Another oral OX2R agonist for narcolepsy type 1 clears phase II trial

The novel oral orexin 2 receptor (OX2R) agonist alixorexton has demonstrated clinical benefits in patients with narcolepsy type 1, yielding improvements in wakefulness, excessive daytime sleepiness, and cataplexy, according to the phase II Vibrance-1 trial.

Vibrance-1 included 92 adults (mean age 33.5 years, 62 percent female) with narcolepsy type 1 recruited from 46 hospitals and private research centres across the US, Europe, and Australia. These participants were randomly assigned to receive alixorexton at 4 (n=23), 6 (n=22), or 8 mg (n=24) or placebo (n=23). Treatment was administered orally once daily for 6 weeks, followed by an optional 7-week open-label extension.

The primary endpoint was change in mean sleep latency on the Maintenance of Wakefulness Test (MWT) at week 6. Safety endpoints included treatment-emergent adverse events.

After 6 weeks of treatment, the mean sleep latency on the MWT was 24 min with alixorexton 4 mg, 25.9 min with 6 mg, and 28.2 min with 8 mg vs 2.3 min with placebo. The difference between alixorexton and placebo was significant across all dose groups (p=0.0099 for 4 mg, p<0.0001 for 6 and 8 mg).

Treatment-emergent adverse events (TEAEs) occurred more frequently among alixorexton-treated participants vs placebo recipients. The most common TEAEs in the combined alixorexton group was pollakiuria (55 percent), insomnia (28 percent), salivary hypersecretion (25 percent), micturition urgency (14 percent), blurred vision (14 percent), and hyperhidrosis (7 percent).