Three post-hoc analyses of the efficacy and safety data for pitolisant (WAKIX; Harmony Biosciences Holding, Plymouth Meeting, PA) showed improvement in excessive daytime sleepiness (EDS) and reduction in cataplexy occurred with pitolisant vs placebo treatment.
In 2 studies, Harmony 1 (NCT01067222) and Harmony CTP (NCT01800045), pitolisant was gradually increased and adjusted to a maximum dose of 35.6 mg/day. In both studies, the average change from the baseline Epworth Sleepiness Scale (ESS) scores and average weekly rate of cataplexy (WRC) was compared for participants treated with pitolisant vs placebo.
In the Harmony 1 (pitolisant, n=31; placebo, n=30) and Harmony CTP (pitolisant, n=54; placebo, n=51) trials, the ESS score improvement was significantly greater with pitolisant vs placebo treatment by the beginning of week 2 (least square [LS] average difference, -2.8; P=.015) and was maintained through week 3 (LS average difference, -2.0; P=.005).
In Harmony CTP, the LS average WRC with pitolisant was 11.7 at baseline, 4.6 at end of treatment, and 5.1 after a 1-week placebo-washout period. Improvement in the WRC was significantly greater with pitolisant vs placebo beginning at week 2 (LS average difference, -5.3; P=.004) and continued through the end of treatment (LS average difference, -6.2; P<.001). There were no signs of cataplexy coming back after the placebo-washout (LS average difference, -4.9; P=.027).
The third post-hoc analysis examined the efficacy of pitolisant in participants with narcolepsy and high symptoms of EDS and cataplexy at baseline. The analyses included 3 participants subgroups: 1) baseline score of less than16 on the ESS (pitolisant, n=54; placebo, n=54); 2) sleep latency of 8 minutes or more on the MWT (pitolisant, n=59; placebo, n=46); and 3) 15 or less cataplexy attacks per week (pitolisant, n=20; placebo, n=11).
For all 3 groups, the average change in ESS from baseline was -6.1 with pitolisant compared with -2.6 with placebo treatment (P=.0002). Of those treated with pitolisant, 68.5% had a reduction of at least 3 points on the ESS vs 35.2% of those treated with placebo (P=.0006). The average increase in sleep latency on the maintenance of wakefulness test (MWT) was 7.0 minutes with pitolisant treatment compared with 3.4 minutes with placebo treatment (P=.0089). Decrease in the average WRC was -17.9 with pitolisant treatment vs -2.7 with placebo, a rate ratio of 0.35 (95% CI, 0.26-0.47; P<.001).
Danielle S. Shpiner, MD; Crystal Dixon, MD; Melissa R. Ortega, MD; and Henry Moore, MD
F. Stephen Benesh, MD, and Shruti P. Agnihotri, MD
James Geyer, MD, and Paul Cox