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Abstract Details

E2086, a Selective Orexin Receptor Two Agonist: Study for Promoting Wakefulness in Patients With Narcolepsy Type One
Sleep
P6 - Poster Session 6 (5:00 PM-6:00 PM)
14-003

To report results from the first clinical study of E2086, a novel, selective orexin receptor-2 (OX2R) agonist, in patients with narcolepsy type-1 (NT1).
E2086 is hypothesized to regulate the sleep/wake cycle by supporting wakefulness through the orexin neuronal pathway; its preclinical profile showed strong dose-dependent efficacy in promoting wakefulness and mitigating cataplexy. 
E2086-A001-101, a multicenter, randomized, double-blind, double-dummy, single-dose, N-of-1, 5-period crossover study, evaluated the efficacy, safety, and tolerability of E2086 (5 mg, 10 mg, 25 mg) compared with placebo (PBO) and modafinil 200 mg in adult participants with NT1. Male and female participants with verified diagnoses of NT1 were randomized to receive study drug within an hour of waketime following an overnight polysomnogram. Forty-minute maintenance of wakefulness tests (MWTs) were commenced 2 hours after waketime and continued every 2 hours until ~7 hours postdose (4 total). The Karolinska Sleepiness Scale (KSS) was administered at the end of each MWT. 
Twenty-two subjects were randomized; 19 subjects were completers (received all 5 treatments and had MWT efficacy data). Mean sleep latency (MSL) for E2086 was longer and statistically significant compared with PBO and modafinil. MSL with modafinil was also significantly longer versus PBO, establishing assay sensitivity. E2086 10 mg and 25 mg sustained wakefulness for ≥30 minutes; E2086 5 mg sustained wakefulness for >19 minutes throughout each MWT trial. The effect of E2086 on daytime alertness was durable, with participants maintaining significantly greater alertness with E2086 (all doses) versus PBO and with E2086 (10 mg and 25 mg doses) versus modafinil for each KSS assessment. E2086 was generally well tolerated, with most treatment-emergent adverse events being mild to moderate in severity. 
These data demonstrate that E2086 has the potential to improve daytime wakefulness in patients with NT1. The efficacy/safety profile supports continued investigation of E2086 in the narcolepsy patient population. 
Authors/Disclosures
Bruce C. Corser, MD
PRESENTER 		Dr. Corser has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Axsome. Dr. Corser has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Avadel. The institution of Dr. Corser has received research support from Alkermes, . The institution of Dr. Corser has received research support from Apnimed. The institution of Dr. Corser has received research support from Avadel. The institution of Dr. Corser has received research support from Axsome. The institution of Dr. Corser has received research support from Eisai. The institution of Dr. Corser has received research support from Eli Lilly. The institution of Dr. Corser has received research support from Harmony. The institution of Dr. Corser has received research support from Incannex. The institution of Dr. Corser has received research support from Jazz. The institution of Dr. Corser has received research support from Mineralys. The institution of Dr. Corser has received research support from Suven. The institution of Dr. Corser has received research support from Takeda. The institution of Dr. Corser has received research support from Centessa.
Jocelyn Y. Cheng, MD, FAAN (Eisai Inc.) Dr. Cheng has received personal compensation for serving as an employee of Eisai Inc.
james R. Hall, PhD Dr. Hall has nothing to disclose.
Sumit Rawal, PhD Dr. Rawal has received personal compensation for serving as an employee of Eisai.
Margaret Moline Margaret Moline has received personal compensation for serving as an employee of EISAI, INC.. Margaret Moline has received intellectual property interests from a discovery or technology relating to health care. Margaret Moline has received personal compensation in the range of $0-$499 for serving as a review, loan repayment program with NIH.