Following Takeda’s historic approval of the first orexin agonist with its narcolepsy treatment Orzeyful, Alkermes has followed up with pioneering data that looks to take the hyped drug class out of sleep disorders and into broader patient populations.
The neuro specialist today shared that its mimic of the brain protein orexin, which regulates arousal and alertness, alleviated symptoms in a small phase 1b trial of 50 adults with attention deficit hyperactivity disorder (ADHD).
Patients were treated with either placebo or ALKS 7290 at 20 mg or 50 mg doses. Following two weeks of treatment, patient scores on the 54-point Adult ADHD Investigator Symptom Rating Scale dropped by an average of 14 and 19 points for the respective dose groups.
On the Clinical Global Impressions Scale of disease severity, a seven-point Likert scale, patients in the 20 mg and 50 mg groups moved from baseline measures of four and five points to average scores of one and two points, according to Alkermes.
“We're the first to move this new class into other diseases,” Alkermes CEO Blair Jackson told Fierce. “We were incredibly happy to see, across a number of different metrics, that the drug performed quite well, and it gives us a lot of things to think about as we design the program moving forward.”
Though the trial was not designed to statistically test ALKS 7290’s efficacy, the first-in-human data “provide early evidence supporting the potential of the orexin pathway to influence the brain’s neural networks that are linked to ADHD,” Greg Mattingly, M.D., a psychiatrist at St. Charles Psychiatric Associates and Washington University School of Medicine, said in Alkermes’ release.
ALKS 7290 produced no new safety signals, Jackson told Fierce, with the most common side effects being dizziness, constipation, change in sustained attention and a more frequent and urgent need to urinate. Frequent urination is a well-known side effect of orexin agonists.
Alkermes is wasting no time moving the drug forward, with a phase 2 trial already enrolling that will test three dosing paradigms across a longer, four-week time span that is more typical of ADHD trials.
Once Alkermes has accrued further safety data in adults, the company plans to launch trials in children as well. ADHD is most common in kids and diagnosis rates have been rising in recent years.
“When you think of these children, ADHD tends to hit them at a very vulnerable stage,” Jackson said. “They lose their confidence, and they're pegged as problem children.”
Diagnosis has been increasing in adults, too, and this massive market makes ALKS 7290 a potential “company changer” for Alkermes, the CEO said, especially when considered in tandem with the biotech’s lead orexin agonist for sleep disorders, alixorexton.
With alixorexton, Alkermes hopes to be the first company to secure approval for an orexin agonist in narcolepsy type 2 and idiopathic hypersomnia, as well as following Takeda’s Orzeyful in narcolepsy type 1.
Another orexin agonist, ALKS 4510, is also in phase 1 development for fatigue that comes with multiple sclerosis and Parkinson's disease. The company's commercial portfolio includes the antipsychotic Aristada for schizophrenia and the central nervous system depressant Lumryz for narcolepsy.
“Alkermes has a bunch of great products for mental health and addiction, and they generate a lot of money for us, but we've never had a blockbuster,” Jackson said. With the widely recognized potential of orexin agonists for sleep disorders and beyond—which some have branded the “GLP-1s of neuroscience,”—that may be about to change.