Harmony Biosciences Shares Positive Pitolisant Data for Myotonic Dystrophy Type 1

Harmony Biosciences presented encouraging data from its Phase 2 study on the efficacy of pitolisant in reducing excessive daytime sleepiness (EDS) and fatigue in adults with Myotonic dystrophy Type 1 (DM1) at the annual SLEEP 2024 conference. Dr. Kumar Budur, the company's Chief Medical and Scientific Officer, highlighted the significant impact of EDS and fatigue on DM1 patients, noting that these symptoms are nearly as debilitating as the primary symptoms of myotonia and muscle weakness.

The study demonstrated a greater mean improvement in both EDS and fatigue for patients treated with pitolisant compared to those given a placebo. These improvements were measured using the Daytime Sleepiness Scale and the Fatigue Severity Scale, respectively. The higher dose pitolisant group exhibited a stronger efficacy signal, despite the study being designed for signal detection rather than demonstrating statistical significance.

There are currently an estimated 40,000 people in the U.S. diagnosed with DM1, with up to 90% reporting symptoms of EDS and fatigue. Due to the promising results of the Phase 2 study, Harmony Biosciences plans to advance to a pivotal Phase 3 study using the Next-Generation 2 (NG2) formulation of pitolisant. This formulation is designed to optimize pharmacokinetics and deliver higher dosage strengths, potentially benefiting over 100,000 patients with unmet medical needs if the lifecycle management programs are successful.

The Phase 2 study was a randomized, double-blind, placebo-controlled trial that involved an 11-week treatment phase, including a 3-week titration period and an 8-week stable dose period. Participants were randomized to receive either a higher or lower dose of pitolisant or a matching placebo. The primary efficacy endpoint focused on the change from baseline to Week 11 in the Daytime Sleepiness Scale score, while additional endpoints included changes in the Epworth Sleepiness Scale score, Fatigue Severity Scale score, Clinical Global Impression of Severity for EDS score, and Myotonic Dystrophy Health Index score.

The study's results revealed mean improvements on the Daytime Sleepiness Scale for higher dose pitolisant (-2.5) and lower dose pitolisant (-1.0) compared to placebo (-0.2). Similar trends were observed across secondary endpoints, with the higher dose pitolisant group showing notably better outcomes.

Safety and tolerability for pitolisant in DM1 patients were consistent with its known safety profile, with adverse events rates similar between the pitolisant and placebo groups. Pitolisant, marketed as WAKIX® in the U.S., is FDA-approved for treating EDS or cataplexy in adults with narcolepsy but remains investigational for DM1.

Myotonic dystrophy Type 1 (DM1) is the most common form of adult-onset muscular dystrophy, inherited in an autosomal-dominant pattern. It affects approximately one in 2,100 individuals, equating to about 150,000 people in the U.S.

WAKIX®, a first-in-class medication, functions as a selective histamine 3 (H₃) receptor antagonist/inverse agonist, promoting wakefulness. Commercially available in the U.S. since late 2019, it has been granted various designations by the FDA for treating narcolepsy and cataplexy. WAKIX's mechanism is thought to involve increasing the release of histamine, a neurotransmitter that promotes wakefulness. Developed by Bioprojet in France, Harmony Biosciences holds an exclusive license to develop, manufacture, and commercialize pitolisant in the United States.