Dr Jeffrey DaynoJeffrey Dayno, MD
Pitolisant, a selective histamine 3 receptor antagonist/inverse agonist developed by Harmony Biosciences, was recently approved under the brand name Wakix for the treatment of excessive daytime sleepiness in adults with narcolepsy. The agent was not deemed a controlled substance by the DEA—the first narcoleptic therapy to be void of that scheduling.1

As there is an ongoing need for better and more effective medications in sleep disorders such as narcolepsy, the door was open for agents like pitolisant to enter the market. It has been shown to be generally safe and well-tolerated, based on pooled safety data from 4 placebo-controlled trials totaling more than 300 patients.2

In clinical trials, the therapy has shown to be quite effective. In a 5-year dataset, patients experienced drops in Epworth Sleepiness Scale (ESS) scores of 3.4 points (to 13.4) through 12 months, and 6.2 points (to 10.6) by year 5. The data also show reductions of multiple symptoms of REM dysregulation, a 76% reduction in the symptoms of cataplexy, a 62% reduction in sleep paralysis, and a 54% reduction in hypnagogic hallucinations from baseline to year 1.3

To learn more about the therapy’s advantages, NeurologyLive sought comment from Jeffrey Dayno, MD, chief medical officer, Harmony Biosciences, and John C. Jacobs, MBA, chairman and CEO, Harmony Biosciences. The pair provided some insight into what to expect now that pitolisant is approved.

NeurologyLive: What does this approval offer physicians treating narcolepsy?

John C. Jacobs, MBA: Wakix provides healthcare professionals managing people living with narcolepsy a new and important treatment option for their patients. While there are medications on the market approved for narcolepsy, Wakix is the first and only FDA-approved non-scheduled product for narcolepsy.

Is there a specific subgroup of patients with narcolepsy in which pitolisant can make an impact?

Jeffrey Dayno, MD: There are up to 200,000 Americans living with narcolepsy, all of whom have excessive daytime sleepiness. Wakix is the first and only FDA approved non-scheduled product for narcolepsy, and it offers an important benefit/risk profile to address the unmet medical need that exists in people living with narcolepsy.

Could you expand on the risk-benefit profile offered by pitolisant, and what particular unmet needs will be aided by its approval?

Jeffrey Dayno, MD: While there are medications on the market approved for narcolepsy, Wakix is the first and only FDA approved non-scheduled product for narcolepsy.  It is a first-in-class medication with a novel mechanism of action, that works through a natural chemical in the brain, histamine, a major wake-promoting neurotransmitter.

The efficacy of Wakix for the treatment of EDS in adult patients with narcolepsy was evaluated in two multicenter, randomized, double-blind, placebo-controlled studies, HARMONY 1 and HARMONY 1bis. These studies included a total of 261 patients who were randomized to receive Wakix, placebo, or active control; these patients had a median age of 37 (in HARMONY 1) and 40 (in HARMONY 1bis). Treatment duration was 8 weeks, with a three-week dose titration phase followed by a 5-week stable dose phase; 75% to 80% of the patients in these studies had a history of cataplexy. In both of these studies, Wakix demonstrated a statistically significant improvement in EDS as measured by the ESS score.

In the placebo-controlled trials conducted in patients with narcolepsy with or without cataplexy, the most common adverse reactions (occurring in ≥5% of patients and at twice the rate of placebo) with the use of Wakix were insomnia (6%), nausea (6%), and anxiety (5%).

What will the dosing variations of the therapy be, and when will it be available?

Jeffrey Dayno, MD: The recommended dose range for Wakix is 17.8 mg to 35.6 mg administered orally once daily in the morning upon wakening. Wakix will be commercially available to healthcare professionals and appropriate patients in the US in the fourth quarter of 2019.

Transcript adjusted for clarity.
REFERENCES
1. WAKIX represents the first and only non-scheduled treatment approved for patients with narcolepsy in the U.S. [press release]. Plymouth Meeting, PA: Harmony Biosciences; August 15, 2019. finance.yahoo.com/news/harmony-biosciences-announces-fda-approval-120000845.html. Accessed August 15, 2019.
2. Scart-Grès C, Momah C, Roy M, Maski K,  Piris S, Bogan RK. Sleep. 2019;42(Suppl 1):A244–A245. doi: 10.1093/sleep/zsz067.612. Presented at: SLEEP 2019. June 8-12, 2019; San Antonio, TX. Abstract 0614.
3. Harmony Biosciences presents 5-year data on pitolisant at international narcolepsy symposium [news release]. Plymouth Meeting, PA: Harmony Biosciences; September 11, 2018. harmonybiosci­ences.com/newsroom/harmony-biosciences-presents-5-year-data-on-pitolisant-at-international. Accessed August 15, 2019.