FDA grants Priority Review to pitolisant for pediatric narcolepsy patients

The FDA has granted Priority Review designation to a supplemental New Drug Application (sNDA) for pitolisant (WAKIX; Harmony Biosciences) tablets for the treatment of excessive daytime sleepiness (EDS) or cataplexy in patients aged 6 years and older with narcolepsy.¹

According to Harmony Biosciences, the federal agency has assigned a Prescription Drug User Fee Act (PDUFA) target action date of June 21, 2024.¹

The rare and chronic neurological disease affects approximately 170,000 Americans and is commonly characterized by EDS and cataplexy in addition to other manifestations of REM sleep dysregulation. EDS is present in all people with narcolepsy, Harmony stated, which results in the inability to stay awake and alert during the day.¹

The disease that affects men and women equally is caused in most patients by the loss of hypocretin/orexin, a neuropeptide in the brain that supports sleep-wake stability. Typical symptom onset occurs in adolescence or young adulthood, though proper diagnosis could take up to 10 years, according to Harmony.¹

Priority Review designation and the acceptance of the sNDA was based on a phase 3, multicenter, randomized, and placebo-controlled study evaluating the safety and efficacy of pitolisant in patients aged 6 to younger than 18 years with narcolepsy, with or without cataplexy (NCT02611687).¹

The study was published in The Lancet Neurology and featured 110 patients with cataplexy (mean age 12.9 years [SD 3.0 years]) from 11 total sleep centers across 5 countries including France, Italy, Netherlands, Finland, and Russia.²

According to the study, "participants were required to have a Pediatric Daytime Sleepiness Scale score of 15 or greater and to have not received psychostimulants for at least 14 days before [enrollment]; participants who needed anticataplectics (including sodium oxybate) were required to have been on a stable dose for at least 1 month."²

At a 2:1 ratio, patients were randomly assigned to treatment with pitolisant or placebo. Patients entered a 4-week individual up-trition scheme from 5 mg per day to a maximum of 40 mg per day of pitolisant or placebo. This followed a 4-week screening period that included a 2-week baseline period.²

"For the primary analysis, we assessed 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 [1] dose of treatment and who had at least [1] baseline UNS value," wrote the study investigators.²

The decrease in the UNS total score reflected a reduction in EDS and cataplexy.²

In the study period from June 6, 2016, to April 3, 2021, 72 patients were assigned to pitolisant and 38 to placebo. A total of 107 patients completed the double-blind period.²

In the pitolisant group, the mean adjusted difference in the UNS total score from baseline to the end of the double-blind period was –6.3 (SE 1.1). In the placebo group the difference was –2.6 (1.4) (least squares mean difference –3.7; 95% CI –6.4 to –1.0, [P = 0.007]).²

According to results, treatment-emergent adverse events were recorded in 22 of 72 pitolisant-group patients and 13 of 38 patients in the placebo group.²

The most frequent adverse events reported (≥5% of patients) in either group were headache (14 pitolisant group, 3 placebo group) and insomnia (5 pitolisant group, 1 placebo group).²

Pitolisant, a selective histamine 3 (H₃) receptor antagonist/inverse agonist, is approved by the FDA to treat EDS or cataplexy in adult patients with narcolepsy, commercially available in the United States since 2019.¹

References:

1. US Food and Drug Administration grants Priority Review to Harmony Biosciences' application for WAKIX (pitolisant) in pediatric narcolepsy. Harmony Biosciences. Press release. February 21, 2024. Accessed February 22, 2024. https://ir.harmonybiosciences.com/news-releases/news-release-details/us-food-and-drug-administration-grants-priority-review-harmony

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 [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