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Investigational narcolepsy drug safe, effective, with low abuse potential in several small trials

Data suggest that pitolisant, a histamine 3-receptor antagonist/inverse agonist under development for narcolepsy treatment, showed limited abuse potential and other benefits, according to findings presented at SLEEP.

A review in Nature of Science and Sleep indicated that medications currently available to treat either the excessive daytime sleepiness that plagues patients with narcolepsy; cataplexy alone; or excessive daytime sleepiness and cataplexy have abuse, adherence and tolerability concerns.

In the new study, Jeffrey M. Dayno, MD, executive vice president and chief medical officer, Harmony Biosciences, and colleagues randomly assigned 38 patients (mean age, 33.3 years; 73.7% male; 65.8% white) to receive either a therapeutic 35.6-mg dose of pitolisant (Harmony Biosciences), a supratherapeutic 213.6-mg dose of pitolisant, 60 mg of phentermine HCl or placebo.

 

Data suggest that pitolisant, a histamine 3-receptor antagonist/inverse agonist under development for narcolepsy treatment, showed limited abuse potential and other benefits, according to findings presented at SLEEP.

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Researchers found that both pitolisant doses yielded peak effect “overall drug liking,” “take drug again” and “drug liking at this moment” scores that were significantly lower vs. phentermine (P < .0001) and similar to placebo. The most common adverse event among patients receiving pitolisant was headache.

Other data on the drug’s impact in patients with narcolepsy released at SLEEP included:

• Catherine Scart-Grès, MD, of Bioprojet Pharma in Paris, and colleagues pooled data from four randomized, placebo-controlled trials up to 8 weeks in duration. This analysis consisted of 303 patients (mean age, 39.2 years; 54.5% men) who were “flexibly dosed” up to 35.6-mg of the drug daily and showed “pitolisant offered a favorable risk/benefit profile.”
• 14 patients (mean age, 34.3 years; 64.3%, women) treated with daily doses of either 17.8-mg, 26.7-mg or 35.6-mg of the drug for 6 to 12 months had similar total sleep time, sleep efficiency and arousal index scores after treatment as they did at baseline. “There was [also] generally no change” in Pittsburgh Sleep Quality Index scores except for the sleep efficient component, Ulf Kallweit and Annika Triller of the Universität Witten-Herdecke in Germany, wrote.
• Karl Doghramji, MD, of Thomas Jefferson University and colleagues’ open-label, crossover study looked at pharmacokinetic interactions of 16 men who received a single 35.6-mg dose of pitolisant with a divided 4.5-g dose of sodium oxybate and 200-mg daily dose of modafinil for 22 days. These researchers reported that pitolisant had no effect on sodium oxybate or modafinil pharmacokinetics profile and that sodium oxybate has “no clinically relevant effect on the pharmacokinetic profile of pitolisant.” They added that even though exposure to pitolisant dropped, there was no need to adjust the dose.
• Doghramji and colleagues also reported on a 12-month open-label, phase 3, real-world study where 68 men took either pitolisant, pitolisant with psychostimulants, pitolisant with anticataleptics or pitolisant with psychostimulants and anticataleptic. “Pitolisant was effective both as monotherapy and in combination therapy with sodium oxybate, modafinil and other common medications used in patients with narcolepsy,” these researchers wrote.
• Interim data from 208 patients (mean age, 40.3 years; 63% women, 74.5% white, 59.1% with narcolepsy type 1; 98.1% previously treated with other narcolepsy medications) show the most commonly reported adverse events were headache, anxiety and nausea. These events occurred in 9% or fewer of all patients, were considered “generally mild or moderate in intensity and often occurred early in treatment,” Eric D. Bauer of clinical operations at Harmony Biosciences and colleagues wrote.

Harmony Biosciences seeks FDA approval for pitolisant by the end of the year, according to a company press release. The American Academy of Sleep Medicine estimates that fewer than 1% of the population has narcolepsy. – by Janel Miller

References:

Bauer ED, et al. The safety and tolerability of pitolisant in the treatment of excessive daytime sleepiness and cataplexy in adult patients with narcolepsy: An open-label, expanded access program in the United States.

Dayno JM, et al. Evaluation of abuse potential of the narcolepsy medication pitolisant.

Doghramji K, et al. Pitolisant in combination with other medications for the management of narcolepsy.

Kallweit U, Triller A. Effects of pitolisant on nighttime sleep.

Scart-Grès C, et al. Safety and tolerability of pitolisant in the treatment of adults with narcolepsy: integrated data from clinical studies.

All presented at: SLEEP 2019; June 8-12, San Antonio

Also:

American Academy of Sleep Medicine Fact Sheet on Narcolepsy. https://aasm.org/resources/factsheets/narcolepsy.pdf. Accessed July 1, 2019.
Calik MW. Nat Sci Sleep. 2017; doi:10.2147/NSS.S103462

Disclosures: Healio Primary Care was unable to determine the researchers’ relevant financial disclosures prior to publication.