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 ≥ 2 to < 18 years of age with PAH to achieve exposure comparable with 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 to < 6, ≥ 6 to < 12, and ≥ 12 to < 18 years) and weight (≥ 9 to < 25, ≥ 25 to < 50, and ≥ 50 kg). Selexipag starting doses were based on patient body weight (≥ 50 kg: 200 μg bid; ≥ 25 to < 50 kg: 150 μg bid; and ≥ 9 to < 25 kg: 100 μg bid) and titrated to the individual maximum tolerated dose by week 12. The combined steady-state exposure to selexipag and its metabolite corrected for potency was assessed during titration. Safety, tolerability, and exploratory efficacy were assessed throughout the study; interim results (data cut off October 29, 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 combined area under the plasma concentration-time curve over 1 dosing interval at steady state was < 25% in absolute value across age and body weight groups. Over a median of 230.3 weeks of treatment, 62 patients (98.4%) 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 ≥ 2 to <18 years of age 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.

Clinical trial registration: ClinicalTrials.gov; No.: NCT03492177; URL: www.

Clinicaltrials: gov.