Amee Revana, DO, FAASM: Pitolisant Reduces Sleepiness in Prader-Willi Syndrome

News
Video

At SLEEP 2024, Revana told HCPLive her thoughts on the potential of pitolisant to address excessive daytime sleepiness in Prader-Willi syndrome compared to treating narcolepsy.

Phase 2 data showed pitolisant (wakix) may reduce excessive daytime sleepiness in patients with Prader-Willi syndrome.1

Pitolisant, in a class of medications called H3 blockers, is an approved medication to treat excessive daytime sleepiness caused by narcolepsy or cataplexy. Since patients with Prader-Willi syndrome often have excessive daytime sleepiness too, investigators wanted to see if pitolisant also reduced sleepiness in this group of people.

Prader-Willi syndrome is a genetic, neurodevelopmental disorder characterized by global hypothalamic dysfunction. According to the Mayo Clinic, symptoms of this syndrome include food craving and weight gain (hyperphagia), underdeveloped sex organs, poor growth and physical development, cognitive impairment, delayed motor development, speech problems, behavioral problems, and sleep disorders.2 Other symptoms may include small hands and feet, scoliosis, hip issues, reduced saliva flow, nearsightedness or other vision issues, problem regulating body temperature, a high pain tolerance, and hypopigmentation affecting hair, eyes, and skin.

A phase 2 study, led by Amee Revana, DO, FAASM, found trends of pitolisant reducing excessive daytime sleepiness in patients with Prader-Willi Syndrome, compared to patients on placebo.1

“This could be life altering for these patients,” Amee Revana, DO, FAASM, from Baylor College of Medicine and Texas Children's Hospital, told HCPLive at SLEEP 2024, the 38th annual meeting of the Associated Professional Sleep Societies.

Pitolisant contains histamine, a neurotransmitter targeting wakefulness in Prader-Willi syndrome.

“For Prader-Willi syndrome, that is a key feature as far as symptoms of excessive daytime sleepiness, so we hope to improve their overall quality of life, their excessive daytime sleepiness, and others another features of narcolepsy in in that population,” Revana said.

Expanding off the research, a multicenter, randomized, double-blind, placebo-controlled phase 3 study with a larger sample is already underway with participant enrollment beginning in April 2024 and research sites now worldwide. Revana presented the aims and methodology as a late breaker at SLEEP 2024.

The phase 3 trial will assess the efficacy and safety of pitolisant in patients with Prader-Willi syndrome. Patients (≥ 100) have to be ≥ 6 years old with a confirmed diagnosis of Prader-Willi syndrome and excessive daytime sleepiness.

Participants will be randomized 1:1 to receive pitolisant (weight-based dosing: 8.9-44.5 mg/d) or placebo. An optional 52-week open-label extension will follow the 11-week double-blind period.

In the interview Revana explained how no standard of care exists for Prader-Willi syndrome. She hopes the study will demonstrate how pitolisant not only improves the excessive daytime sleepiness but helps improve other symptoms of the syndrome too.

However, even if pitolisant does get approved for improving Prader-Willi syndrome symptoms, diagnosing barriers will persist.

“Prader-Willi syndrome is not always the first feature or symptom that most patients will pick up on, or identify as a problem, usually [it is] a type of aphasia, early onset obesity, developmental issues,” Revana said. “And so, sometimes getting to that diagnosis of narcolepsy-type features or identifying some of those symptoms will be difficult. This is one of the reasons why we are trying to advocate internationally to identify as many of these patients as possible.”

Relevant Disclosures for Revana include Harmony Biosciences.

References

  1. Revana, A, Seiden, D, Rapchak, K, et al. 0648 Phase 3 Randomized Placebo-Controlled Trial of Pitolisant for Excessive Daytime Sleepiness in Prader-Willi Syndrome, Sleep, Volume 47, Issue Supplement_1, May 2024, Page A277, https://doi.org/10.1093/sleep/zsae067.0648
  2. Prader-Willi Syndrome. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/prader-willi-syndrome/symptoms-causes/syc-20355997. Accessed June 3, 2024.
Related Videos
Ralph DeFronzo, MD | Credit: UT San Antonio
Signs and Symptoms of Connective Tissue Disease
Timothy Garvey, MD | Credit: University of Alabama at Birmingham
3 KOLs are featured in this program.
3 KOLs are featured in this program.
Atul Malhotra, MD | Credit: Kyle Dykes; UC San Diego Health
Edward V Loftus, Jr, MD | Credit: Mayo Clinic
Katie Ross-Driscoll, PhD, MPH | Credit: Regenstrief Institute
Video 3 -  4 KOLs are featured in, "Collaborating with Specialists: Primary Care Clinician’s Evolving Role in HE Management"
© 2024 MJH Life Sciences

All rights reserved.