Pitolisant for Treatment of Patients with Narcolepsy has Long-Term Safety, Tolerability, and Durability of Effect


Long-term data for pitolisant (Harmony Biosciences, Plymouth Meeting PA), an investigational treatment for excessive daytime sleepiness (EDS) and cataplexy in patients with narcolepsy, were presented at the 7th International Symposium on Narcolepsy in Beverly, MA. 

Patients had improvements in EDS measured with the Epworth Sleepiness Scale (ESS); baseline ESS was 16.8, 13.4 after 1 year of treatment, and 10.6 at the end of the 5-year study. Over the first year, REM dysregulation symptoms were also reduced: cataplexy (-76%), hypnagogic hallucinations (-54%) and sleep paralysis (-62%). There was limited data from patient diaries at year 5 to assess these symptoms.

The safety and tolerability profile of pitolisant was consistent with that reported previously; common adverse events were headache, insomnia, weight gain, anxiety, depression, nausea, vomiting, and irritability; 16% of patients discontinued treatment due to adverse events. No evidence of tolerability or withdrawal symptoms was seen when patients stopped using pitolisant. 

“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, MD

This study used an open-label long-term naturalistic study design; 77 patients who had participated in the Harmony III trial (NCT01399606) were invited to participate in an extension period assessing results every 6 months over a 5-year period. A total of 50 (65%) patients completed a first year of treatment; 48 participated in the extension, with 32 patients remaining on pitolisant for 5 years or until the study ended. The maintenance dose of 40 mg once daily was used by 80-88% of patients throughout the study. 

Pitolisant is an investigational high-potency and highly selective histamine 3 (H3) receptor antagonist/inverse agonist thought to inhibit cataplexy through activation of the histaminergic system. If approved, pitolisant will be the first new therapy for EDS and cataplexy in the US in more than 10 years.

The Food and Drug Administration (FDA) has granted pitolisant 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. These designations accelerate the standard drug-review process for treatments that may benefit people with unmet medical needs.  


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