FDA Approves pitolisant-first non-controlled substance treatment for Narcolepsy

The US Food and Drug Administration (FDA) approved WAKIX (pitolisant) as the first treatment for patients with narcolepsy that is not scheduled as a controlled substance by the US Drug Enforcement Administration (DEA).WAKIX was first granted orphan drug status by the Food and Drug Administration to treat narcolepsy in 2010.

The once-daily drug for excessive daytime sleepiness (EDS) in adult patients with narcolepsy is developed by Harmony Biosciences and may hit the market by the end of the year.It is also the first treatment for narcolepsy approved by the Food and Drug Administration that is not considered a controlled substance by the U.S. Drug Enforcement Agency. The Food and Drug Administration acted quickly in approving Wakix under Priority Review after accepting Harmony’s New Drug Application in February.

Wakix (pitolisant), a first-in-class medication, is a selective histamine 3 (H₃) receptor antagonist/inverse agonist that works through a novel mechanism of action to increase the synthesis and release of histamine, a wake-promoting neurotransmitter in the brain. Patients take the oral treatment in the morning after they wake up, the company noted.

Narcolepsy is a sleep disorder characterized by excessive sleepiness, sleep paralysis and hallucinations. The disorder can also cause partial or total loss of muscle control, a condition known as cataplexy. In most patients, narcolepsy is caused by the loss of hypocretin, a neuropeptide in the brain that supports sleep-wake state stability. Narcolepsy affects about 200,000 people in the U.S., Harmony said.

The efficacy of WAKIX for the treatment of EDS in adult patients with narcolepsy was evaluated in 2 multicenter, randomized, double-blind, placebo-controlled studies that included 261 patients that received the drug, placebo, or active control.

Treatment duration was 8 weeks, with a 3-week dose-titration phase followed by a 5-week stable dose phase.

In both of these studies, WAKIX demonstrated a statistically significant improvement in EDS. 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 WAKIX were insomnia (6%), nausea (6%), and anxiety (5%).

"We are extremely proud to bring WAKIX to market for those living with narcolepsy, a chronic, debilitating, rare neurologic disorder," Harmony's Chairman and Chief Executive Officer, John C. Jacobs, said in a statement. "At Harmony, we share a vision to develop novel treatment options for people living with rare diseases, with a focus on those that affect the central nervous system. The approval of WAKIX strengthens our commitment to making that vision a reality."

"The approval of WAKIX provides healthcare professionals managing people living with narcolepsy a new and important treatment option for their patients," Harmony's Chief Medical Officer, Jeffrey Dayno, MD, said in a statement. "Additionally, WAKIX 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."