Phase 2 Trial Launched to Test Pitolisant for Excessive Sleepiness in PWS

Harmony Biosciences has kicked off a Phase 2 clinical trial to evaluate the safety and effectiveness of pitolisant to treat excessive daytime sleepiness in people with Prader-Willi syndrome, ages 6 to 65.

The study (NCT04257929) is expected to start enrolling participants soon, the company said in a press release.

Pitolisant enhances the activity of histaminergic neurons, a type of nerve cell that helps fight uncontrollable sleepiness, or narcolepsy. It works by blocking the histamine 3 (H₃) receptor, increasing the production and release of histamine, a neurotransmitter that regulates the sleep-wake system and promotes wakefulness. Neurotransmitters are molecules that enable nerve cell communication.

The therapy was approved by the U.S. Food and Drug Administration in August 2019, under the brand name Wakix, to treat excessive daytime sleepiness in adults with narcolepsy.

Pitolisant’s potential in Prader-Willi Syndrome (PWS) was first identified by the Chion Foundation, which works to raise awareness and improve the lives of patients with this and other rare conditions.

The foundation’s president and co-founder, Lara C. Pullen, PhD, paved the way by alerting to the fact that sleep problems in those with PWS, often neglected in clinical care and research, are more common than previously thought and represent an opportunity to develop therapies with a potential significant impact on patients’ lives.

“There is no denying that hunger and obesity are problems in the PWS community,” Pullen said in the release. “The thing is that the pharmaceutical community has not yet been able to deliver a drug that relieves those symptoms of PWS and improves the quality of lives of patients with PWS and their families. We think that a different strategy, tackling sleepiness, may be able to achieve all of those goals.”

Working with the TREND community, researchers led by Pullen previously reported on the experience of PWS children with narcolepsy complaints who began therapy with pitolisant. Overall, the treatment improved sleep patterns, making the children sleep more during the night and more active during the day.

“We analyzed caregiver conversations in private Facebook groups and our findings validated Lara’s hypothesis,” said Maria Picone, CEO and co-founder of TREND, and co-founder of the Chion Foundation. “The PWS community frequently discuss issues related to sleep. In fact, terms associated with sleep were used far more often than terms for hunger.”

In the Phase 2 study, approximately 60 patients will be randomly assigned to once daily dosing (in the morning, after waking up) with a low or high dose of pitolisant, or a matching placebo.

The study will entail a 11-week double-blind treatment phase, including a three-week titration period — in which the therapy’s dose will be slowly adjusted to the intended amount — and an eight-week stable dose period. Eligible patients will be given the opportunity to participate in an open-label extension phase, in which all participants will go through a three-week period to reach maximum dose of pitolisant based on their age.

Notably, this extension phase is expected to last several years and to continue until pitolisant is approved for people with PWS or Harmony decides to terminate the trial.

The study’s primary goal will be changes in excessive daytime sleepiness, from baseline to week 11, measured through the sleep latency test, which records one’s tendency to fall asleep. Other goals include assessing clinical symptoms, behavior, psychomotor function, and caregiver burden.

For more contact information about the trial, go here.