Treatment with pitolisant, a potent and highly selective histamine 3 (H3)-receptor antagonist/inverse agonist, reduces excessive daytime sleepiness (EDS) and cataplexy in patients with narcolepsy, according to study results presented at World Sleep 2019, held September 20 to 25, in Vancouver, Canada.
The study was an analysis of the safety and efficacy of the HARMONY-1 and HARMONY-CTP trials, which enrolled patients with narcolepsy who reported excessive daytime sleepiness and cataplexy. In the HARMONY-1 trial, patients were randomly assigned to receive flexible doses of pitolisant (n=32), modafinil (n=33), or placebo (n=30) for an 8-week treatment period.
Patients in the HARMONY-CTP trial were randomly assigned to either pitolisant (n=54) or placebo (n=52) for a total of 7 weeks. The analysis of the 2 trials focused on improvements in excessive daytime sleepiness as assessed by the Epworth Sleepiness Scale as well as improvements in cataplexy as assessed by patient diaries.
Significantly greater improvements in mean Epworth Sleepiness Scale score were observed with pitolisant vs placebo in HARMONY-1 (treatment effect, -3.0; P =.022) and HARMONY-CTP (treatment effect, -3.4; P <.0001). The percentage patients who responded, and had a final scored of <10 on the Epworth Sleepiness Scale, was significantly greater among patients who received pitolisant compared with placebo: HARMONY-1 (45.2% vs 13.3%; P <.001) and HARMONY-CTP (39.2% vs 18.0%; P =.035).
Patients in the HARMONY-1 trial who were receiving pitolisnat experienced a 65% reduction in the daily rate of cataplexy vs 9% reduction among those in the placebo group (rate ratio [RR], 0.38; 95% CI, 0.15‒ 0.93; P =.034). Similarly, patients in the HARMONY-CTP experienced a 75% reduction in the weekly rate of cataplexy from baseline with pitolisant vs a 38% reduction with placebo (estimated RR, 0.51; 95% CI, 0.44‒0.60; P <.001). Headache and nausea were the most common adverse events associated with pitolisant in both trials.
Researchers concluded that these trials demonstrate that a “reduction in the cardinal symptoms of narcolepsy—excessive daytime sleepiness and cataplexy—was significantly greater in patients treated with pitolisant compared with those who received placebo.”
Disclosure: This study was funded and sponsored by Bioprojet Pharma and Harmony Biosciences, LLC. Please see the original reference for a full list of authors’ disclosures.
Dauvilliers Y, Schwartz JC, Davis C, Dayno J, et al. Efficacy and safety of pitolisant in patients with narcolepsy: a review of clinical trials. Abstract presented at World Sleep 2019; September 20-25, 2019; Vancouver, Canada.