Abstract Background Sotatercept, a first-in-class activin signalling inhibitor, has recently emerged as an add-on therapy for pulmonary arterial hypertension (PAH). In France, an early access program was initiated for patients with severe PAH receiving background triple therapy including parenteral prostacyclin. We report here the first nationwide real-world data from this program. Methods Between June 2024 and January 2025, 101 patients with all cause of PAH except portopulmonary hypertension and non-repaired congenital heart disease were enrolled in the early access program across 19 participating expert centres. Baseline clinical, functional and hemodynamic data, and background therapy were collected at sotatercept initiation. Changes in hemodynamics, six-minute walk distance (6MWD), and risk status according to the ESC-ERS 4-strata methodology were assessed during follow-up. Results At sotatercept initiation, all patients received triple therapy combining an endothelin receptor antagonist, a PDE-5 inhibitor (or guanylate cyclase stimulator), and a parenteral prostacyclin (64% IV, 36% SC). The median time from PAH diagnosis to sotatercept initiation was 6.8 years (IQR 3.7-12.4). Baseline mean PAP was 50±12 mmHg, pulmonary vascular resistance (PVR) 8.1±3.5 WU, cardiac index 3.1±0.8 L/min/m², and 6MWD 443±163 m. The mean follow-up duration was 12.6 ± 3.0 months. During follow-up, 4 patients died and 2 underwent lung transplantation. After a 6-month follow-up, the median change in 6MWD was +17 m (IQR -3-339). Fourty-three percent of patients remained stable at low risk, 35% improved, 15% were stable but not at low risk, and 6% worsened. Hemodynamics was reassessed in 68 patients and showed significant improvements, with a mean reduction in PVR of 2.0±2.4 WU ( -26%). Weaning from parenteral prostacyclin was achieved in 23 patients (23%), after a mean of 8.1 ± 2.6 months of sotatercept treatment. Sixteen patients (16%) discontinued sotatercept after a mean of 6.3 ± 2.9 months. Adverse events included bleeding in 11%, pericardial effusion in 3%, and hypoxemia related to intrapulmonary shunt in 1%. Conclusions This real-world experience confirms the clinical benefit of sotatercept in PAH on background triple therapy including parenteral prostacyclin. Improvements in exercise capacity, hemodynamics, and risk profile, along with prostacyclin weaning in nearly one-quarter of patients, support its therapeutic value. This abstract is funded by: None
Montani et al. (Fri,) studied this question.