Alkermes plc presented clinical data from its phase 1b study of ALKS 2680 in patients with narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH) at the European Sleep Research Society's (ESRS) 27th Congress, Sleep Europe 2024. ALKS 2680 is an investigational, oral, selective orexin 2 receptor (OX2R) agonist in development as a once-daily treatment for narcolepsy, a chronic, neurological disorder characterized by excessive daytime sleepiness.
The company shared data from the cohort of patients with NT2 (n=9) from the phase 1b, proof-of-concept study evaluating single-dose, oral administration of ALKS 2680. Additionally, the company presented data from the cohort of patients with IH (n=8) from the same study. ALKS 2680 was generally well tolerated with improved wakefulness compared to placebo in both cohorts.
Phase 1b Study Results
Ron Grunstein, M.D., Ph.D., Head of Sleep and Circadian Research at the Woolcock Institute for Medical Research, stated that the results from the ALKS 2680 phase 1b proof-of-concept study in patients with narcolepsy type 1, narcolepsy type 2 and idiopathic hypersomnia highlight the potential of ALKS 2680 as a treatment option for people living with these sleep disorders, both with and without known orexin deficiency. Treatment with once-daily, oral ALKS 2680 was generally well tolerated with improved wakefulness compared to placebo at all doses tested across all three patient populations, supporting further clinical evaluation.
The phase 1b proof-of-concept part of the study enrolled patients with NT1 (n=10), NT2 (n=9) or IH (n=8). Following an initial two-week washout period of existing medications, patients received single doses of three active dose levels of ALKS 2680 (1 mg, 3 mg and 8 mg for NT1; 5 mg, 12 mg and 25 mg for NT2 and IH) and placebo in a randomized sequence in a four-way crossover design, with washout periods between each treatment in the sequence. The objectives were to assess safety and tolerability, and changes from baseline in average sleep latency, as measured through the Maintenance of Wakefulness Test (MWT) at each crossover period, along with plasma PK, and patient-reported measures of alertness on the Karolinska Sleepiness Scale (KSS).
Ongoing Phase 2 Studies
The company also presented two posters at Sleep Europe 2024 detailing the study design and methods for each of the ongoing phase 2 studies, Vibrance-1 and Vibrance-2, evaluating ALKS 2680 in patients with narcolepsy type 1 and narcolepsy type 2, respectively.
Craig Hopkinson, M.D., Chief Medical Officer and Executive Vice President of Research & Development at Alkermes, stated that they are pleased to share the results from their ALKS 2680 phase 1b, proof-of-concept study in patients with narcolepsy type 2 and idiopathic hypersomnia at Sleep Europe 2024. These data provide further evidence of the clinical profile of ALKS 2680 in patients with sleep disorders and a strong foundation to advance the ALKS 2680 phase 2 program. He also mentioned that they look forward to engaging with clinicians and researchers at this important meeting, sharing the data from their clinical development program, and discussing the design of the ongoing phase 2 studies, Vibrance-1 and Vibrance-2, which are evaluating ALKS 2680 in patients with narcolepsy type 1 and type 2, respectively.
The Vibrance studies are phase 2, randomized, double-blind, dose-range-finding studies evaluating the safety and efficacy of ALKS 2680 compared to placebo in patients with narcolepsy type 1 (Vibrance-1; NCT06358950) and narcolepsy type 2 (Vibrance-2; NCT06555783).
About ALKS 2680
ALKS 2680 is a selective orexin 2 receptor (OX2R) agonist. Orexin, a neuropeptide produced in the lateral hypothalamus, is considered to be the master regulator of wakefulness due to its activation of multiple, downstream wake-promoting pathways that project widely throughout the brain. Targeting the orexin system may address excessive daytime sleepiness across hypersomnolence disorders, whether or not deficient orexin signaling is the underlying cause of disease. Once-daily oral administration of ALKS 2680 was previously evaluated in a phase 1 study in healthy volunteers and patients with NT1, NT2 and IH, and is currently being evaluated in the phase 2 Vibrance-1 and Vibrance-2 studies in patients with NT1 and NT2, respectively.
