0762 Efficacy Of Pitolisant In Patients With High Burden Of Narcolepsy Symptoms. (27th May 2020)

• Record Type: Journal Article
• Authors: Davis, C W; Kallweit, U; Krahn, L E; Vaughn, B; Thorpy, M J
• Is Part Of: Sleep. Volume 43(2020)Supplement 1
• Page Start: A289
• Page End: A290
• Publication Date: 2020-05-27
• Subjects: Sleep -- Physiological aspects -- Periodicals; Sleep disorders -- Periodicals; Sommeil -- Aspect physiologique -- Périodiques; Sommeil, Troubles du -- Périodiques; Sleep disorders; Sleep -- Physiological aspects; Sleep -- physiological aspects; Sleep Wake Disorders; Psychophysiology; Electronic journals; Periodicals; 616.8498
• DOI: 10.1093/sleep/zsaa056.758
• Languages: English
• ISSNs: 0161-8105

Abstract

Abstract: Introduction: Recent literature suggests that histamine may play an important role in narcolepsy. This post hoc analysis evaluates the efficacy of pitolisant, a histamine 3 (H3 )-receptor antagonist/inverse agonist, in patients with high burden of the main narcolepsy symptoms. Methods: Data were pooled from 2 randomized, placebo-controlled, 7- and 8-week studies of pitolisant (individually titrated; maximum dose, 35.6 mg/day) in adults with narcolepsy. Analyses included 3 independent patient subgroups: baseline score of >16 on the Epworth Sleepiness Scale (ESS), sleep latency of ≤8 minutes on the Maintenance of Wakefulness Test (MWT), and ≥15 cataplexy attacks per week. Results: The analysis populations included 108 patients for the ESS (pitolisant, n=54; placebo, n=54), 105 for the MWT (pitolisant, n=59; placebo, n=46), and 31 for cataplexy (pitolisant, n=20; placebo, n=11). Mean change in ESS from baseline was significantly greater for pitolisant (-6.1) compared with placebo (-2.6; P =0.0002). A significantly greater percentage of pitolisant-treated patients were classified as treatment responders: for ESS score reduction ≥3, 68.5% in the pitolisant group versus 35.2% in the placebo group ( P =0.0006); for final ESS score ≤10, 35.2% versus 9.3%, respectively ( P =0.0026). Mean increase in sleep latency on the MWT was significantly greater for pitolisant (7.0 minutes) compared with placebo (3.4 minutes; P =0.0089). Decrease in mean weekly rate of cataplexy was significantly greater for pitolisant (baseline, 21.8; final, 3.9) compared with placebo (baseline, 20.9; final, 18.2); the rate ratio was 0.35 (95% CI, 0.26‒0.47; P <0.001). The adverse event profile in the analysis populations was consistent with the known safety profile for pitolisant; headache was the most common adverse event in pitolisant-treated patients (10.0%-20.4%). Conclusion: In patients with severe symptom burden, pitolisant produced significantly greater improvements in excessive daytime sleepiness and cataplexy compared with placebo, highlighting the important role of histamine in narcolepsy. Support: Bioprojet Pharma and Harmony Biosciences, LLC.