Positive topline results from Harmony Biosciences’ phase 2 signal detection study evaluating the safety and efficacy of pitolisant in adult patients with myotonic dystrophy type 1 showed clinically meaningful improvements in the primary efficacy endpoint of excessive daytime sleepiness, as well as fatigue, a secondary endpoint.

Excessive daytime sleepiness and fatigue occur in up to 80-90% of patients with myotonic dystrophy type 1 and impact daily functioning as much as muscular symptoms (myotonia and muscle weakness).   

“These strong topline results add to the body of evidence supporting the effectiveness of pitolisant for improving EDS,” says Jeffrey M. Dayno, MD, president and CEO of Harmony Biosciences, in a release. “In addition, a positive signal for pitolisant has been demonstrated for fatigue, suggesting it could be a potential new treatment option for this symptom as well. We are encouraged by these results, which underscore our commitment to translating innovative science into therapeutic possibilities for patients living with unmet medical needs.”

Topline results include:

  • Clinically meaningful improvements were demonstrated in excessive daytime sleepiness as measured by Daytime Sleepiness Scale, Epworth Sleepiness Scale, and Clinical Global Impression of Severity of excessive daytime sleepiness.
    • On Daytime Sleepiness Scale, the mean change from baseline to end of double-blind period was -2.5 and -1.0 for the higher dose and lower dose pitolisant treatment groups, respectively, compared to -0.2 for placebo.
    • On Epworth Sleepiness Scale, the mean change from baseline to end of double-blind period was -4.88 for the higher dose pitolisant treatment group compared to -0.10 for placebo.
    • On Clinical Global Impression of Severity, the mean change from baseline to end of double-blind period was -0.9 for the higher dose pitolisant treatment group compared to -0.1 for placebo.
  • Clinically meaningful improvements were demonstrated for fatigue as measured by the Fatigue Severity Scale.
    • On Fatigue Severity Scale, the mean change from baseline to end of double-blind period was -0.86 and -0.36 for the higher dose and lower dose pitolisant treatment groups, respectively, compared to -0.13 for placebo.
  • A clear and consistent dose-response was demonstrated with the higher dose pitolisant group showing a greater response than the lower dose group across the study endpoints.
  • Safety and tolerability profile in adult patients with myotonic dystrophy type 1 was consistent with the established safety profile of pitolisant with no new safety signals detected and no serious adverse events reported.

This phase 2 signal detection study was a randomized, double-blind, placebo-controlled study in adults ages 18-65 with myotonic dystrophy type 1. This study was not powered to demonstrate statistical significance. Thirty patients were randomized at baseline to receive lower dose pitolisant, higher dose pitolisant, or placebo in a 1:1:1 treatment ratio titrated over three weeks, followed by eight weeks of stable dosing.

“These positive signals for pitolisant are promising news for the [myotonic dystrophy type 1] patient community, where 80-90% of the approximately 40,000 diagnosed [myotonic dystrophy type 1] patients in the US experience significant excessive daytime sleepiness and fatigue with no FDA-approved treatments available,” says Kumar Budur, MD, MS, chief medical officer at Harmony Biosciences, in a release. “The strong signals for pitolisant reinforce our confidence in it as a potential treatment option worthy of further study in patients with [myotonic dystrophy type 1] .”

The full dataset from the trial will include findings from other secondary outcomes, including the Myotonic Dystrophy Health Index, cognitive functions, and the safety and effectiveness of pitolisant from the ongoing Open-Label Extension phase. Additional results from the trial will be shared early next year, according to a release from Harmony Biosciences, which notes that detailed results will be presented at an upcoming medical meeting and will be submitted for publication.

Pitolisant is marketed as Wakix in the US and is FDA-approved to treat excessive daytime sleepiness or cataplexy in adults with narcolepsy. Pitolisant is not approved for use in patients with myotonic dystrophy type 1 and is currently being evaluated as an investigational agent in this patient population.

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