0577 Clinically Meaningful Improvements With Pitolisant in Adults With Narcolepsy: Pooled Analysis of Randomized Clinical Trials

Abstract

Abstract Introduction Narcolepsy is characterized by symptoms indicative of sleep–wake dysregulation, notably excessive daytime sleepiness (EDS) and cataplexy. In 2021, the American Academy of Sleep Medicine (AASM) updated its clinical practice guidelines on the treatment of central disorders of hypersomnolence. The AASM identified clinical significance thresholds (CSTs) of a 2-point reduction in Epworth Sleepiness Scale (ESS) score and a 25% reduction in the frequency of cataplexy, amongst others, to compare posttreatment effects between intervention and placebo. This post hoc analysis evaluates the efficacy of pitolisant in the treatment of patients with narcolepsy using these updated CSTs. Methods Data were pooled from 2 randomized, placebo-controlled, 7- and 8-week studies (HARMONY-1, HARMONY-CTP) of pitolisant in adults with narcolepsy. Pitolisant was individually titrated over a 3-week period (maximum potential dose, 35.6 mg/day), and the dose remained stable thereafter. The analysis population for EDS included all patients who received pitolisant or placebo (ESS score ≥12 required for study inclusion). The analysis population for cataplexy included treated patients who experienced ≥3 attacks per week at baseline. The end-of-treatment value for the ESS was the score at the last study visit (last observation carried forward [LOCF]). The cataplexy endpoint was the weekly rate of cataplexy (WRC) during the stable dose period (LOCF). Results Data from 166 patients for EDS (pitolisant, n=85; placebo, n=81) and 122 patients for cataplexy (pitolisant, n=64; placebo, n=58) 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. Mean (SD) baseline WRC was 12.4 (10.7) and 9.9 (9.0), respectively. At the end of treatment, ESS score reduction of ≥2 points was observed in a significantly greater percentage of patients in the pitolisant group (72.9%) as compared with the placebo group (45.7%; P< 0.001). The percentage of patients with a reduction in WRC of ≥25% was significantly greater with pitolisant (78.1%) versus placebo (34.5%, P< 0.001). Conclusion Pitolisant provides statistically significant and clinically meaningful reductions in EDS and cataplexy in patients with narcolepsy, based upon the CSTs associated with the updated AASM clinical practice guidelines. Support (if any) Bioprojet Pharma and Harmony Biosciences, LLC.