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

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.

Overview of the SOTERIA study. ^#: start date on or after the first dose of treatment and up to 8 weeks after the last treatment dose; ^¶: in the opinion of the investigator; ⁺: serious bleeding is a subcategory of serious treatment-emergent adverse events (TEAEs) of interest (TEAEs of interest were predefined parameters that were monitored to assess the overall safety profile of sotatercept); ^§: telangiectasia was a prespecified TEAE of special interest; ^ƒ: includes participants who developed telangiectasia in this study after rollover; ^##: low simplified French risk score was defined as the presence of three low-risk criteria: World Health Organization Functional Class (WHO FC) I/II, 6-min walk distance (6MWD) >440 m and N-terminal pro-brain natriuretic peptide (NT-proBNP) <300 pg·mL⁻¹. PAH: pulmonary arterial hypertension. *: p<0.0001.

FIGURE 1

Time from first dose in SOTERIA to the onset of telangiectasia.

FIGURE 2

Box plots of a) 6-min walk distance (6MWD) and b) N-terminal pro-brain natriuretic peptide (NT-proBNP) at baseline, Week 24 and Year 1 of sotatercept treatment in SOTERIA for the placebo-crossed and continued-sotatercept groups. Baseline is defined as either the end-of-treatment assessment from the parent study or the Visit 1 assessment in this study, depending on the parameter and data availability. See supplementary figure S4 for box plots for the blinded and total groups. a) 6MWD box plots are displayed on a linear scale. b) NT-proBNP box plots are displayed on a log₁₀ scale due to high variability in values (see supplementary figure S6 for linear scale box plots). p-values are for change from baseline. *: p<0.0001.

FIGURE 3

Proportions of participants categorised according to a) World Health Organization Functional Class (WHO FC) and b) low simplified French risk score (SFRS) at baseline, Week 24 and Year 1. “Yes”: participants met all three criteria for low SFRS (WHO FC I/II, 6-min walk distance >440 m and N-terminal pro-brain natriuretic peptide <300 pg·mL⁻¹); “No”: participants did not meet all three criteria. See supplementary figure S6 for bar charts for the blinded and total groups.