Novel orexin receptor agonist shows potential to improve wakefulness
Eisai has presented new clinical data for its investigational orexin 2 receptor agonist E2086 at the World Sleep 2025 congress in Singapore. The phase 1b trial showed that once-daily dosing may improve daytime wakefulness in people with narcolepsy type 1.
The randomised, double-blind, single-dose, multiple crossover study was conducted in the US and Canada. It compared E2086 with placebo and modafinil in 21 patients meeting criteria for narcolepsy type 1.
Participants received one of five treatments shortly after waking. Efficacy was assessed using the Maintenance of Wakefulness Test (MWT) and the Karolinska Sleepiness Scale (KSS).
All doses of E2086 significantly increased sleep latency compared with placebo (P<0.0001) and modafinil (5 mg: P=0.0009; 10 mg and 25 mg: P<0.0001). KSS scores also showed higher alertness for all doses versus placebo (P<0.0001), with 10 mg and 25 mg outperforming modafinil (P<0.0001).
Treatment-emergent adverse events followed a dose-dependent trend. The most frequent were increased urinary frequency, nausea, dizziness and urinary urgency. No serious adverse events were reported and none led to discontinuation.
Katsutoshi Ido, Chief Scientific Officer at Eisai, said: “At World Sleep 2025, we presented data supporting the potential of E2086 to improve daytime wakefulness in people diagnosed with narcolepsy type 1.”
Eisai has previously developed DAYVIGO, an orexin receptor antagonist for insomnia. E2086, by contrast, activates orexinergic neurons to promote wakefulness. The company aims to expand its contribution to sleep disorder treatment through this new candidate.
Further investigation is planned to confirm E2086’s efficacy and safety in broader narcolepsy populations.