Harmony Biosciences Holdings Inc released topline results from the INTUNE study of pitolisant for idiopathic hypersomnia (IH), revealing that the primary endpoint for excessive daytime sleepiness did not achieve statistical significance against a placebo in the randomized withdrawal phase.

Further data analysis is ongoing to inform next steps. According to a release from the company, the totality of evidence from the INTUNE study, in which pitolisant demonstrated clinically meaningful benefit in patients completing the initial open-label phase, and the Orphan Drug Designation for pitolisant provide optimism for next steps with the US Food and Drug Administration (FDA).

The INTUNE study was a phase 3 placebo-controlled, double-blind, randomized withdrawal study. Approximately 83% of patients who completed the eight-week open-label treatment period with pitolisant were responders and experienced a robust clinical response, with an average Epworth Sleepiness Scale change from baseline of –9.4 points. 

A positive trend favoring pitolisant was observed during the four-week double-blind randomized withdrawal period; however, no statistically significant difference was observed between pitolisant and placebo groups on Epworth Sleepiness Scale, the primary endpoint. 

Positive trends favoring pitolisant were observed across additional prespecified endpoints including the Hypersomnia Severity Scale, which approached statistical significance, as well as on the Sleep Inertia Questionnaire. Further data analyses are being conducted. Approximately 88% of patients in the study continued into a 12-month long-term extension study, which is ongoing. 

The safety and tolerability profile of pitolisant in adult patients with IH was consistent with the established safety profile and no new safety signals were observed.

“We are very encouraged by the magnitude of the response seen in the initial open-label treatment period, where 83% of patients completing this phase responded with an average 9.4 point improvement in the Epworth Sleepiness Scale. Equally encouraging is the number of patients, almost 90%, electing to continue into the long-term extension study, allowing us to generate additional safety and efficacy data in this patient population. Positive trends in other important outcomes like sleep inertia add to the totality of evidence that pitolisant has a clinical benefit for patients with IH,” says Kumar Budur, MD, chief medical officer at Harmony Biosciences, in a release. 

Budur adds in the release, “We are grateful to the patients, family members, and clinicians who participated in the INTUNE study. We remain committed to the IH patient community and understand their strong desire for a non-scheduled treatment option for IH. Following a thorough review of the full data set, we will work closely with the FDA to discuss next steps and a path forward for pitolisant in IH.”

Pitolisant is marketed as WAKIX in the US for the treatment of excessive daytime sleepiness or cataplexy in adult patients with narcolepsy. Pitolisant is not approved for IH and is currently being evaluated as an investigational agent in adult patients with IH.

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