FDA Approves Pitolisant for Excessive Daytime Sleepiness in Pediatric Patients


FDA approves pitolisant for excessive daytime sleepiness and cataplexy in pediatric patients aged ≥ 6 years with narcolepsy.

FDA Approves Pitolisant for Excessive Daytime Sleepiness in Pediatric Patients

Credit: US Food and Drug Administration

The US Food and Drug Administration (FDA) has approved the supplemental New Drug Application for pitolisant (Wakix) tablets to treat excessive daytime sleepiness in pediatric patients aged ≥6 years with narcolepsy.1

"Following the FDA's decision to grant priority review, we are very pleased with the Agency's timely review and approval of WAKIX for pediatric narcolepsy patients with excessive daytime sleepiness," Jeffrey M. Dayno, MD, president and chief executive officer of Harmony Biosciences, said in a statement. "EDS is the primary symptom experienced by all patients with narcolepsy and this approval for WAKIX, as the first-and-only FDA-approved non-scheduled treatment option for narcolepsy, makes this important treatment option available to pediatric patients 6 years and older living with narcolepsy."

Pitolisant, a selective histamine 3 (H3) receptor antagonist/inverse agonist, has already been commercially available for this indication in adults since the last quarter of 2019.2 Now it is approved for children and adolescents, too.

This first-in-class medication works by increasing the synthesis and releasing histamine to promote wakefulness in the brain. Harmony Biosciences said pitolisant was the only approved treatment for narcolepsy that was not scheduled as a controlled substance by the US Drug and Enforcement Agency.

Approved 4 months after Harmony Biosciences announced the FDA had granted a priority review designation to their application, the approval was based on a 5-week phase 3 multicenter, randomized (2:1), placebo-controlled study, led by Yves Dauvilliers, MD, from the Guide-Chauliac Hospital, University of Montpellier in France.3

Conducted by Bioprojet in France, who gave Harmony Biosciences an exclusive license to develop, manufacture, and market pitolisant in the United States, the pivotal trial evaluated the safety and efficacy of pitolisant in 110 pediatric patients aged 6 – 17 years with narcolepsy who either have or do not have cataplexy. Investigators saw the mean adjusted difference in the Ullanlinna Narcolepsy Scale total score from baseline to the end of the double-blind period was -6.3 in the pitolisant group and -2.6 in the placebo group (95% CI, -6.4 to -1.0; P = .007).4

Placebo-controlled clinical trials showed common adverse events included insomnia (6%), nausea (6%), and anxiety (5%). Less common adverse events, but still more common in patients on pitolisant versus placebo, included headache, upper respiratory tract infection, musculoskeletal pain, increased heart rate, hallucinations, irritability, abdominal pain, sleep disturbance, decreased appetite, cataplexy, dry mouth, and rash.

Harmony Biosciences has just begun a phase 3 study evaluating pitolisant for excessive daytime sleepiness in patients with Prader-Willi Syndrome, aged ≥6 years, with participant enrollment starting in April 2024.5

“This could be life-altering for these patients,” investigator Amee Revana, DO, from Baylor College of Medicine and Texas Children's Hospital, told HCPLive at SLEEP 2024, the 38th annual meeting of the Associated Professional Sleep Societies.

Kumar Budur, MD, MS, chief medical and scientific officer of Harmony Biosciences, added in the press release that the company plans to discuss with the FDA "a path forward for a cataplexy indication in pediatric narcolepsy patients" as well.1

"We appreciate the FDA's recognition of the unmet medical need in this patient population and their approval of the EDS indication, making WAKIX available to every appropriate pediatric patient 6 years and older living with narcolepsy," Budur said.


  1. Harmony Biosciences. HARMONY BIOSCIENCES RECEIVES U.S. FOOD AND DRUG ADMINISTRATION APPROVAL FOR WAKIX® (PITOLISANT) IN PEDIATRIC PATIENTS WITH NARCOLEPSY. Press release. Published June 24, 2024. https://ir.harmonybiosciences.com/news-releases/news-release-details/harmony-biosciences-receives-us-food-and-drug-administration-0
  2. FDA Approves Wakix for The Treatment of Narcolepsy. AASM. February 17, 2020. https://aasm.org/fda-approves-wakix-for-the-treatment-of-narcolepsy/. Accessed June 18, 2024.
  3. 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 [published correction appears in Lancet Neurol. 2023 May;22(5):e7. doi: 10.1016/S1474-4422(23)00119-9] [published correction appears in Lancet Neurol. 2023 Oct;22(10):e11. doi: 10.1016/S1474-4422(23)00333-2]. Lancet Neurol. 2023;22(4):303-311. doi:10.1016/S1474-4422(23)00036-4
  4. U.S. Food and Drug Administration Grants Priority Review to Harmony Biosciences' Application for Wakix® (Pitolisant) In Pediatric Narcolepsy. PR Newswire. February 21, 2024. https://www.prnewswire.com/news-releases/us-food-and-drug-administration-grants-priority-review-to-harmony-biosciences-application-for-wakix-pitolisant-in-pediatric-narcolepsy-302066778.html. Accessed June 18, 2024.
  5. Derman, C. Amee Revana, DO, FAASM: Pitolisant Reduces Sleepiness in Prader-Willi Syndrome. HCPLive. June 3, 2024. https://www.hcplive.com/view/amee-revana-do-faasm-pitolisant-reduces-sleepiness-in-prader-willi-syndrome. Accessed June 18, 2024.
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