0768 Time Course Of Improvement In Excessive Daytime Sleepiness And Cataplexy During Treatment With Pitolisant In Patients With Narcolepsy

Abstract

Abstract Introduction This analysis evaluated the efficacy of pitolisant over time in three 7- to 8-week, randomized, placebo-controlled studies of adults with narcolepsy. Methods Patients in all 3 studies (HARMONY-1, HARMONY-1bis, HARMONY-CTP) experienced excessive daytime sleepiness (EDS) at study baseline; patients in HARMONY-CTP also experienced ≥3 cataplexy attacks/week. Pitolisant was titrated to a maximum dose of 35.6 mg/day (HARMONY-1, HARMONY-CTP) or 17.8 mg/day (HARMONY-1bis). Change from baseline in mean Epworth Sleepiness Scale (ESS) score (3 studies) and mean weekly rate of cataplexy (WRC; 1 study) was compared for pitolisant versus placebo. Results In the higher-dose HARMONY-1 (pitolisant, n=31; placebo, n=30) and HARMONY-CTP (pitolisant, n=54; placebo, n=51) studies, ESS score improvement was significantly greater with pitolisant versus placebo beginning at Week 2 (LS mean difference, -2.8; P=0.015) and Week 3 (LS mean difference, -2.0; P=0.005), respectively. In the lower-dose HARMONY-1bis study (pitolisant, n=66; placebo, n=32), significant separation from placebo was first observed at Week 7 (LS mean difference, -2.3; P=0.044). At end-of-treatment, LS mean difference in ESS score change from baseline was -3.1 (P=0.022) in HARMONY-1, -3.4 (P<0.001) in HARMONY-CTP, and -2.2 (P=0.030) in HARMONY-1bis. In HARMONY-CTP, LS mean 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 WRC was significantly greater with pitolisant versus placebo beginning at Week 2 (LS mean difference, -5.3; P=0.004) and continued through end-of-treatment (LS mean difference, -6.2; P<0.001); there was no evidence of rebound cataplexy after placebo-washout (LS mean difference, -4.9; P=0.027). Conclusion During pitolisant treatment, improvement in EDS occurred sooner (within first few weeks) and was more robust in studies that permitted titration to the maximum recommended dose (35.6 mg/day). The rate of cataplexy attacks decreased early during treatment, with no evidence of rebound when pitolisant was withdrawn. Support Bioprojet Pharma and Harmony Biosciences, LLC.