Investigational Narcolepsy Drug Shown to Be Effective in Increasing Wakefulness

According to study results presented in The New England Journal of Medicine, treatment with TAK-861 (oveporexton; Takeda, Cambridge, MA) demonstrated significant improvements in wakefulness among adults with narcolepsy type 1. TAK-861 is a selective orexin receptor 2 agonist which crosses the blood-brain barrier.

The randomized, double-blind, placebo-controlled phase 2 clinical trial (NCT05687903) included adults aged 18 to 70 years with a diagnosis of narcolepsy type 1. Participants received either TAK-861 (0.5 mg twice daily [n=23], 2.0 mg twice daily [n=21], 2.0 mg followed by 5.0 mg daily [n=23], 7 mg once daily [n=23]) or a matching placebo (n=23) for 8 weeks. The primary end point was the change in average sleep latency measured by the Maintenance of Wakefulness Test (MWT). Secondary endpoints included changes in Epworth Sleepiness Scale (ESS) scores and weekly cataplexy rates (tracked via participant diaries).

• Average sleep latency on the MWT increased from baseline to week 8 (3.6-5.6 minutes to 16.5-30.7 minutes) in a dose-dependent manner in individuals treated with TAK-861 compared with a decrease in the placebo group from 6.1 minutes at baseline to 4.7 minutes at week 8.
• Least-squares mean differences in the mean change from baseline to week 8 were 13.7 to 26.6 minutes across all TAK-861 doses compared with placebo (adjusted P≤.001).
• 37 to 81% of individuals treated withTAK-861 achieved normal sleep latency (≥20 minutes) at week 8, compared with 5% of individuals in the placebo group.
• For individuals treated with Tak-861, mean ESS scores decreased from baseline to week 8 (18.0-19.0 to 4.8-8.9; the placebo group showed a decrease from 18.6 at baseline to 16.0 at week 8.
• Mean weekly cataplexy rates decreased from baseline to week 8 (15.7-31.1 to 2.1 to 10.1 episodes) in individuals treated with TAK-861 compared with a decrease from 23.1 to 9.0 episodes in the placebo group.

The most common adverse events associated with TAK-861 treatment were insomnia (48% of participants), urinary urgency (33%), and urinary frequency (32%).