Understanding ALKS 2680’s Wake-Promoting Effects Through qEEG: Julia Chapman, PhD

WATCH TIME: 3 minutes

"We saw a decrease in low-frequency drowsiness signals and an increase in high-frequency bands tied to alertness—matching both objective and subjective improvements."

In recent years, the therapeutic landscape for sleep disorders has boomed, with several new, novel options for a variety of different conditions, including emerging pharmacologic treatments. Among the many in development currently includes ALKS 2680 (Alkermes), an oral, once-daily, selective orexin 2 receptor (OX2R) agonist being tested in patients with narcolepsy type 1 and type 2, and idiopathic hypersomnia. Orexin, a growing research topic, is essential in sleep disorders because it regulates wakefulness and arousal, and its deficiency is a key cause of narcolepsy with cataplexy.

At the 2025 SLEEP Annual Meeting, held June 8-11 in Seattle, Washington, a number of posters highlighted the promising early efficacy and safety data behind ALKS 2680. Among them included an exploratory analysis of a phase 1b, randomized, placebo-controlled study testing single doses of the agent (1, 3, and 8 mg for NT1; 5, 12, and 25 mg for NT2 or HI) in a 4-way crossover design. During each Maintenance of Wakefulness Test (MWT) assessment, 3 EEG epochs were extracted for oscillatory and fractal spectral qualitative EEG analysis corresponding to test initiation, sleep onset, and test termination.

Led by Julia Chapman, PhD, findings showed that treatment with the OR2X agonist led to statistically significant wake-promoting effects on several qEEG spectral parameters, which correlated with objective and subjective improvements in wakefulness/alertness. Chapman, a postdoctoral research at the Woolcock Institute of Medical Research, sat down with NeurologyLive® at the meeting to discuss the findings in detail, overviewing specific qEEG parameters that were impacted by ALKS 2680. She spoke on how data from the analysis underscores the agent’s potential wake-promoting effects across a variety of sleep disorders.

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REFERENCE
1. Modi M, Yee B, Chapman J, et al. 0830 Effects of the Orexin 2 Receptor Agonist ALKS 2680 on qEEG in Patients with Narcolepsy and Idiopathic Hypersomnia. Presented at: 2025 SLEEP Annual Meeting; June 8-11; Seattle, WA. ABSTRACT 0830.