Harmony Biosciences Holdings, Inc. announced positive topline results from its Phase 2 signal detection study evaluating the safety and efficacy of pitolisant in adult patients with myotonic dystrophy type 1 (DM1). A clinically meaningful improvement was demonstrated on the primary efficacy endpoint, the change from baseline to the end of the double-blind period for excessive daytime sleepiness (EDS) as measured by the Daytime Sleepiness Scale (DSS). A clinically meaningful improvement was also demonstrated for fatigue, a secondary efficacy endpoint measured by the Fatigue Severity Scale (FSS).

EDS and fatigue occur in up to 80-90% of patients with DM1 and impact daily functioning as much as muscular symptoms (myotonia and muscle weakness). Topline results include: Clinically meaningful improvements were demonstrated in EDS as measured by DSS, Epworth Sleepiness Scale (ESS), and Clinical Global Impression of Severity (CGI-S) of EDS. On DSS, 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 ESS, 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 CGI-S, 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 (FSS).

On FSS, 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 DM1 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 DM1. 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.

The full dataset from this trial will include findings from other secondary outcomes, including the Myotonic Dystrophy Health Index (MDHI), cognitive functions, and the safety and effectiveness of pitolisant from the ongoing Open-Label Extension (OLE) Phase. Additional results from the trial will be shared early next year. Detailed results will be presented at an upcoming medical meeting and will be submitted for publication.

Pitolisant is marketed as WAKIX® in the U.S. and is FDA approved to treat excessive daytime sleepiness or cataplexy in adults with narcolepsy. Pitolisant is not approved for use in patients with DM1 and is currently being evaluated as an investigational agent in this patient population. About Myotonic Dystrophy Type 1: Myotonic dystrophy Type 1 (DM1) is the most common form of adult-onset muscular dystrophy.

It is a genetic disorder inherited in an autosomal-dominant pattern. Latest estimates suggest a prevalence of about one per 2,100 people with the genetic defect for DM1. This equates to about 150,000 people in the U.S. with the genetic defect for DM1.

Estimates suggest there are 40,000 people currently diagnosed with DM1 in the U.S., with up to 90% of them reporting EDS and fatigue and over 60% of them experiencing cognitive dysfunction. About WAKIX® (pitolisant) Tablets: WAKIX, a first-in-class medication, is approved by the U.S. Food and Drug Administration for the treatment of excessive daytime sleepiness or cataplexy in adult patients with narcolepsy and has been commercially available in the U.S. since Fourth Quarter 2019. It was granted orphan drug designation for the treatment of narcolepsy in 2010, and breakthrough therapy designation for the treatment of cataplexy in 2018.

WAKIX is a selective histamine 3 (H3) receptor antagonist/inverse agonist. The mechanism of action of WAKIX is unclear; however, its efficacy could be mediated through its activity at H3 receptors, thereby increasing the synthesis and release of histamine, a wake promoting neurotransmitter. WAKIX was designed and developed by Bioprojet (France).

Harmony has an exclusive license from Bioprojet to develop, manufacture and commercialize pitolisant in the United States.