Alkermes Presents Phase 1b Data on ALKS 2680 Showing Improved Wakefulness in Narcolepsy Type 1 at SLEEP 2024

Alkermes plc has disclosed promising data from a phase 1b study evaluating ALKS 2680, an investigational oral orexin 2 receptor agonist, as a potential once-daily treatment for narcolepsy type 1 (NT1). This data was presented at the 38th annual meeting of the Associated Professional Sleep Societies (SLEEP 2024) in Houston.

The phase 1b study focused on the safety, tolerability, pharmacokinetics, and pharmacodynamics of ALKS 2680, administered once daily. Ten NT1 patients were randomized to receive 1 mg, 3 mg, and 8 mg doses of ALKS 2680 or a placebo, with washout periods between treatments. Initial findings from the first four patients were previously shared at the 2023 World Sleep Congress.

Key findings from the study indicate that ALKS 2680 significantly improved wakefulness compared to placebo at all doses. The Maintenance of Wakefulness Test (MWT) demonstrated a dose-dependent improvement in mean sleep latency. Specifically, mean changes from baseline in sleep latency compared to placebo were 18.4 minutes at 1 mg (p=0.0002), 22.6 minutes at 3 mg (p=0.0001), and 34.0 minutes at 8 mg (p≤0.0001). The placebo group showed a slight decrease in sleep latency by 1.4 minutes. Before treatment, the baseline sleep latency for these patients was about six minutes.

Additionally, at 3 mg and 8 mg doses, the mean MWT scores over an eight-hour post-dose period were within the normal range observed in healthy individuals.

Patient-reported alertness was also assessed using the Karolinska Sleepiness Scale (KSS). This scale ranges from 1 (extremely alert) to 9 (extremely sleepy), with a baseline score of approximately 7 among participants. ALKS 2680 showed a 2 to 3 point improvement in alertness between 1 and 8 hours post-dose, indicating significant enhancement compared to placebo (p<0.001 at all doses).

In terms of safety, ALKS 2680 was well tolerated across all doses. Most adverse events were mild, transient, and resolved without intervention. The most common side effects included insomnia, frequent urination, excess saliva, reduced appetite, dizziness, and nausea. No severe adverse events or clinically significant changes in laboratory values were reported.

Dr. Ron Grunstein, Head of Sleep and Circadian Research at the Woolcock Institute of Medical Research, highlighted the significant treatment effects observed and noted the potential of ALKS 2680 to address unmet needs for individuals with NT1. Dr. Craig Hopkinson, Chief Medical Officer at Alkermes, emphasized the importance of the dose-response data in shaping their ongoing phase 2 study, Vibrance-1, which aims to further evaluate ALKS 2680’s efficacy and safety in NT1 patients.

The phase 1 study also included assessments in healthy volunteers and patients with narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH). This involved single and multiple ascending doses of ALKS 2680, ranging up to 50 mg in healthy participants and up to 25 mg in multiple doses over 10 days.

ALKS 2680 aims to address the pathology underlying narcolepsy by enhancing wakefulness and controlling cataplexy through orexin 2 receptor activation. This investigational drug is currently being further examined in the Vibrance-1 phase 2 study.

Overall, the phase 1b results are encouraging and support the continued clinical development of ALKS 2680 as a potential treatment for NT1.