Efficacy of pitolisant in patients with high burden of narcolepsy symptoms: pooled analysis of short-term, placebo-controlled studies

Study objective: To evaluate the efficacy of pitolisant, a histamine 3 (H3)-receptor antagonist/inverse agonist, in adult patients with high burden of narcolepsy symptoms. Methods: Data were pooled from two randomized, placebo-controlled, 7-or 8-week studies of pitolisant (titrated to a potential maximum dose of 35.6 mg/day) in adults with narcolepsy. Analyses included three independent patient subgroups: Epworth Sleepiness Scale (ESS) baseline score >= 16, Maintenance of Wakefulness Test (MWT) sleep latency <= 8 min, and >= 15 cataplexy attacks per week. Results: The analysis populations included 118 patients for ESS (pitolisant, n = 60; placebo, n = 58), 105 for MWT (pitolisant, n = 59; placebo, n = 46), and 31 for cataplexy (pitolisant, n = 20; placebo, n = 11). On the ESS, least-squares mean change from baseline was significantly greater for pitolisant (-6.1) compared with placebo (-2.3; P < 0.001). Significantly more pitolisant-treated patients were classified as treatment responders: ESS score reduction >= 3, 69.0% in the pitolisant group versus 35.1% in the placebo group (P = 0.001); final ESS score <= 10, 36.2% versus 10.5%, respectively (P = 0.005). On the MWT, mean sleep latency increased from 3.5 min to 10.4 min with pitolisant and from 3.4 min to 6.8 min with placebo (P = 0.017). Least-squares mean change in the weekly rate of cataplexy was significantly greater for pitolisant (-14.5; baseline, 23.9; final, 9.4) compared with placebo (-0.1; baseline, 23.1; final, 23.0; P = 0.004). Headache was the most common adverse event with pitolisant. Conclusions: Pitolisant, at once-daily doses up to 35.6 mg, was efficacious for reducing excessive daytime sleepiness and cataplexy in patients with severe narcolepsy symptom burden. (C) 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

Pitolisant showed efficacy in reducing excessive daytime sleepiness and cataplexy in adult patients, especially those with severe narcolepsy symptoms burden.