ALKS 7290 for Adjunctive Treatment for MDD Enters Phase 2 Study

Alkermes announced the initiation of a phase 2 study evaluating the safety and efficacy of ALKS 7290 as an adjunctive therapy to antidepressants in adults with major depressive disorder (MDD).¹ ALKS 7290 is the company’s investigational orexin 2 receptor (OX2R) agonist, also in development for ADHD.¹

The phase 2 trial is randomized, double-blind, and placebo-controlled, with participants receiving ALKS 7290 or placebo, along with antidepressant therapy, for 6 weeks. The study includes adults with MDD both with and without excessive daytime sleepiness and is expected to enroll approximately 180 participants.

The primary objective is to evaluate the safety and tolerability of ALKS 7290. The secondary objective is to determine whether participants taking ALKS 7290 plus antidepressant therapy show greater improvement in MDD symptom severity than those taking placebo plus antidepressant therapy. Improvement will be measured by change from baseline at week 6 on the Montgomery–Åsberg Depression Rating Scale (MADRS) and the Clinical Global Impressions-Severity Scale (CGI-S).

“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, MD (MBChB), chief medical officer and executive vice president of research and development at Alkermes.¹

ALKS 7290 is a novel, investigational, oral OX2R agonist.¹ Orexin is a neuropeptide produced in the lateral hypothalamus that plays a crucial role in regulating wakefulness and engages multiple downstream pathways and neural circuits relevant to attention, cognition, and mood.¹^,² By targeting the orexin system, the company said, ALKS 7290 has the potential to address symptoms across disorders marked by impairments in these domains.¹ The agent has been evaluated in a phase 1 study in healthy volunteers and adults with ADHD and is also being evaluated in a phase 2 study in adults with ADHD.¹

The company said it is advancing a portfolio of investigational OX2R agonists for narcolepsy, idiopathic hypersomnia, and other psychiatric and neurologic disorders, including ADHD, MDD, and fatigue associated with multiple sclerosis and Parkinson disease.¹

References

1. Alkermes expands ALKS 7290 development program with initiation of phase 2 study for the adjunctive treatment of major depressive disorder (MDD). Press release. October 30, 2026. Accessed October 30, 2026. https://investor.alkermes.com/news-releases/news-release-details/alkermes-expands-alks-7290-development-program-initiation-phase

2. Katzman MA, Katzman MP. Neurobiology of the orexin system and its potential role in the regulation of hedonic tone. Brain Sci. 2022;12(2):150.