Abstract Details

Title Efficacy of Pitolisant in Patients With High Burden of Narcolepsy Symptoms

Topic Sleep

Presentation(s) P3 - Poster Session 3 (12:00 PM-1:00 PM)

Poster/Presentation
Number 5-003

Objective To evaluate the efficacy of pitolisant in patients with high burden of narcolepsy symptoms.

Background Recent literature suggests that histamine may play an important role in narcolepsy. Pitolisant, a histamine 3 (H₃)-receptor antagonist/inverse agonist, increases histaminergic transmission in the brain.

Design/Methods Data were pooled from 2 randomized, placebo-controlled, 7- and 8-week studies of pitolisant (individually titrated to a maximum dose of 35.6 g/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 patients for the MWT (pitolisant, n=59; placebo, n=46), and 31 patients 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 in the pitolisant group (baseline, 21.8; final, 3.9) versus the placebo group (baseline, 20.9; final, 18.2); the rate ratio was 0.35 (95% confidence interval, 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.

Conclusions In patients with severe symptom burden, pitolisant produced significantly greater improvements in excessive daytime sleepiness and cataplexy compared with placebo, further supporting the important role of histamine in narcolepsy.

Authors/Disclosures
Craig Davis, PhD (Harmony Biosciences) PRESENTER	Dr. Davis has received personal compensation for serving as an employee of Harmony Biosciences. Dr. Davis has received stock or an ownership interest from Harmony Biosciences.
Lois Krahn	Lois Krahn has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avadel. Lois Krahn has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Takeda. Lois Krahn has received personal compensation in the range of $500-$4,999 for serving as an officer or member of the Board of Directors for Arizona Medical Board. The institution of Lois Krahn has received research support from Takeda. Lois Krahn has received publishing royalties from a publication relating to health care.
	No disclosure on file
Michael J. Thorpy, MD (Montefiore Medical Center)	Dr. Thorpy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Jazz. Dr. Thorpy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avadel. Dr. Thorpy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for alkermes. Dr. Thorpy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Harmony. Dr. Thorpy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for centessa. Dr. Thorpy has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Axsome. Dr. Thorpy has received publishing royalties from a publication relating to health care.

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