Abstract Details

Title The Orexin 2 Receptor Agonist ALKS 2680 in Patients with Narcolepsy Type 1: An Initial Proof of Concept Phase 1b Study

Topic Sleep

Presentation(s) P8 - Poster Session 8 (8:00 AM-9:00 AM)

Poster/Presentation
Number 4-004

Objective To present the results from a randomized, double-blind, phase 1b study assessing the safety, tolerability, and pharmacodynamics of ALKS 2680 in patients with narcolepsy type 1 (NT1).

Background ALKS 2680 is a potent, centrally active, orally bioavailable, and highly selective orexin 2 receptor agonist being developed for the once-daily treatment of narcolepsy and idiopathic hypersomnia.

Design/Methods Patients with NT1 received single doses of 1, 3, and 8 mg ALKS 2680 and matching placebo in a 4-way randomized crossover design following 2-week washout of their current narcolepsy treatments. Safety assessments included adverse events (AEs), vital signs, clinical laboratory assessments, and electrocardiograms (ECG). Pharmacodynamic efficacy assessments included the Maintenance of Wakefulness Test (MWT) and the Karolinska Sleepiness Scale (KSS).

Results In patients with NT1 (N=10), there were no serious or severe AEs; no patient discontinued due to any AE. AEs related to study drug and occurring in >1 patient were insomnia, pollakiuria, salivary hypersecretion, decreased appetite, dizziness, and nausea. No drug-related, treatment-emergent, clinically meaningful changes from baseline were identified in laboratory values, vital signs, or ECGs. On the MWT, ALKS 2680 increased mean sleep latency, demonstrating placebo-corrected changes from baseline of 18.4 minutes (1 mg), 22.6 minutes (3 mg), and 34.0 minutes (8 mg) through 8 hours post-dose (p<0.001 for each dose vs placebo). On the KSS, ALKS 2680 showed clinically meaningful, dose-dependent improvements of 2-3 points in self-reported alertness between 1 and 8 hours (p<0.001 for each dose vs placebo).

Conclusions ALKS 2680 was generally well-tolerated. Single doses up to 8 mg led to statistically significant, clinically meaningful improvements in sleep latency and patient-reported alertness and support further clinical evaluation of ALKS 2680 in phase 2.

Authors/Disclosures
Bhaskar Rege PRESENTER	Dr. Rege has received personal compensation for serving as an employee of Alkermes. Dr. Rege has stock in Alkermes. Dr. Rege has received intellectual property interests from a discovery or technology relating to health care.
Ronald R. Grunstein, MBBS, PhD, FRACP	Prof. Grunstein has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli Lilly . Prof. Grunstein has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Apnimed. The institution of Prof. Grunstein has received research support from Alkermes. The institution of Prof. Grunstein has received research support from Eli Lilly.
Brendon Yee, MD, PhD	Prof. Yee has nothing to disclose.
Julia Chapman, PhD	The institution of Dr. Chapman has received research support from American Academy of Sleep Medicine Foundation.
Angela D'Rozario, PhD	The institution of Dr. D'Rozario has received research support from Australian National Health and Medical Research Council. The institution of Dr. D'Rozario has received research support from Australian National Health and Medical Research Council. The institution of Dr. D'Rozario has received research support from Australian National Health and Medical Research Council. The institution of Dr. D'Rozario has received research support from Australian Government Medical Research Future Fund (MRFF) .
Craig Hopkinson, MD	Dr. Hopkinson has received personal compensation for serving as an employee of Alkermes, Inc. An immediate family member of Dr. Hopkinson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for CoRA Consulting LLC. Dr. Hopkinson has received personal compensation in the range of $100,000-$499,999 for serving as an officer or member of the Board of Directors for Alberio. Dr. Hopkinson has stock in Alkermes, Inc.
Jandira Ramos, MPH	Ms. Ramos has received personal compensation for serving as an employee of Alkermes.
Dan G. Smith, PhD	Dr. Smith has received personal compensation for serving as an employee of Alkermes. Dr. Smith has stock in Alkermes.
Sergey Yagoda, MD, PhD	Dr. Yagoda has received personal compensation for serving as an employee of Alkermes, Inc. Dr. Yagoda has stock in Alkermes, Inc.

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