Enrollment for Phase 3 INTUNE Study of Pitolisant in Idiopathic Hypersomnia Ahead of Schedule

Author(s):

Pitolisant, a therapy approved for patients with narcolepsy, is currently being assessed in 200 individuals with idiopathic hypersomnia, with change in excessive daytime sleepiness as the primary outcome.

Kumar Budur, MD, MS

Harmony Biosciences announced that enrollment for the phase 3 INTUNE study (NCT05156047) assessing pitolisant (Wakix) in patients with idiopathic hypersomnia is 9 months ahead of schedule, with topline findings anticipated to be reported in the fourth quarter of 2023.¹

INTUNE, a double-blind, placebo-controlled trail spanning 58 clinical sites in the US, assesses the efficacy and safety of pitolisant in 200 adults with IH, a condition traditionally treated with off-label, wake-promoting products. Announced in April 2022, the trial consists of a screening period, an 8-week open-label phase, and a 4-week double-blind randomized withdrawal phase.

"Completing enrollment in the INTUNE study now puts us nine months ahead of plan and reflects the strong interest and enthusiasm from patients and healthcare professionals alike, the unmet medical need in the IH community, and the strong momentum of our broader pitolisant development program,” Kumar Budur, MD, MS, chief medical officer, Harmony Biosciences, said in a statement.¹ "At Harmony, we are harnessing a mechanism-based approach to the development of pitolisant, which is thought to target the histamine system to promote wakefulness in the brain. This approach is driven by our shared conviction that innovative science translates into therapeutic possibilities that have the potential to impact the lives of individuals with rare neurological diseases."

Pitolisant is a novel selective histamine 3(H3) receptor antagonist/inverse agonist that increases the synthesis and release of wake-promoting histamine via a once-daily, oral administration. It remains the only FDA-approved treatment for both excessive daytime sleepiness (EDS) and cataplexy in narcolepsy that is not a controlled substance. It first gained FDA greenlight for EDS in 2019 and later for cataplexy in the following year.

In the open-label phase of INTUNE, patients will be titrated to their optimal dose based on investigator assessment of tolerability and efficacy for 3 weeks, followed by 3 weeks of flexible dosing, and a 2-week stable dose period. During the flexible dosing period, patients will continue to receive their optimal dose of 17.8 mg or 35.6 mg open-label pitolisant, although those taking a CYP2D6 inhibitor will be allowed a maximum permitted daily dose of 17.8 mg.

The trial’s primary outcome measure is change in EDS, as demonstrated by scores on Epworth Sleepiness Scale over the 12-week treatment period. Other secondary outcomes include impact on symptoms of IH, assessed through Idiopathic Hypersomnia Severity Scale, Patient Global Impression of Change, and Clinician Global Impression of Severity. The study will also assess other factors such as sleep-related impairments, sleep inertia, working memory, attention, and psychomotor function.

After completion of the double-blind randomized withdrawal phase, patients will complete 2 safety follow-up telephone contacts at 15 and 30 days after their final dose of blinded study drug. This will include assessments for AEs and concomitant medication use, as well as an opportunity to enter into a long-term, open-label safety study under a separate protocol. Patients who opt to enroll into the open-label study are not required to complete the 15-day and 30-day follow-up calls.

REFERENCE
1. Harmony Biosciences completes enrollment of phase 3 registrational INTUNE study in idiopathic hypersomnia. News release. May 25, 2023. Accessed May 26, 2023. https://www.prnewswire.com/news-releases/harmony-biosciences-completes-enrollment-of-phase-3-registrational-intune-study-in-idiopathic-hypersomnia-301834132.html