FDA approves pitolisant (Wakix) for cataplexy in pediatric narcolepsy

The FDA has approved a supplemental new drug application for Wakix (pitolisant) tablets for the treatment of cataplexy in pediatric patients 6 years and older with narcolepsy. According to Harmony Biosciences, the approval makes pitolisant the first and only FDA-approved, nonscheduled treatment for pediatric and adult patients with narcolepsy with or without cataplexy.¹

“We are excited to achieve this important milestone for pediatric narcolepsy patients who experience cataplexy,” said Kumar Budur, MD, MS, chief medical and scientific officer of Harmony Biosciences. “With this approval, clinicians now have the option to prescribe Wakix to treat excessive daytime sleepiness [EDS], cataplexy, or both, in patients 6 years and older with narcolepsy.”

The pediatric approval is supported in part by a phase 3, double-blind, randomized, placebo-controlled, multisite study evaluating pitolisant in children aged 6 to 17 years with narcolepsy with or without cataplexy (NCT02611687).² The study enrolled patients at 11 sleep centers across 5 countries. Participants were randomly assigned 2:1 to pitolisant or placebo following a screening and baseline period, with dose titration from 5 mg daily to a maximum of 40 mg daily over 4 weeks, followed by 4 weeks at a stable dose.

The primary end point was the change from baseline to the end of the double-blind period in the Ullanlinna Narcolepsy Scale (UNS) total score in the full analysis set. A decrease in the UNS total score reflects a reduction in both EDS and cataplexy. Among 110 randomly assigned participants (mean age, 12.9 years; 55% male; 82% with cataplexy), 107 completed the double-blind period. The mean adjusted difference in UNS total score from baseline to the end of the double-blind period was −6.3 (SE, 1.1) in the pitolisant group, and −2.6 (1.4) in the placebo group, corresponding to a least squares mean difference of −3.7 (95% CI, −6.4 to −1.0; P = .007).

Treatment-emergent adverse events were reported in 31% of patients receiving pitolisant and 34% of those receiving placebo. The most frequently reported adverse events affecting at least 5% of patients in either group were headache (19% with pitolisant vs 8% with placebo) and insomnia (7% vs 3%). Investigators reported that the safety profile in children was similar to that observed in adults, although the UNS was not validated for pediatric use at the time the study began and further data are needed to confirm long-term safety.

Pitolisant was first approved in August 2019 for the treatment of EDS in adults with narcolepsy, with the indication expanded in October 2020 to include cataplexy in adults. In June 2024, the FDA approved pitolisant for the treatment of EDS in pediatric patients6 years and older with narcolepsy.

“Wakix is now the first-and-only FDA-approved treatment option for both pediatric and adult narcolepsy patients with or without cataplexy that is not scheduled as a controlled substance, an important distinction that supports its clinical utility,” said Jeffrey M. Dayno, MD, president and CEO of Harmony Biosciences.

Pitolisant is a selective histamine 3 (H₃) receptor antagonist/inverse agonist. Although its mechanism of action is not fully understood, its efficacy may be mediated through activity at H₃ receptors, leading to increased synthesis and release of histamine, a neurotransmitter involved in wake promotion.

According to the prescribing information, pitolisant is indicated for the treatment of EDS or cataplexy in patients 6 years and older with narcolepsy. It is contraindicated in patients with known hypersensitivity to pitolisant or any component of the formulation and in patients with severe hepatic impairment.

Pitolisant prolongs the QT interval and should be avoided in patients with known QT prolongation or in combination with other QT-prolonging agents. Dosage adjustments are recommended in patients with moderate hepatic impairment or moderate to severe renal impairment, and the drug is not recommended in end-stage renal disease.

References

1. Harmony Biosciences receives U.S. Food and Drug Administration approval for Wakix (pitolisant) for the treatment of cataplexy in pediatric narcolepsy. News release. Harmony Biosciences. February 17, 2026. Accessed February 17, 2026. https://ir.harmonybiosciences.com/news-releases/news-release-details/harmony-biosciences-receives-us-food-and-drug-administration-1
2. Dauvilliers Y, Lecendreux M, Lammers GJ, et al. Safety and efficacy of pitolisant in children aged 6 years or older with narcolepsy with or without cataplexy: a double-blind, randomised, placebo-controlled trial. Lancet Neurol. 2023;22(4):303-311. doi:10.1016/S1474-4422(23)00036-4