FDA Approves Pitolisant for Daytime Sleepiness in Patients with Narcolepsy

The US Food and Drug Administration has approved pitolisant (Wakix, Harmony Biosciences) for the treatment of excessive daytime sleepiness (EDS) in adult patients with narcolepsy. Pitolisant is the first and only treatment approved for patients with narcolepsy that is not scheduled as a controlled substance by the US Drug Enforcement Administration.

Pitolisant, a first-in-class medication, is a selective histamine 3 (H₃) receptor antagonist/inverse agonist that increases the synthesis and release of histamine, a wake-promoting neurotransmitter in the brain. Pitolisant is administered orally once daily in the morning when a patient wakes up.

"The approval of Pitolisant provides health care professionals managing people living with narcolepsy a new and important treatment option for their patients," said Jeffrey Dayno, MD, chief medical officer of Harmony. "Additionally, pitolisant is the only non-scheduled treatment option approved for adult patients with narcolepsy, and it offers an important benefit/risk profile to address the unmet medical need that exists in people living with narcolepsy."

The efficacy of pitolisant for the treatment of EDS in adult patients with narcolepsy was evaluated in 2 multicenter, randomized, double-blind, placebo-controlled studies (HARMONY 1 and HARMONY 1bis). These studies included a total of 261 patients who were randomized to receive pitolisant, placebo, or active control; these patients had a median age of 37 (HARMONY 1) and 40 (HARMONY 1bis).

Treatment duration was 8 weeks, with a 3-week dose titration phase followed by a 5-week stable dose phase; 75% to 80% of the patients in these studies had a history of cataplexy. In both of these studies, pitolisant demonstrated a statistically significant improvement in EDS as measured by the Epworth Sleepiness Scale (ESS) score. In the placebo-controlled trials conducted in patients with narcolepsy with or without cataplexy, the most common adverse reactions (occurring in ≥5% of patients and at twice the rate of placebo) with the use of pitolisant were insomnia (6%), nausea (6%), and anxiety (5%).

Pitolisant is expected to be commercially available to healthcare professionals and appropriate patients in the US in the fourth quarter of 2019.