HARMONY Biosciences presented data from its Phase 2 signal detection study showing that pitolisant reduced excessive daytime sleepiness (EDS) and fatigue in adults with Myotonic dystrophy Type 1 (DM1). Notably, there was greater mean improvement from baseline to Week 11 in both EDS (as measured by the Daytime Sleepiness Scale) and fatigue (as measured by the Fatigue Severity Scale) compared to placebo. The overall disease burden also signaled greater improvement for pitolisant compared to placebo, with the higher dose pitolisant group showing a stronger efficacy signal.

This study was designed for signal detection and was not powered to demonstrate statistical significance. 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. The Phase 2 signal detection study was a randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of pitolisant in the treatment of EDS and other non-muscular symptoms in adults with DM1.

Eligible patients were confirmed to have DM1 and enrolled in an 11-week double-blind treatment phase that included a 3-week titration period and an 8-week stable dose period. Participants were randomized to receive higher or lower dose pitolisant, or a matching placebo. The primary efficacy endpoint was the change from baseline to Week 11 in Daytime Sleepiness Scale score.

Additional efficacy endpoints included the change from baseline to Week 11 in Epworth Sleepiness Scale score, Fatigue Severity Scale score, Clinical Global Impression of Severity (for EDS) score, and Myotonic Dystrophy Health Index score. Results from the study include: Mean improvement on the Daytime Sleepiness Scale (primary endpoint) was greater for pitolisant. Compared with placebo, a dose-response relationship was observed from baseline to Week 11: Higher Dose Pitolisant (n=8): -2.5, Lower Dose Pitolisant (n=8): -1.0, Placebo (n=9): -0.2. Mean improvement on the other secondary efficacy endpoints (EDS, fatigue, disease burden) was also greater for pitolisant versus placebo, with higher dose pitolisant showing a stronger efficacy signal from baseline to Week 11.

Epworth Sleepiness Scale: Higher Dose Pitolisant (n=8): -4.9, Lower Dose Pitolisant (n=9): 1.3, Placebo (n=10): -0.1. Fatigue Severity Scale: Higher Dose Pitolisant (n=8): -0.9, Lower Dose Pitolisant (n=9): -0.4, Placebo (n=10): -0.1. Clinical Global Impression of Severity (for EDS): Higher Dose Pitolisant (n=8): -0.9, Lower Dose Pitolisant (n=9): -0.2, Placebo (n=10): -0.1. Myotonic Dystrophy Health Index Higher Dose Pitolisant (n=8): -9.1, Lower Dose Pitolisant (n=9): -2.9, Placebo (n=10): 0.4. The rate of adverse events was similar for pitolisant and placebo. The safety and tolerability of pitolisant in patients with DM1 were consistent with its known safety profile. Pitolisant is marketed as WAKIX® in the U.S. and is FDA approved to treat EDS or cataplexy in adult patients 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. 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. 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. WAKIX is indicated for the treatment of excessive daytime sleepiness or cataplexy in adult patients with narcolepsy.