DUBLIN–Alkermes plc (Nasdaq: ALKS) has initiated a Phase 2 clinical trial evaluating its experimental drug ALKS 7290 as an additional treatment for adults with major depressive disorder (MDD), expanding the company’s development program for the investigational therapy.
The study will examine the safety and effectiveness of ALKS 7290 when administered alongside standard antidepressant medications. Researchers will evaluate whether the drug can help reduce depressive symptoms in patients with and without excessive daytime sleepiness.
ALKS 7290 is an oral orexin 2 receptor (OX2R) agonist designed to activate the brain’s orexin system, which plays an important role in regulating wakefulness and is connected to neural pathways involved in attention, cognition and mood.
The experimental treatment is also being developed for attention-deficit hyperactivity disorder (ADHD).
“Orexin biology represents a compelling area of scientific exploration in neuropsychiatry, given its central role in regulating wakefulness and its broad connections to neural circuits relevant to attention, cognition and mood. Through this phase 2, proof-of-concept study, we aim to assess whether activation of the orexin system may offer a novel approach to addressing symptoms of major depressive disorder,” said Craig Hopkinson, M.D. (MBChB), chief medical officer and executive vice president of research and development at Alkermes.
“The initiation of this study marks another important milestone in the rapid advancement of our portfolio of orexin 2 receptor agonists and reflects our commitment to maintaining a leadership position in the development of orexin-based therapies across multiple neuropsychiatric indications.”
The randomized, double-blind, placebo-controlled trial is expected to enroll approximately 180 adults diagnosed with major depressive disorder.
Participants will be randomly assigned to receive either ALKS 7290 or a placebo in combination with their existing antidepressant therapy over a six-week treatment period.
The trial’s primary objective is to assess the safety and tolerability of ALKS 7290. Researchers will also evaluate whether patients receiving the experimental drug experience greater improvements in depressive symptoms than those receiving a placebo.
Treatment effectiveness will be measured using the Montgomery–Åsberg Depression Rating Scale (MADRS) and the Clinical Global Impressions-Severity Scale (CGI-S), with assessments conducted at the sixth week.
The study will include patients who experience excessive daytime sleepiness as well as those who do not, allowing researchers to investigate whether the drug’s effects extend beyond its role in promoting wakefulness.
Orexin is a neuropeptide produced in the hypothalamus that helps regulate the sleep-wake cycle. Its activity also influences neural circuits associated with alertness, cognitive performance and emotional regulation.
By stimulating orexin 2 receptors, ALKS 7290 is being investigated as a potential approach to treating conditions involving impaired attention, cognition and mood.
The drug has previously undergone Phase 1 evaluation in healthy volunteers and adults with ADHD.
Alkermes is currently conducting Phase 2 studies of ALKS 7290 in both ADHD and major depressive disorder, exploring its potential applications across multiple neuropsychiatric conditions.
The newly initiated depression study, registered under clinical trial identifier NCT07901179, represents an early-stage evaluation of whether targeting orexin receptors could provide additional benefits for patients already receiving antidepressant treatment.
ALKS 7290 remains investigational, and its safety and effectiveness for treating major depressive disorder have not yet been established.
