Harmony Biosciences Holdings, Inc. announced that the Company has accelerated the timeline for completing its Phase 3 INTUNE study evaluating the safety and efficacy of pitolisant in adult patients with idiopathic hypersomnia. The Company now expects to complete enrollment in the second quarter of 2023 with topline data anticipated in the fourth quarter of 2023. This, along with the pace of enrollment, confirms the accelerated timeline toward expected completion of the trial.
The INTUNE study is a double-blind, placebo-controlled, randomized withdrawal Phase 3 registrational trial in approximately 200 IH patients being conducted at about 60 clinical trial sites across the U.S. The primary objective is to evaluate the safety and efficacy of pitoliant compared with placebo in treating excessive daytime sleepiness (EDS) in adult patients with IH. IH is one of the central disorders of hypersomnolence and, like narcolepsy, is a debilitating sleep disorder that can result in significant disruption in daily functioning. WAKIX, a first-in-class medication, is approved by the U.S. Food and Drug Administration for the treatment of excessive daytime sleepiness or cataplexy in adult patients with narcolepsy and has been commercially available in the U.S. since Fourth Quarter 2019.
It was granted orphan drug designation for the treatment of narcolepsy in 2010, and breakthrough therapy designation for the treatment of cataplexy in 2018. WAKIX is not recommended in patients with end-stage renal disease (ESRD). In the placebo-controlled clinical trials conducted in patients with narcolepsy with or without cataplexy, the most common adverse reactions (5% and at least twice placebo) for WAKIX were insomnia (6%), nausea (6%), and anxiety (5%).
Other adverse reactions that occurred at 2% and more frequently than in patients treated with placebo included headache, upper respiratory tract infection, musculoskeletal pain, heart rate increased,hallucinations, irritability, abdominal pain, sleep disturbance, decreased appetite, cataplexy, dry mouth, and rash. Concomitant administration of WAKIX with strong CYP2D6 inhibitors increases pitolisant. exposure by 2.2-fold.
Reduce the dose of WAKIX by half. Concomitant use of WAKIX with strong CYP3A4 inducers decreases exposure of pitolisant by 50%. Dosage adjustments may be required.
H1 receptor antagonists that cross the blood-brain barrier may reduce the effectiveness of WAKIX. Patients should avoid centrally acting H1 receptor antagonists. WAKIX is a borderline/weak inducer of CYP3A4.
Therefore, reduced effectiveness of sensitive CYP3A4 substrates may occur when used concomitantly with WAKIX. The effectiveness of hormonal contraceptives may be reduced when used with WAKIX and effectiveness may be reduced for 21 days after discontinuation of therapy.