Sotatercept in Pediatric Pulmonary Hypertension: Experience from the Pediatric Pulmonary Hypertension Network.

Abstract

Background: Sotatercept, a ligand trap for TGF-β family members, has been shown to improve exercise capacity and decrease pulmonary vascular resistance (PVR) in adults with pulmonary arterial hypertension. Limited data exist describing the use of sotatercept in children with pulmonary hypertension (PH).

Research question: What is the safety and efficacy of sotatercept as add-on therapy in children with PH.

Study design and methods: This is a multi-center, retrospective study of children and young adults ≤ 21 years of age with pediatric PH treated by programs in the Pediatric PH Network and institutional registries. Demographic data and clinical characteristics before and after sotatercept initiation were collected.

Results: Sixty-six subjects received sotatercept as add-on therapy for a median duration of 323 days (Interquartile range 239, 500). Forty (60%) were female with median age 15.3 years (range 3.0 - 21.0) at initiation of sotatercept, and 61 with Group 1 (92%) PH. WHO functional class improved in 51% and did not worsen in any subjects (p < 0.0001). Subjects experienced significant improvement in six-minute walk distance (median 31 m, p=0.0003, n=40), NT-proBNP (median decrease 378 pg/ml, p< 0.0001, n=26), mean pulmonary artery pressure (median decrease 17 mmHg, p<0.0001, n=21), and PVR (median decrease 4.4 WUi, p=0.0011, n=21). Parenteral prostacyclin was weaned or discontinued in 13 of 38 patients. Adverse events occurred in 33 (50%) subjects with bleeding in 15 (23%). No patients had escalation of PH therapy, were hospitalized for clinical worsening, underwent lung transplant, or died.

Interpretation: Pediatric PH patients treated with sotatercept as add-on therapy demonstrated improvement in functional class and other PH disease indicators and was generally well tolerated.