Dr Ron Grunstein Discusses Findings on Investigational Orexin Agonist in Patients With Narcolepsy

Patients who received a novel orexin agonist for narcolepsy type 1 showed encouraging responses, says Ron Grunstein, MD, PhD, head of sleep and circadian research, Woolcock Institute of Medical Research, in Macquarie Park, Australia.

The findings from the ALKS 2680 study were presented at the 2024 SLEEP: American Academy of Sleep Medicine and Sleep Research Society (APSS) Annual Meeting.

This transcript was lightly edited.

Transcript

Can you elaborate on the primary objectives of this study, and the specific safety and pharmacodynamic endpoints you focused on?

This was a phase 1b study, so a first-in-patient study. Previously, there'd been safety studies in healthy volunteers at different doses. This [study] was really to test it in patients with narcolepsy type 1, which is really the most severe form of sleepiness.

Narcolepsy is a pretty disabling condition with severe sleepiness; a clinical feature is called cataplexy, which sometimes involves a lot of other things. But basically, it's a condition where there's a deficiency of orexin, which is a neurotransmitter that basically maintains us awake.

The study really involves testing 3 different doses of an orexin agonist, something that stimulates orexin receptors, which are understimulated in narcolepsy. So, these 3 doses plus placebo were randomly given to 9 patients with narcolepsy type 1. And basically, we found a very efficacious response on that study, which has led to the plan to do a phase 2 study.

What were the inclusion and exclusion criteria for participants in this study, and how did you ensure the selection of a representative sample of patients with narcolepsy?

Well, obviously patients had to be willing to go into the study, which involved a screening period and going off medications, which is an issue for patients. I think we had a reasonably broad sample, both of gender, background, and any comorbidities people had. We sort of called for volunteers through our networks and clinics. The main issue was [that] for most people, they had to provide a bit of time commitment. And so, someone who has a busy job or small children they have to look after, we didn't have those sorts of patients, but otherwise the study went ahead.