DUBLIN, June 17, 2026
Alkermes plc announced detailed positive results from the Phase 2 Vibrance-2 clinical trial evaluating alixorexton, an investigational oral selective orexin 2 receptor (OX2R) agonist, in adults with narcolepsy type 2 (NT2). The randomized, double-blind, placebo-controlled study enrolled 93 patients and successfully achieved its dual primary endpoints, demonstrating statistically significant and clinically meaningful improvements in wakefulness measured by the Maintenance of Wakefulness Test (MWT) and reductions in excessive daytime sleepiness measured by the Epworth Sleepiness Scale (ESS) after eight weeks of treatment. Results, presented at SLEEP 2026, also showed that improvements in wakefulness, cognition, and fatigue were maintained through the 13-week study period, while alixorexton was generally well tolerated across all doses tested. The findings represent the first large Phase 2 study of an orexin 2 receptor agonist to demonstrate meaningful clinical benefit in narcolepsy type 2, a patient population without known orexin deficiency.
Sustained Benefits Observed Across Wakefulness, Fatigue, and Cognition
The Vibrance-2 study evaluated once-daily doses of 10 mg, 14 mg, and 18 mg of alixorexton over an eight-week randomized treatment period followed by a five-week open-label extension. Patients receiving alixorexton demonstrated significant increases in mean sleep latency, with participants improving from an average of approximately six minutes at baseline to as much as sixteen minutes on the Maintenance of Wakefulness Test. The treatment also produced meaningful reductions in Epworth Sleepiness Scale scores, moving the majority of patients from severe excessive daytime sleepiness at baseline into the normal or mild sleepiness range by Week 8, with average scores remaining within the normal range by Week 13. Beyond wakefulness, exploratory patient-reported outcomes revealed clinically meaningful improvements in fatigue and cognitive function, including better PROMIS-Fatigue and British Columbia Cognitive Complaints Inventory (BC-CCI) scores. Improvements emerged as early as Week 2 and continued throughout the study, suggesting that alixorexton may provide broad functional benefits beyond reducing daytime sleepiness.
Favorable Safety Profile Supports Continued Development
Safety findings from the Phase 2 study further supported the therapeutic potential of alixorexton. More than 95% of participants completed the eight-week double-blind treatment period, while nearly 90% completed the full 13-week study, reflecting strong treatment adherence. No serious treatment-emergent adverse events were reported, and investigators observed no clinically meaningful safety concerns involving liver function, kidney function, electrocardiograms, ophthalmic examinations, or vital signs. The most frequently reported adverse events—including pollakiuria, insomnia, urinary urgency, dizziness, and headache—were predominantly mild to moderate in severity. The favorable tolerability profile across all tested doses strengthens confidence in the long-term development of alixorexton as a potential treatment for central disorders of hypersomnolence.
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Phase 3 Brilliance Program Underway Following Positive Phase 2 Results
Building on the positive outcomes from both the Vibrance-1 and Vibrance-2 studies, Alkermes has initiated a comprehensive global Phase 3 Brilliance clinical program evaluating once-daily and split-dose regimens of alixorexton in patients with narcolepsy type 1 and narcolepsy type 2. The investigational therapy is also being studied in the Phase 2 Vibrance-3 trial for idiopathic hypersomnia, expanding its potential across multiple sleep disorders. Alixorexton has already received FDA Breakthrough Therapy Designation for narcolepsy type 1, FDA Orphan Drug Designation for idiopathic hypersomnia, and European Commission Orphan Drug Designation for narcolepsy, highlighting growing regulatory recognition of its therapeutic promise. With its novel orexin 2 receptor agonist mechanism, sustained improvements in wakefulness, cognition, and fatigue, and encouraging safety profile, alixorexton is emerging as one of the most promising investigational therapies in the evolving treatment landscape for narcolepsy and hypersomnolence disorders.
Source: Alkermes press release
