Pitolisant Treatment Improves Multiple Clinical Symptoms of Prader-Willi Syndrome (PWS) in Children

Objective: We hypothesized that pitolisant could improve sleepiness and quality of life in children with PWS and tracked patient experience data with pitolisant. Background: The European Medicines Agency (EMA) approved pitolisant (Wakix®, Bioprojet Pharma, Paris, France) as a first-in-class histamine H3 receptor inverse agonist for the treatment of the rare disease narcolepsy with or without cataplexy (2016). Pitolisant is being considered by the FDA for the same indication. Prader-Willi Syndrome (PWS) is frequently identified by its hallmark symptoms of obesity and hyperphagia. Our analysis of discussion in a closed PWS group on social media revealed, however, that caregivers used terms for “sleepiness” more often than they used terms for “hunger.” These results are consistent with a previous PWS survey which identified hypotonia, intellectual disability and sleep issues as more common than hyperphagia and obesity. Design/Methods: Our database includes ten children (ages 2–16) in the United States who have obtained pitolisant from Europe via personal importation allowed at the FDA’s discretion. The families agreed to document their experience on the TREND Community platform, some for more than two years. Dosing for children with PWS (4.5 – 31 mg/day) is, in many cases, higher than the 18 mg tested in European clinical trials of children with narcolepsy. All children with PWS started with the lowest possible dose of 4.5 mg/day and increased the dose gradually, as necessary, to combat excessive daytime sleepiness. Results: The children experienced decreased daytime sleepiness, improved night time sleep, as well as improved cognition as evidenced by increased processing speed and improved mental clarity. Conclusions: The promising patient-reported experience suggests that pitolisant may represent a novel therapeutic option to relieve substantial PWS disease burden. The results also suggest that patients with PWS exhibit many of the same symptoms as narcolepsy with cataplexy and may benefit from consultation with a neurologist. Disclosure: Dr. Pullen has nothing to disclose. Dr. Picone has received research support from Harmony Biosciences. Dr. Tan has nothing to disclose. Dr. Johnston has nothing to disclose. Dr. Stark has received royalty, license fees, or contractual rights payments from Bioprojet.