FDA Approves Pitolisant for Cataplexy in Narcolepsy


The drug, marketed as Wakix, was previously approved for the treatment of excessive daytime sleepiness in adults with narcolepsy.

Jeffrey Dayno, MD, Harmony Biosciences

Jeffrey Dayno, MD

Harmony Biosciences has announced that the FDA has expanded the indication for pitolisant (Wakix) for the treatment of cataplexy in adults with narcolepsy. Notably, pitolisant is the only FDA-approved treatment for both excessive daytime sleepiness and cataplexy in narcolepsy that is not a scheduled controlled substance.1

Pitolisant is a novel, selective histamine 3 receptor antagonist/inverse agonist that increases the synthesis and release of wake-promoting histamine via a once-daily, oral administration.

"All people living with narcolepsy have excessive daytime sleepiness and up to two-thirds of them also experience cataplexy, which is one of the most debilitating symptoms of this chronic, rare neurological disorder," said Harmony's chief medical officer, Jeffrey Dayno, MD, in a statement.1 "Today's FDA approval of the cataplexy indication for Wakix, coupled with it being the first and only non-scheduled treatment option approved for adult patients with narcolepsy to treat both excessive daytime sleepiness or cataplexy, provides an opportunity for Wakix to offer broad clinical utility to healthcare professionals managing adult patients living with narcolepsy."

The expanded approval was based on results from the HARMONY CTP (NCT018000450) and HARMONY 1 (NCT01067222) randomized, controlled clinical trials, the results of which were reanalyzed after the FDA issued Harmony a complete response letter in August 2019 regarding data supporting the efficacy of pitolisant for the reduction of cataplexy.

Results from the CTP study demonstrated a 75% reduction in weekly cataplexy rate in patients taking pitolisant compared with 38% in patients in the placebo group (rate ratio 0.512; 95% CI, 0.43-0.60, P< .0001).2 Post-hoc analyses from the HARMONY 1 trial showed that pitolisant was superior to placebo but not non-inferior to modafinil for improvement in cataplexy rate from baseline.3

Additional long-term data showed a 76% reduction cataplexy from baseline to 1 year.4 Adverse events were consistent with what was observed throughout the clinical trial program, with the most common being headache, insomnia, weight increase, anxiety, depression, nausea, vomiting, and irritability.

The FDA originally approved pitolisant for the treatment of excessive daytime sleepiness in adults with narcolepsy in August 2019.5

1. Harmony Biosciences receives FDA approval for expanded use of Wakix (pitolisant) for the treatment of cataplexy in adult patients with narcolepsy. News release. Harmony Biosciences. October 14, 2020. Accessed October 14, 2020. https://www.prnewswire.com/news-releases/harmony-biosciences-receives-fda-approval-for-expanded-use-of-wakix-pitolisant-for-the-treatment-of-cataplexy-in-adult-patients-with-narcolepsy-301152078.html
2. Szakacs Z, Dauvilliers Y, Mikhaylov V, et al. Safety and efficacy of pitolisant on cataplexy in patients with narcolepsy: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2017(3):200-207. doi: 10.1016/S1474-4422(16)30333-7
3. Dauvilliers Y, Bassetti C, Lammers GJ, et al. Pitolisant versus placebo or modafinil in patients with narcolepsy: a double-blind, randomised trial. Lancet Neurol. 2013(11):1068-1075. doi: 10.1016/S1474-4422(13)70225-4
4. Harmony Biosciences presents 5-year data on pitolisant at International Narcolepsy Symposium. News releases. September 11, 2018. Accessed October 14, 2020. https://www.harmonybiosciences.com/newsroom/harmony-biosciences-presents-5-year-data-on-pitolisant-at-international/
5. WAKIX represents the first and only non-scheduled treatment approved for patients with narcolepsy in the U.S. News release. Harmony Biosciences. August 15, 2019. Accessed October 14, 2020. https://www.finance.yahoo.com/news/harmony-biosciences-announces-fda-approval-120000845.html
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