FDA approves pitolisant for narcolepsy patients aged 6 years and older

FDA approves pitolisant for narcolepsy patients aged 6 years and older | Image Credit: © Calin - © Calin - stock.adobe.com.

The FDA has approved Harmony Biosciences' pitolisant tablets (WAKIX) to treat excessive daytime sleepiness (EDS) in patients aged 6 years and older with narcolepsy.^1,2

A FDA-separated submission for the treatment of cataplexy in pediatric patients aged 6 to less than 18 years of age was issued a complete response, according to a press release from Harmony Biosciences.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," said Jeffrey M. Dayno, MD, president and chief executive officer of Harmony Biosciences 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."¹

The decision makes pitolisant the first and only FDA-approved, non-scheduled treatment option for daytime sleepiness in this patient population.¹

Regarding the cataplexy indication, Kumar Budur, MD, MS, chief medical and scientific officer at Harmony Biosciences said ongoing talks with the FDA will occur.¹

"We plan to discuss with the Agency a path forward for a cataplexy indication in pediatric narcolepsy patients based on the strength of the existing data from Bioprojet's Phase 3 trial," said Budur. "We appreciate the FDA's recognition of the unmet medical need in this patient population and their approval of the EDS indication, making [pitolisant] available to every appropriate pediatric patient 6 years and older living with narcolepsy."¹

The acceptance of the supplemental New Drug Application (sNDA) with Priority Review on February 21, 2024, was based on a phase 3 randomized, multicenter, placebo-controlled study (NCT02611687) that evaluated safety and efficacy in pediatric patients aged 6 years to <18 years.^2,3

According to The Lancet Neurology, study participants were required to have a Pediatric Daytime Sleepiness Scale score of 15 or greater. Individuals were not to have received psychostimulants for at least 14 days before study enrollment. Participants were assigned randomly to pitolisant or placebo at a 2:1 ratio.³

Following a 4-week screening period, patients entered a 4-week individual up-titration scheme, from 5 mg per day to a maximum of 40 mg per day or pitolisant or placebo, wrote the study authors. The primary analysis was "pitolisant versus placebo using change in the Ullanlinna Narcolepsy Scale (UNS) total score from baseline to the end of double-blind period in the full analysis set, defined as all randomly allocated patients who received at least one dose of treatment and who had at least one baseline UNS value," stated the investigators.³

A decrease in the UNS total represents a reduction in both EDS and cataplexy. There were 115 were screened, with 110 randomly assigned (72 pitolisant, 38 placebo) (mean age 12·9 [SD 3·0] years, 61 [55%] male, and 90 [82%] with cataplexy).³

In the pitolisant group, the mean adjusted difference in UNS total score from baseline to the end of double-blinding was –6.3, while in the placebo group the mean adjusted difference was –2.6 (least squares mean difference -3·7; 95% CI -6·4 to -1·0, [P = 0·007]).³

According to The Lancet, treatment-emergent adverse events were reported in 31% in the pitolisant group and 34% of placebo patients.

The investigators concluded "Pitolisant treatment resulted in an improvement in narcolepsy symptoms in children, although the UNS was not validated for use in children with narcolepsy when our study began."

References:

1. Harmony Biosciences receives US Food and Drug Administration approval for WAKIX® (pitolisant) in pediatric patients with narcolepsy. Harmony Biosciences. Press release. June 24, 2024. Accessed June 24, 2024. https://ir.harmonybiosciences.com/news-releases/news-release-details/harmony-biosciences-receives-us-food-and-drug-administration-0

2. US Food and Drug Administration grants Priority Review to Harmony Biosciences' application for WAKIX (pitolisant) in pediatric narcolepsy. February 21, 2024. Accessed April 26, 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

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 Mar 24;:] [published correction appears in Lancet Neurol. 2023 Oct;22(10):e11]. Lancet Neurol. 2023;22(4):303-311. doi:10.1016/S1474-4422(23)00036-4