Promising Data for First New Narcolepsy Drug in Ten Years, Pending Approval

Platform presentation highlights open-label, long-term safety and tolerability results, durability of effect over time in both EDS and cataplexy in patients with narcolepsy Harmony Biosciences, LLC (Harmony) recently presented new data on pitolisant at the 7th International Symposium on Narcolepsy in Beverly, MA. Pitolisant is an investigational product that has been studied for the treatment of both excessive daytime sleepiness (EDS) and cataplexy in adult patients with narcolepsy. Long-term data (up to 5-years) from the Harmony III open-label, naturalistic study were presented in a platform presentation. These data assessed the safety, tolerability and durability of effect of pitolisant, the first potent and highly selective histamine 3 (H3) receptor antagonist/inverse agonist. If approved, pitolisant would represent the first new therapy in the U.S. in over a decade for the treatment of both EDS and cataplexy in patients with narcolepsy. “The Harmony III open-label, long-term study for pitolisant reflects real-world experience of people living with the debilitating effects of excessive daytime sleepiness and cataplexy in narcolepsy,” said Harmony’s Chief Medical Officer, Jeffrey Dayno, M.D. “Pitolisant is a first-in-class molecule with a novel mechanism of action that works through the histaminergic system to improve wakefulness and inhibit attacks of cataplexy. In an extension of the Harmony III long-term study, the safety, tolerability, and durability of effect of pitolisant were assessed out to five years in those patients who stayed in the study until the end.” Patients (n=77) from the French sites in the Harmony III trial were invited to participate in the extension period up to 5 years with follow-up visits every 6 months. Among this cohort, 50 patients (65%) completed the first 12 month period, 48 elected to participate in the extension period, and 32 of those (67%) stayed on pitolisant treatment for 5 years or until the study ended. Eighty to 88% of patients were maintained on pitolisant 40 mg once daily during the study. Summary findings for the study concluded:  Maintenance of effect for pitolisant in improving EDS was demonstrated using the Epworth Sleepiness Scale (ESS); baseline ESS was 16.8, decreased to 13.4 at year 1, then continued to improve over the course of the study with an ESS of 10.6 at year 5  Symptoms of REM dysregulation were reduced from baseline to year 1 as follows: cataplexy (-76%), hypnagogic hallucinations (-54%) and sleep paralysis (-62%); limited data from patient diaries were available at year 5 to assess these symptoms  The safety and tolerability profile of pitolisant was demonstrated to be consistent with that reported in the randomized controlled trials for pitolisant; common adverse events were headache, insomnia, weight increase, anxiety, depression, nausea, vomiting and irritability; 16% of patients discontinued treatment due to adverse events  There was no evidence of the development of tolerance with long-term use of pitolisant and there were no reports of symptoms related to withdrawal when patients discontinued treatment with pitolisant About Pitolisant Pitolisant is an investigational medication in the U.S. that is not approved by the FDA. It was granted orphan designation for the treatment of narcolepsy, Fast Track designation for the treatment of excessive daytime sleepiness (EDS) and cataplexy in patients with narcolepsy, and Breakthrough Therapy designation for the treatment of cataplexy in patients with narcolepsy. Pitolisant is the first potent and highly selective histamine 3 (H 3 ) receptor antagonist/inverse agonist; it enhances the activity of histaminergic neurons in the brain that function to improve a patient’s wakefulness and inhibit attacks of cataplexy. It was developed by Bioprojet who has marketed the product in Europe since its approval by the European Medicines Agency in 2016. The receipt of Breakthrough Therapy and Fast Track designations for pitolisant afforded Harmony the opportunity to request a rolling NDA submission to the FDA, which was granted. Harmony’s goal is to obtain FDA approval to market this new medication in the U.S. in 2019. If approved, pitolisant would represent the first new therapy in the U.S. in over a decade for the treatment of both excessive daytime sleepiness (EDS) and cataplexy in patients with narcolepsy.

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