Pitolisant as a Novel First-in-Class Treatment for Narcolepsy
June 18, 2018
Baltimore, Maryland –Harmony Biosciences recently received Breakthrough Therapy and Fast Track designation from the FDA. Last week they presented two posters at SLEEP 2018, the premier world forum for the presentation and discussion of the latest developments in clinical sleep medicine and sleep and circadian science. Their two posters described pitolisant as a novel first-in-class treatment option for patients with narcolepsy.
In the first poster, Yves Dauvilliers, MD, PhD Professor of Neurology at the University of Montpellier in France and colleagues present continued results from the Harmony 3 study which was a randomized, placebo-controlled study of pitolisant as a treatment for patients diagnosed with narcolepsy with or without cataplexy. The study now includes 73 de novo patients and 29 previously treated patients. Approximately two thirds of patients in the study completed more than 12 months of treatment with approximately 10% of patients withdrawing because of adverse events and 20% withdrawing because of perceived lack of efficacy. Most of the patients who discontinued participation in the study did so within the first three months of treatment.
The mean duration of treatment was 342 days overall (260 days in the de novo population and 548 days for previously treated patients). At Month 12, 83.9% of patients were receiving the maximum dose of pitolisant, which was 36 mg/day. They found that pitolisant at once-daily doses of up to 36 mg were associated with a significant decrease in mean excessive daytime sleepiness score at the first on-treatment assessment (Month 1). The results persisted through 12 months of treatment. The investigators defined a clinically significant improvement in Epworth Sleepiness Scale (ESS) as a decrease of ≥ 3 points and they observed this clinically significant improvement at Month 12 when pitolisant was used as a monotherapy or in combination with other narcolepsy medications.
The investigators noted that approximately one-third of patients were taking ≥ 1 concomitant medication at study baseline: 12.7% methylphenidate, 9.8% modafinil, 8.8% venlafaxine, 6.9% sodium oxybate, 2.9% mazindol, and 2.0% selective serotonin reuptake inhibitors. This number increased to approximately one-half of patients taking ≥ 1 concomitant narcolepsy medication during the study: 22.5% methylphenidate, 17.6% modafinil, 13.7% venlafaxine, 10.8% sodium oxybate, 8.8% selective serotonin reuptake inhibitors, 3.9% mazindol, and 1% clomipramine.
Approximately half of the patients completed sleep diaries through Month 12 and these patients reported that the mean daily number of involuntary sleep attacks decreased by 27% (from 1.36 to 0.99). Patients also reported that treatment with pitolisant reduced the frequency of cataplexy and other symptoms of narcolepsy such as hypnagogic hallucinations and sleep paralysis. In particular, the investigators documented a 65-75% reduction in frequency of cataplexy attacks. This reduction of cataplexy was sustained through twelve months of open-label study.
In the second poster, Michael J. Thorpy, MB, ChB, Director of the Sleep-Wake Disorders Center at the Montefiore Medical Center, Bronx, New York and colleagues described the results of their naturalistic, open-label study of patients with narcolepsy. The improvements in excessive daytime sleepiness (EDS) and cataplexy were consistent with results from previous short-term, double-blind studies. Specifically, the improvements in narcolepsy symptoms were observed during the first month of treatment and sustained through Month 12. The investigators did not identify any additional safety concerns and thus described a safety profile that was consistent with that observed in previous short-term studies.