A phase 2 clinical trial evaluating a weight-based dose regimen of Uptravi (selexipag) for children with pulmonary arterial hypertension (PAH) has demonstrated similar drug exposure to that of the standard adult dose regimen. Results of the study, “A Prospective, Multicenter, Open-Label, Single-Arm Phase 2 Study to Investigate the Pharmacokinetics, Safety, Tolerability and Exploratory Efficacy of Selexipag in Children With Pulmonary Arterial Hypertension,” were published in Chest.
The primary endpoint of the study was to identify a dosing schedule of Uptravi for pediatric patients aged two to 18 years old that achieved levels of the drug’s active ingredient comparable to adult patients in the GRIPHON study. Based on results of the GRIPHON study, which showed significant reduction in the risk of disease progression in oral therapy versus placebo, Uptravi received FDA approval to treat adults with PAH.
Researchers in the phase 2 pediatric trial also observed comparable safety and efficacy in the weight-based Uptravi regimen similar to that in adults. The study included 63 children with PAH, in which majority were female and white. Participants either had PAH caused by a complication of congenital heart disease or idiopathic PAH with no known cause of disease.
Individuals were split into three groups based on body weight:
- Children weighing less than 55 lbs (25 kg) received a starting dose of 100 mcg twice daily, increased to a maximum of 800 mcg as tolerated.
- Children weighing 55–110 lbs (25-50 kg) received a starting dose of 150 mcg twice daily, increased to a maximum of 1,200 mcg as tolerated.
- Children weighing more than 110 lbs (50 kg) received a starting dose of 200 mcg twice daily, increased to a maximum of 1,600 mcg as tolerated.
Minor adverse events occurred in approximately 75% of pediatric patients and mirrored those of adults. The most common side effects were headache, vomiting and diarrhea. No unexpected safety issues were reported.
Currently, there are limited approved therapeutic options for pediatric PAH in the United States and Europe. Researchers are working to establish the risk-benefit ratio of Uptravi in children. In the meantime, drug developer Johnson & Johnson urges physicians to use discretion in administering treatment.
Johnson & Johnson said it expects the phase 2 clinical trial to be completed in late 2026. Its phase 3 SALTO trial is an ongoing randomized, multicenter, double-blind, placebo-controlled, parallel-group study assessing the efficacy and safety of the weight-based Uptravi regimen as an add-on treatment to standard of care in children with PAH.
