The FDA approved in adults with narcolepsy, drugmaker Harmony Biosciences said.
Pitolisant is the first treatment approved for patients with narcolepsy not scheduled as a controlled substance by the DEA, and "offers an important benefit/risk profile to address the unmet medical need that exists in people living with narcolepsy," Jeffrey Dayno, MD, Harmony's chief medical officer, said in a statement.
A first-in-class medication, pitolisant is a selective histamine 3 (H₃) receptor antagonist/inverse agonist that increases the synthesis and release of histamine to improve wakefulness; its exact mechanism of action is unclear. Patients take the drug orally once daily in the morning.
Pitolisant's efficacy was seen in two multicenter, randomized, double-blind, placebo-controlled studies of 261 narcolepsy patients, 75% to 80% of whom had a history of cataplexy. Treatment was for 8 weeks: a 3-week titration period followed by a 5-week stable dose phase. In both trials, pitolisant showed a statistically significant improvement in excessive daytime sleepiness on the Epworth Sleepiness Scale score, according to Harmony.
The most common adverse reactions associated with pitolisant -- occurring in 5% or more of trial participants and at twice the rate of placebo -- were insomnia (6%), nausea (6%), and anxiety (5%). Other side effects included headache, upper respiratory infection, musculoskeletal pain, increased heart rate, and decreased appetite.
Pitolisant is in patients with severe hepatic impairment. The drug has an effect on QT interval; the risk of QT prolongation may be greater in patients with liver or kidney disease. It is not recommended for patients with end-stage kidney disease.
Pitolisant has been approved in Europe since 2016. Harmony plans to make it the drug commercially available in the U.S. in the fourth quarter of 2019.