505 Efficacy of Pitolisant in the Treatment of Cataplexy in Adults With Narcolepsy

Pitolisant was initially approved by the FDA in 2019 for the treatment of excessive daytime sleepiness in adult patients with narcolepsy; in 2020, the indication was expanded to include the treatment of cataplexy. Methods Cataplexy data from 7- or 8-week, randomized, placebo-controlled studies (HARMONY-CTP, HARMONY-1) are reviewed and summarized. In HARMONY-CTP, all patients were required to have ≥3 cataplexy attacks per week at baseline; HARMONY-1 enrolled patients with narcolepsy with or without cataplexy. Pitolisant was individually titrated to a maximum potential dose of 35.6 mg/day. The weekly (WRC) or daily (DRC) rate of cataplexy attacks was calculated from patient diaries. Results In HARMONY-CTP (pitolisant, n=54; placebo, n=51), mean baseline WRC was 11.7 in the pitolisant group and 9.6 in the placebo group. In the subset of HARMONY-1 patients with cataplexy (pitolisant, n=17; placebo, n=11), mean baseline DRC was 1.5 and 1.2, respectively. In HARMONY-CTP, least-squares (LS) mean change in WRC was significantly greater for pitolisant versus placebo at Week 2 (-4.1 vs 1.2; P=0.004) and continued through end of treatment (Week 7; -6.5 vs -0.1; P<0.001). In HARMONY-CTP, treatment response was observed in 66.7% of pitolisant-treated versus 25.5% of placebo-treated patients (P<0.001) for WRC reduction ≥50%, and 77.8% versus 33.3% of patients (P<0.001) for WRC reduction ≥25%. In HARMONY-1, LS mean change in DRC was significantly greater for pitolisant versus placebo at Week 5 (-1.04 vs 0.17; P=0.047) and continued through end of treatment (Week 8; -0.96 vs 0.35; P=0.035). In a pooled analysis of patients with high burden of cataplexy (≥15 attacks/week) at baseline (pitolisant, n=20; placebo, n=11), LS mean change in WRC at end-of-treatment assessment was significantly greater for pitolisant (-14.5; baseline, 23.9; final, 9.4) versus placebo (-0.1; baseline, 23.1; final, 23.0; P=0.004). There was no evidence of rebound cataplexy after a 1-week placebo washout period. Conclusion Pitolisant, at once-daily doses of up to 35.6 mg, demonstrated a statistically significant and clinically meaningful reduction in the frequency of cataplexy attacks in adults with narcolepsy, including patients with a high symptom burden. Onset of response was observed within the first few weeks of pitolisant treatment. Support (if any) Bioprojet Pharma and Harmony Biosciences, LLC.