This supplemental approval makes pitolisant the only non-scheduled therapy approved in the US for both pediatric and adult patients with narcolepsy with or without cataplexy.

“With this approval, clinicians now have the option to prescribe WAKIX to treat excessive daytime sleepiness, cataplexy, or both, in patients 6 years and older with narcolepsy,” noted Kumar Budur, MD, MS, Chief Medical and Scientific Officer of Harmony Biosciences.

Pitolisant was approved in August 2019 for excessive daytime sleepiness in adult patients with narcolepsy, and the indication was expanded in October 2020 to include cataplexy in adults. In June 2024, the agency approved pitolisant for excessive daytime sleepiness in pediatric patients aged 6 years and older. The current approval extends the pediatric indication to include cataplexy.

Pitolisant is a selective histamine 3 receptor antagonist and inverse agonist. Although the precise mechanism of action is not fully established, its efficacy is believed to be mediated through histamine 3 receptor activity, leading to increased synthesis and release of histamine, a wake-promoting neurotransmitter. The drug received orphan drug designation for narcolepsy in 2010 and breakthrough therapy designation for cataplexy in 2018.

Narcolepsy is a rare, chronic neurologic disorder characterized by sleep-wake instability. It affects approximately 170,000 people in the US and is defined by excessive daytime sleepiness and cataplexy, along with other manifestations of rapid eye movement sleep dysregulation, including hallucinations and sleep paralysis. In most patients, narcolepsy is associated with loss of hypocretin or orexin signaling in the brain.

Pitolisant is contraindicated in patients with known hypersensitivity to the drug or with severe hepatic impairment. The medication prolongs the QT interval and should be avoided in patients with known QT prolongation, a history of cardiac arrhythmias, or other risk factors for torsade de pointes. In placebo-controlled trials in patients with narcolepsy with or without cataplexy, the most common adverse reactions in adults were insomnia, nausea, and anxiety. In pediatric trials, headache and insomnia were most frequently reported.

Source: Harmony Biosciences