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The analyses focus on the abuse potential, efficacy in high-burden patients with narcolepsy, and safety data for Harmony Biosciences’ histamine H3 receptor-antagonist/inverse agonist, pitolisant.
Jeffrey Dayno, MD
At the World Sleep 2019 meeting in Vancouver, Canada, Harmony Biosciences will present data for its recently FDA-approved agent, pitolisant (Wakix), in an oral presentation and a number of posters. Altogether, the data highlight abuse potential, efficacy in high-burden patients with narcolepsy, and safety data.1
The oral presentation, to be delivered on September 25 (Session Oral 28), will offer the results of a randomized, double-blind, active- and placebo-controlled, 4-sequence 4-way crossover study of a single-dose of pitolisant compared with the stimulant phentermine HCl and placebo in those who are nondependent, recreational stimulant users.
"Harmony looks forward to sharing clinical data for Wakix at the World Sleep 2019 meeting, which will shed light on its product profile as the first and only approved treatment for patients with narcolepsy that is not scheduled as a controlled substance," said Jeffrey Dayno, MD, chief medical officer, Harmony Biosciences. "These data reflect the breadth of scientific evidence in support of Wakix, and further demonstrate its uniqueness as a first-in-class molecule with a novel mechanism of action. We look forward to presenting these data to a global audience."
In August, Dayno told NeurologyLive that the recommended dose range for the therapy, which will be commercially available to healthcare professionals and appropriate patients in the fourth quarter of this year, is 17.8 mg to 35.6 mg administered orally once daily in the morning upon wakening. The treatment has been available through an expanded access program called Pitolisant Expanded Access Clinical Evaluation, or PEACE, to those with excessive daytime sleepiness associated with narcolepsy in addition to cataplexy associated with narcolepsy.
Additionally, 7 scientific posters will be presented at the meeting, consisting of a new post hoc analysis of pooled data from 2 studies of pitolisant in adults with narcolepsy with a high burden of narcolepsy symptoms, set to be presented on September 24 (Session P3). Data from the Harmony 3 study, focused on the 1-year analysis of long-term safety and efficacy, are expected to be presented in a session on September 23 (Session P2).
Pitolisant, the first of the histamine H3 receptor-antagonist/inverse agonist class, which works by enhancing the histaminergic neurons in the brain, was approved for the treatment of excessive daytime sleepiness in patients with narcolepsy in August 2019. Its new drug application was backed by data from the clinical development program which included more than 300 patients, as well as safety data on more than 1500 patients across multiple patient populations.
In the HARMONY 1 and HARMONY 1bis trials, the treatment showed statistically significant improvements in excessive daytime sleepiness over a 3-week titration period and a 5-week stable dose phase. Data presented in 2018 showed that the drug led to long-term improvements in excessive daytime sleepiness, as measured by the Epworth Sleepiness Scale (ESS). Patients in the study had ESS scores of 16.8 at baseline, which were reduced to 13.4 after 1 year, and to 10.6—levels which are considered normal—by year 5.2
Additionally, the therapy showed that multiple symptoms of REM dysregulation were reduced from baseline to year 1. Symptoms of cataplexy were reduced by 76%, hypnagogic hallucinations were reduced by 54%, and sleep paralysis was reduced by 62%. The most common adverse events (AEs) occurring in ≥5% of patients taking pitolisant were insomnia (6%), nausea (6%), and anxiety (5%).
In June, Harmony presented pooled safety data from 4 placebo-controlled trials totaling more than 300 patients at SLEEP 2019. It was considered both generally safe and well-tolerated, with an overall incidence of AEs in the dataset of 49.4%, compared to 41.2% with placebo.3
The small-molecule inhibitor was also granted breakthrough therapy and fast track designation in 2017 as a potential treatment for cataplexy in those with narcolepsy, in which it has shown some success. In a 106-patient, phase 3 study, pitolisant was shown to reduce the weekly cataplexy rate by 75% from baseline compared with a decrease of 38% with placebo (rate ratio, 0.512; 95% CI, 0.43-0.60; P <.0001). In a post-hoc analysis, this benefit remained consistent across all patient subgroups.4
1. Harmony Biosciences To Present Clinical Data On WAKIX® (pitolisant) At Upcoming World Sleep 2019 [press release]. Plymouth Meeting, PA: Harmony; Published September 16, 2019. prnewswire.com/news-releases/harmony-biosciences-to-present-clinical-data-on-wakix-pitolisant-at-upcoming-world-sleep-2019-300918558.html. Accessed September 19, 2019.
2. Harmony Biosciences presents 5-year data on pitolisant at international narcolepsy symposium [news release]. Plymouth Meeting, PA: Harmony Biosciences; September 11, 2018. harmonybiosci­ences.com/newsroom/harmony-biosciences-presents-5-year-data-on-pitolisant-at-international. Accessed August 15, 2019.
3. Scart-Grès C, Momah C, Roy M, Maski K, Piris S, Bogan RK. Sleep. 2019;42(Suppl 1):A244—A245. doi: 10.1093/sleep/zsz067.612. Presented at: SLEEP 2019. June 8-12, 2019; San Antonio, TX. Abstract 0614.
4. Szakacs Z, Dauvilliers Y, Mikhaylov V, et al. Safety and efficacy of pitolisant on cataplexy in patients with narcolepsy: a randomised, double-blind, placebo-controlled trial. Lancet Neuro. 2017;16(3):200-207.