This phase 2 RCT (Vibrance-1) evaluated once-daily oral alixorexton (4 mg, 6 mg, or 8 mg) vs. placebo over 6 weeks in 92 adults aged 18–70 with narcolepsy type 1, with an optional 7-week open-label extension, across 46 sites in the USA, Europe, and Australia.
All three doses significantly improved mean sleep latency (MSL) on the Maintenance of Wakefulness Test (MWT) vs. placebo at week 6: placebo-corrected gains of 22.2 min (4 mg), 24.1 min (6 mg), and 26.0 min (8 mg). Observed MSL was only 2.3 min for placebo vs. 24.0–28.2 min for alixorexton. Common adverse events included pollakiuria (55%), insomnia (28%), salivary hypersecretion (25%), micturition urgency (14%), blurred vision (14%), and hyperhidrosis (7%).
- Small sample size (n=92 total; ~23 per arm) limits precision and generalizability. - Short treatment duration (6 weeks) does not capture long-term efficacy or safety. - Industry-funded (Alkermes), introducing potential sponsorship bias.
Alixorexton, a selective OX2R agonist, produced large, statistically significant improvements in wakefulness in narcolepsy type 1 at all doses tested — but this is a phase 2 study; clinicians should await phase 3 data before adopting it. Anticipate on-target autonomic side effects (urinary urgency, excess salivation, sweating) that may need counseling.
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