0741 Treatment with Pitolisant in Subgroups of Adults with Narcolepsy: Pooled Analysis of Two Randomized Clinical Trials

Abstract Introduction Narcolepsy is a chronic, debilitating neurological disorder of sleep-wake state instability characterized primarily by excessive daytime sleepiness (EDS) and cataplexy. Pitolisant is approved by the US Food and Drug Administration for the treatment of EDS or cataplexy in adult patients with narcolepsy and the treatment of EDS in pediatric patients 6 years of age and older with narcolepsy. The aim of this analysis was to evaluate the effect of pitolisant on EDS in subgroups of adult patients with narcolepsy. Methods Data were pooled from 2 randomized, placebo-controlled, 7- or 8-week studies (HARMONY-1: NCT01067222; HARMONY-CTP: NCT01800045) of pitolisant in adult patients (aged ≥18 years) with narcolepsy. Patients in both studies were required to have EDS at study baseline as measured by the Epworth Sleepiness Scale (ESS) score; in HARMONY-CTP, patients were required to have ≥3 cataplexy attacks/week. Pitolisant was individually titrated over a 3-week period to a maximum dose of 35.6 mg/day; the dose remained stable thereafter. The change in ESS score from baseline to end of treatment was evaluated in different subgroups, which included age (< 30, ≥30 y) and sex (male, female), as well as the following baseline characteristics: body mass index (< 25, 25 to < 30, ≥30 kg/m2), cataplexy severity (none, mild-moderate, severe), use of cataplexy medications (yes/no), renal impairment (none, mild, moderate), and hepatic impairment (none, mild). Results Data from 166 patients (pitolisant, n=85; placebo, n=81) were analyzed. Mean (SD) baseline ESS score was 17.6 (3.0) in the pitolisant group and 17.9 (3.1) in the placebo group. Patients who received pitolisant experienced a greater reduction (improvement) in ESS score than those who received placebo (mean difference [95% CI], -3.44 [-4.83, -2.05]; P< 0.001). The effect of pitolisant on ESS score was similar in most of the subgroups tested (test of interaction, P>0.05), except for hepatic impairment (P=0.04; pitolisant effect greater in patients with mild hepatic impairment). Headache was the most common adverse event in patients treated with pitolisant. Conclusion Pitolisant provides consistent improvements in EDS in a wide range of adult patients with narcolepsy. Support (if any) Harmony Biosciences