Pitolisant Delivers Clinical Improvements as Early as 2 Weeks After Starting Treatment
Post-hoc analysis of the HARMONY-1 and HARMONY-CTP clinical trials (NCT01067222, NCT01800045) showed treatment with pitolisant (Wakix; Harmony Biosciences, Plymouth Meeting, PA) had clinical effects as early as the second week of treatment. Dosing of pitolisant begins at 8.9 mg/day and is titrated to 35.6 mg/day over 3 weeks by doubling the dose each week.
In the HARMONY-CTP trial the average rate of cataplexy before treatment was 11.7/week and improved to 4.66/week at the end-of-treatment. Improvement in weekly rate of cataplexy was significantly greater with pitolisant versus placebo beginning at Week 2 (least squares mean [LSM] difference, 5.3) and continued through end-of-treatment (LSM difference, -6.4). No evidence of rebound cataplexy was observed after placebo-washout.
Excessive daytime sleepiness (EDS), as measured by the Epworth Sleepiness Scale (ESS), also improved in weeks 2 and 3 of treatment. Participants in HARMONY-1 who were treated with pitolisant had a 2.8-point improvement vs placebo on the 24-point ESS in week 2 of treatment. Participants in HARMONY-CTP had a 2.0-point improvement vs placebo on ESS at week 3 of treatment. Response rates continued to improve in both trials, and the final change in EDS vs placebo were 3.2 and 4.0 points, respectively.
“The most important aspect of the data Harmony is presenting at AAN this year is that it drills down a little deeper into the pivotal data from the clinical development program in order to shed more light on the clinical relevance of WAKIX,” said Harmony’s Chief Medical Officer, Jeffrey Dayno, MD “The poster on the post-hoc analysis of the time to onset of a clinical response shows that pitolisant separated from placebo beginning at week 2 for both the symptoms of EDS and cataplexy. Therefore, although it may take up to 8 weeks for some patients to experience a clinical response to WAKIX, this analysis shows that others may experience an improvement in EDS and cataplexy sooner than that,” said Dayno. “It is also important for healthcare professionals to provide an adequate therapeutic trial when treating patients with a chronic, life-long disorder like narcolepsy.”
Pooled analysis of data from HARMONY-1 and HARMONY CTP showed no statistically significant differences in heart rate, systolic or diastolic blood pressure, or QTc interval in those treated with pitolisant vs placebo. In the long-term study, however, mean change QTc interval change was an increase of 3.1 milliseconds after 6 months of treatment and 6.1 milliseconds after 12 months of treatment. In pharmacokinetic studies in healthy volunteers, the recommended dose of 35.6 mg/day of pitolisant increased QTc interval by a mean 4.2 seconds. Pitolisant prescribing information includes a warning that pitolisant use should be avoided in people with risk factors for prolonged QT interval and should not be used with other medications known to prolong the QT interval.
The HARMONY-1 and HARMONY CTP trials were double-blind randomized placebo-controlled studies and the results reported here all reached statistical significance on post-hoc analysis. These data were reported at the American Academy of Neurology's 21st Annual Meeting held online April 17-22, 2021.