CLINICAL IMPACT OF PITOLISANT ON EXCESSIVE DAYTIME SLEEPINESS AND CATAPLEXY IN ADULTS WITH HIGH BURDEN OF NARCOLEPSY SYMPTOMS

Abstract Introduction This post hoc analysis evaluated the clinical impact of pitolisant for the reduction of excessive daytime sleepiness (EDS) and cataplexy in adults with a high burden of narcolepsy symptoms. When evaluating results of randomized, placebo-controlled trials, the clinical impact of a treatment can be assessed using effect size metrics that include Cohen’s d (the standardized mean difference of an effect) and number needed to treat (NNT; number of patients that need to be treated to achieve a specific outcome for one person). Methods Data were pooled from 2 randomized, placebo-controlled, 7- and 8-week studies of pitolisant (individually titrated; potential maximum dose, 35.6 mg/day) in adults with narcolepsy. Analyses included 3 independent patient subgroups with high symptom burden: (1) baseline score of ≥16 on the Epworth Sleepiness Scale (ESS), (2) sleep latency of ≤8 minutes on the Maintenance of Wakefulness Test (MWT), and (3) ≥15 cataplexy attacks per week. Efficacy measures included the ESS, MWT, weekly rate of cataplexy (WRC), and Clinical Global Impression of Change (CGI-C). Cohen’s d was derived from the least-squares mean difference between treatment groups (pitolisant vs placebo), and NNTs were calculated from response rates. Missing values were imputed using a last observation carried forward approach. Results The high-burden populations included 118 patients for the ESS subgroup (pitolisant, n=60; placebo, n=58), 105 for MWT (pitolisant, n=59; placebo, n=46), and 31 for cataplexy (pitolisant, n=20; placebo, n=11). Cohen’s d effect size values for pitolisant versus placebo were 0.80 for ESS, 0.31 for MWT, and 1.31 for WRC. NNTs for pitolisant were 3 for ESS score reduction (≥3-point decrease from baseline or final score ≤10) in the ESS subgroup and 2 for WRC reduction (≥50% decrease from baseline) in the cataplexy subgroup. For the CGI-C for EDS (“much” or “very much” improved), NNT was 5 in the ESS subgroup and 4 in the MWT subgroup; for the CGI-C for cataplexy, NNT was 3 in the cataplexy subgroup. Conclusion The results of this analysis demonstrate the robust efficacy of pitolisant for the reduction of both EDS and cataplexy in patients with severe narcolepsy symptom burden. Support (If Any) Bioprojet Pharma and Harmony Biosciences, LLC.