Alkermes announced positive topline results from a phase 2 study of its oral orexin 2 receptor (OX2R) agonist, alixorexton, in patients with narcolepsy type 1 (NT1).
In the randomized double-blind treatment period of the phase 2 Vibrance-1 study, all doses tested (4 mg, 6 mg, and 8 mg) met the primary endpoint — the Maintenance of Wakefulness Test (MWT) — demonstrating significant, clinically-meaningful, dose-dependent improvements in mean sleep latency compared to the baseline. The trial also met the secondary endpoint of the Epworth Sleepiness Scale (ESS) at all doses at week six, and the Weekly Cataplexy Rates (WCR) was statistically significant at the 6 mg dose.
The results demonstrate the potential for OX2R agonists in NT1 treatment, particularly because Vibrance-1 shows improvements in symptoms other than wakefulness, including fatigue and cognition in narcolepsy. Takeda has also recently shared positive results from two phase 3 trials testing its OXR2 agonist, oveporexton, for treatment of NT1.
Alkermes says its data support "rapid initiation" of a global phase 3 program of alixorexton in patients with NT1. The company plans to share the Vibrance-1 phase 2 safety and efficacy results in an oral presentation at the World Sleep Congress in Singapore in September 2025. In addition to being studied as treatment for NT1, alixorexton is in development for narcolepsy type 2 and idiopathic hypersomnia.