Maurice Beghetti, Lene Nygaard Axelsen, Julian I. Borissoff, Mahdi Farhan, Simon Grill, Sining Leng, Alberto Russu, Catherine Lesage, Tatiana Remeňová, Shu-Fang Hsu Schmitz, Shahin Moledina
University Hospitals of Geneva. Johnson & Johnson. Great Ormond Street Hospital.
Switzerland and United Kingdom
Chest
Chest 2025;
DOI: 10.1016/j.chest.2025.12.013
Abstract
Background: Selexipag is an oral selective prostacyclin receptor agonist approved for treating pulmonary arterial hypertension (PAH) in adults.
Research question: What is the starting dose(s) of selexipag needed in patients aged ≥2-<18 years with PAH to achieve exposure comparable to adults (primary objective)?
Study design and methods: In this prospective, multicenter, open-label, single-arm, Phase 2 study (NCT03492177), patients were categorized by age (≥2-<6; ≥6-<12; ≥12-<18 years) and weight (≥9-<25; ≥25-<50; ≥50-kg). Selexipag starting doses (μg b.i.d.) were based on patient bodyweight (≥50-kg, 200; ≥25-<50-kg, 150; and ≥9-<25-kg, 100) and titrated to the individual maximum tolerated dose by week 12. The combined steady-state exposure to selexipag and its metabolite corrected for potency (AUCτ,combined,ss) was assessed during titration. Safety, tolerability, and exploratory efficacy were assessed throughout the study; interim results (data cutoff 29-October-2024) are reported.
Results: Sixty-three patients were enrolled and received selexipag. Most patients were prevalent, female (57%), with either idiopathic PAH (49%) or PAH associated with repaired or coincidental congenital heart disease (43%). The tested dosing regimen in the pediatric population demonstrated similar exposure to that observed in adults; the difference between the estimated and expected AUCτ,ss,combined was <25% in absolute value across age and body weight groups. Over a median 230.3 weeks of treatment, 62 (98.4%) patients experienced ≥1 adverse event (AE) and 33 (52.4%) reported serious AEs. Most common AEs were vomiting (46.0%), headache (39.7%), and diarrhea (36.5%). Eleven (17.5%) deaths were reported, none were considered selexipag-related. Exploratory efficacy findings were consistent with those observed in adults.
Interpretation: These data support using a weight-based dosing regimen of selexipag in patients aged ≥2-<18 years with PAH, reaching similar exposure to adults and being well tolerated. The observed efficacy and safety findings support further evaluation of selexipag in this population.
Category
Class I. Idiopathic Pulmonary Hypertension
Class I. Pulmonary Hypertension Associated with Congenital Cardiovascular Disease
Medical Therapy. Efficacy or Lack of Efficacy
Medical Therapy. Adverse Effects or Lack of Adverse Effects
Medical Therapy. Pharmacokinetics and Pharmacology
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes