The American Academy of Sleep Medicine and the Sleep Research Society held the 38th annual SLEEP meeting in early June 2024. The meeting allows stakeholders across the sleep sphere to join together to discuss the science and clinical practice behind sleep medicine. During SLEEP 2024, global biopharmaceutical company Alkermes plc presented on the results of a Phase 1b proof-of-concept study seeking to evaluate ALKS 2680 for people with narcolepsy type 1 (formerly known as narcolepsy with cataplexy). More specifically, the trial looked into how safe ALKS 2680 is, how well-tolerated it is, and its pharmacokinetics and pharmacodynamics.

What is ALKS 2680?

ALKS 2680 is an investigational, once-daily orexin 2 receptor agonist. Orexins are a neuropeptide. These neuropeptides play a role in different bodily functions, such as arousal and wakefulness. People with narcolepsy, a chronic neurological disorder that disrupts the sleep-wake cycle, may suddenly fall asleep for a few seconds, a few minutes, or even longer. They can sometimes experience hallucinations when asleep or when waking, as well as sleep paralysis. This is because people with narcolepsy don’t have enough orexin-making neurons, leading to excessive daytime sleepiness (EDS) and, in the case of narcolepsy type 1, cataplexy. Cataplexy is sudden and episodic muscle weakness that often arises from strong emotional responses, such as laughing or crying. This may cause muscle weakness as small as eyelid fluttering or as extensive as entire body weakness, leading to a fall. ALKS 2680 is an agonist, which means it stimulates the body’s orexin system. Ideally, Alkermes hopes that this would resolve underlying symptoms and reduce EDS.

Within the Phase 1b trial, 10 individuals with narcolepsy type 1 were treated either with a placebo or differing ALKS 2680 doses. The study found that:

• ALKS 2680 improved wakefulness and reduced excessive daytime sleepiness in all dose cohorts.
• Individuals taking ALKS 2680 reported heightened alertness.
• ALKS 2680 significantly improved sleep latency. Sleep latency measures how long it takes for you to fall asleep. Individuals with narcolepsy can sometimes experience sleep interruptions or insomnia. ALKS 2680, at the highest dose of 8mg, reduced mean sleep latency by 34 minutes. At the other doses (3mg and 1mg), sleep latency fell by 22.6 minutes and 18.4 minutes respectively.
• This novel therapy was found fairly safe and well-tolerated, regardless of dose. While some individuals experienced side effects such as insomnia, appetite loss, nausea, dizziness, frequent or urgent urination, and salivary overproduction, these side effects were typically mild in nature. No individuals discontinued from the study due to adverse reactions.

Altogether, the results look promising. Alkermes is now advancing ALKS 2680 in the clinical setting. More specifically, Alkermes plans to further evaluate efficacy and safety in the Phase 2 VIBRANCE-1 trial.