P033 Vibrance-3: safety and efficacy of Alixorexton (ALKS 2680) in idiopathic hypersomnia

Abstract Introduction Alixorexton is a highly potent, oral, selective orexin 2 receptor agonist being developed as a once-daily treatment for narcolepsy and idiopathic hypersomnia (IH). IH is a chronic neurological disorder characterized by excessive daytime sleepiness, among other symptoms. In a phase 1b study in patients with IH, alixorexton demonstrated statistically significant, clinically meaningful improvements in mean sleep latency on the Maintenance of Wakefulness Test and was generally well-tolerated with no serious or severe treatment-emergent adverse events (TEAEs). The phase 2 Vibrance-3 study (NCT06843590) aims to assess the safety and efficacy of alixorexton in patients with IH. Methods Vibrance-3 is a randomized, double-blind, parallel-group, dose-range-finding study. After a 2-week washout, approximately 96 patients with IH will be randomized 1:1:1:1 to receive placebo or alixorexton once daily (10, 14, or 18 mg) for 8 weeks. Eligible patients are aged 18-70y with an IH diagnosis per ICSD-3-TR criteria, BMI ≥18 and ≤ 40 kg/m2, no significant comorbid sleep-related illness that may influence the sleep–wake cycle, no unstable medical conditions, and no shift work or activities that interfere with regular nighttime sleep. The primary endpoint is change in Epworth Sleepiness Scale score, and the key secondary endpoint is change in Idiopathic Hypersomnia Severity Score (both from baseline to week 8). Safety evaluations include TEAEs, laboratory assessments, vital signs, electrocardiograms, and the Columbia-Suicide Severity Rating Scale. Results Vibrance-3 results are pending study completion. Discussion Results from Vibrance-3 will inform clinical development of alixorexton in patients with IH.