Harmony Biosciences Enrolls First Patient in Pitolisant Trial for Excessive Daytime Sleepiness

Harmony Biosciences announced the first patient has been enrolled in a Phase 2 trial evaluating the safety and efficacy of pitolisant for the treatment of excessive daytime sleepiness (EDS) and other key symptoms in patients with Prader-Willi Syndrome (PWS).

"We view pitolisant as a portfolio in a product opportunity and are taking a mechanism-based approach to drug development in managing its life cycle with the goal of expanding its clinical utility," said Harmony's Chief Medical Officer, Jeffrey Dayno, M.D. "We believe pitolisant could offer an important therapeutic benefit in people living with PWS based on preclinical models of the disorder, pitolisant's demonstrated efficacy in improving EDS in patients with narcolepsy, and anecdotal evidence in patients with PWS. We look forward to continuing our collaboration with the Foundation for Prader-Willi Research, the Prader-Willi Syndrome Association USA, and the patient and family community as we advance our development program in order to help address this unmet medical need."

PWS is a genetic orphan/rare neurological disorder with many of the symptoms resulting from hypothalamic dysfunction. The hypothalamus is the part of the brain that controls both sleep-wake state stability and signals that mediate the balance between hunger and satiety. The hypothalamic dysfunction in patients with PWS results in two of the main symptoms of the disorder: EDS and hyperphagia (an abnormally increased appetite for and consumption of food). Other features include low muscle tone, short stature, behavioral problems and cognitive impairment. Approximately 15,000 to 20,000 people in the U.S. live with PWS, and over half of them experience EDS.

"We support and encourage research that can potentially help reduce the symptom burden for children and adults living with PWS. We are grateful that Harmony is studying pitolisant in a clinical trial, which may bring us one step closer to finding an important therapeutic advancement," said John Walter, Chief Executive Officer, Foundation for Prader-Willi Research and Paige Rivard, Chief Executive Officer, Prader-Willi Syndrome Association USA in a joint statement.

The Phase 2 clinical trial is a randomized, double-blind, placebo-controlled study designed to assess the safety and efficacy of pitolisant in patients with PWS ages 6-to-65. An estimated 60-70 patients will be enrolled at approximately 10 sites across the United States. Patients will be randomized to receive one of two doses of pitolisant or placebo for eight weeks of stable dosing following a three-week titration period. The trial's primary objective is to assess improvement in EDS as measured by the Multiple Sleep Latency Test. Topline results are anticipated in the first half of 2022. Patients who complete the trial will be eligible to participate in an open-label extension phase to assess the long-term safety and effectiveness of pitolisant.

"I have seen first-hand the debilitating effects this rare disease can have on patients with Prader-Willi Syndrome," said Dr. Daniel Glaze from Baylor College of Medicine and Texas Children's Hospital, and investigator in the Phase 2 clinical trial. "Excessive daytime sleepiness is more common in patients with PWS than previously appreciated and results in significant impact on daily functioning. In addition, EDS has not been studied in clinical trials to date in patients with PWS. I look forward to participating in this trial to assess the effect of pitolisant on EDS and other related symptoms."

Pitolisant is marketed as WAKIX® in the U.S. for the treatment of EDS or cataplexy in adult patients with narcolepsy.

WAKIX, a first-in-class medication, is approved by the U.S. Food and Drug Administration (FDA) for the treatment of excessive daytime sleepiness or cataplexy in adult patients with narcolepsy. WAKIX has been commercially available in the U.S. since Q4 2019. It was granted orphan drug designation for the treatment of narcolepsy in 2010. 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.