide Fragments
  • Natriuretic Peptide, Brain
  • pro-brain natriuretic peptide (1-76)

Associated data

  • ClinicalTrials.gov/NCT04796337