B67-09 Real-world Impact of Sotatercept on Clinical and Hemodynamic Outcomes in Pulmonary Arterial Hypertension

Introduction Pulmonary arterial hypertension (PAH) is a progressive disease that often requires combination therapy at maximally tolerated doses. Since receiving FDA approval in March 2024, sotatercept has been used in real-world clinical settings, potentially in populations different from those in clinical trials. We describe our experience with sotatercept and its impact on clinical, hemodynamic, and biomarker parameters in PAH patients Methods Eighty-nine PAH patients who received their first dose of sotatercept between 2024 and 2025 were identified from the pulmonary hypertension comprehensive care center at the Houston Methodist Lung center. Demographics, clinical, and hemodynamic data including age, gender, six-minute walk distance (6MWD), right atrial pressure (RAP), pulmonary vascular resistance (PVR), NT-proBNP and echocardiographic evidence of pericardial effusion (PE) were collected. Pre- and post-treatment values were defined as the most recent assessment prior to sotatercept initiation and at follow-up visit. Patients receiving >4 doses were included. COMPERA 2.0 risk scores were calculated at both timepoints. Data are presented as mean±SD or median [IQR] as appropriate. N= number of patients. Paired t-tests or Wilcoxon signed-rank tests were used, with P < 0.05 considered significant. Results Median age was 60 years [IQR 48-73], 88% were female. Common PAH etiologies were connective tissue disease-associated (42%), idiopathic (26%), drug/toxin associated (18%) and congenital heart disease-associated (14%). Median PAH duration prior to sotatercept initiation was 5 years (IQR 2-10); Median number of sotatercept doses was 5 (mean 4.3); 75% completed all five scheduled doses. Among 41 patients with paired 6MWD data, mean increased from 359 ± 124 m to 376 ± 129 m (Δ = +17 ± 45 m, P = 0.02). Hemodynamic improved: PVR decreased from 8.5±4.3 to 6.2±2.9 Wood Unit (Δ = -2.3±5.0, P = 0.02), and mRAP from 8.0 [6.0] to 7.0 [5.0] mm Hg (P = 0.047). NT-proBNP levels decreased from 813 [1611] to 334 [949] pg/mL (N = 78; -154.0 [658.0], P < 0.001). COMPERA 2.0 score improved from 2.4±1.0 to 2.2±1.0 (P < 0.01). Hemoglobin increased from 12.4 [2.6] to 13.5 [2.7] g/dL (N = 83, P < 0.001). Echocardiography (N = 71) reported no PE (53.5%), new PE (12.7%), resolution of PE (12.7%) and unchanged PE (21%). Conclusion Sotatercept was associated with significant improvement in pulmonary hemodynamics, biomarker levels and walk distances, and a shift towards lower risk status supporting its clinical benefit in a real-world setting. This abstract is funded by: none