0866 Effect of Pitolisant on Idiopathic Hypersomnia Symptoms During a Double-Blind Withdrawal Period in a Phase 3 Trial

Introduction Pitolisant is FDA approved for the treatment of excessive daytime sleepiness (EDS) or cataplexy in adult patients with narcolepsy and for the treatment of EDS in pediatric patients ≥6 years with narcolepsy. Given the adjacency between IH and narcolepsy and pharmacological treatments for IH are limited, the efficacy of pitolisant is being evaluated in adult patients with IH. Methods The present analyses focused on a 4-week double-blind randomized withdrawal period (DBRWP) within a 12-week phase 3 clinical trial to evaluate the safety and efficacy of pitolisant in adult patients with IH (NCT05156047). Patients (213) initially received pitolisant for an 8-week open-label period (OLP) and then were assessed for their treatment response. Treatment responders (≥3-point reduction in their Epworth Sleepiness Scale [ESS] scores across the OLP) entered the DBRWP and were randomized to continue receiving dose-matched pitolisant or placebo. Primary and key-secondary efficacy measures included the ESS and the Idiopathic Hypersomnia Severity Scale (IHSS), respectively; change scores were evaluated from the end of the OLP to the end of the 4-week DBRWP for pitolisant compared with placebo. Results Among the 173/213 patients who completed the OLP (81.2%), 139 (80.3%) of them were considered treatment responders and entered the DBRWP (mean±SD age: 39.9±11.91 years; 78.6% female). During the DBRWP the LSM difference (95% CI) in total score between the pitolisant and placebo treatment groups was not statistically significant for the ESS (-0.85 [-2.24, 0.54]; P=0.228) and narrowly missed nominal statistical significance for the IHSS (-2.27 [-4.62, 0.08]; P=0.058). When statistically adjusting for the suspected placebo effect and suspected regression to the mean, there was a nominally statistically significant difference between pitolisant and placebo on the ESS (-1.51 [-2.84, -0.18] P=0.026) and the IHSS (-3.20 [-5.49, -0.90] P=0.006). No new safety signals were observed. Conclusion During the 4-week DBRWP, positive trends favoring pitolisant were observed on the ESS and IHSS; however, they did not reach prespecified statistical significance. Ad hoc analyses showed nominally statistically significant improvements in ESS and IHSS. Pitolisant may offer a favorable benefit-risk profile and could be a potential treatment option for patients with IH. Support (if any)