Prader-Willi syndrome (PWS) is a rare genetic disorder with a number of physical, emotional, mental, and behavioral manifestations. Individuals with PWS may exhibit cognitive impairment, hypotonia (poor muscle tone), and speech impediments. A prominent feature of PWS is hyperphagia, an insatiable hunger sensation leading to a perpetual feeling of never being full.

However, there are features of PWS that are challenging for families but are often overlooked in research. One of these is the prevalence of sleep disturbances among those affected. An estimated 50% of people with Prader-Willi syndrome deal with excessive daytime sleepiness. Many families want more research to focus on solutions that can help them manage the spectrum of symptoms and complications. 

Orphan Drug Designation

Pitolisant, a selective histamine H3 receptor antagonist developed by Harmony Biosciences, is typically used to treat excessive daytime sleepiness in adults with narcolepsy. But researchers have been looking at pitolisant as a potential treatment option for excessive daytime sleepiness in those with PWS.  

Lindsey Shapiro reports in Prader-Willi News that the U.S. Food and Drug Administration (FDA) recently granted Orphan Drug designation to pitolisant for PWS. Orphan Drug designation was developed to incentivize drug development in the rare disease space. Prior to the Orphan Drug Act of 1983, there were minimal avenues to stimulate drug development and review in this space. Now, Orphan Drug designation provides fee waivers, tax credits, seven years of market exclusivity upon drug approval, and other benefits to those aiming to transform the rare disease landscape. 

For context, rare conditions in the United States are considered any conditions affecting fewer than 200,000 people.

PWS Studies

Previously, researchers evaluated pitolisant for Prader-Willi syndrome in a Phase 2 proof-of-concept study. 65 individuals enrolled. The study found that pitolisant was safe and well-tolerated. Some individuals experienced adverse reactions such as anxiety, headache, or irritability. Ultimately, pitolisant reduced excessive daytime sleepiness in enrolled individuals. The strongest reductions were seen in children between ages six and eleven. More so, pitolisant also reduced behavioral difficulties and hunger. Though the results between pitolisant and the placebo were not statistically significant, these results did catalyze the Phase 3 study.

Currently, Harmony Biosciences is preparing for the upcoming Phase 3 TEMPO study. During the study, researchers will look into how safe and effective pitolisant is on improving behavior and reducing excessive daytime sleepiness in people with PWS. Up to 134 participants will enroll.