Dublin, Ireland — October 30, 2026
Alkermes plc announced the initiation of a Phase 2 clinical study evaluating ALKS 7290 as an adjunctive treatment for adults with major depressive disorder (MDD). The investigational oral orexin 2 receptor (OX2R) agonist will be studied in combination with standard antidepressant therapy in participants with and without excessive daytime sleepiness. The randomized, double-blind, placebo-controlled trial is expected to enroll approximately 180 adults and will evaluate the candidate’s safety, tolerability and potential effects on depression symptoms. The study expands the clinical development program for ALKS 7290, which is also being investigated for attention-deficit hyperactivity disorder (ADHD). Alkermes is exploring whether activation of the orexin system, which plays a central role in regulating wakefulness and is connected to neural circuits involved in attention, cognition and mood, could provide a new therapeutic approach for people with MDD who require additional treatment alongside antidepressants. The company described the trial as a proof-of-concept study intended to generate early clinical evidence for this approach.
Phase 2 Trial Design and Clinical Objectives
The Phase 2 study will compare ALKS 7290 plus antidepressant therapy (ADT) with placebo plus ADT over a six-week treatment period. Participants will be randomized to receive either the investigational medicine or placebo while continuing antidepressant treatment. The trial’s primary objective is to assess the safety and tolerability of ALKS 7290 when used as an adjunctive therapy in adults with MDD. Its secondary objective is to evaluate whether the combination produces improvements in depression symptom severity compared with placebo plus antidepressant therapy. Symptom changes will be measured from baseline to Week 6 using the Montgomery–Åsberg Depression Rating Scale (MADRS) and the Clinical Global Impressions–Severity Scale (CGI-S). The inclusion of participants with and without excessive daytime sleepiness will allow investigators to assess the candidate in a broader MDD population rather than restricting enrollment to individuals with prominent sleepiness symptoms. The study is registered on ClinicalTrials.gov under identifier NCT07901179. No clinical results have been reported from this newly initiated trial, and its findings will be needed to determine whether ALKS 7290 demonstrates a meaningful signal of activity in adjunctive MDD treatment.
Orexin Biology and ALKS 7290 Development Strategy
ALKS 7290 is an investigational oral agonist of the orexin 2 receptor, designed to activate pathways associated with the neuropeptide orexin. Produced in the lateral hypothalamus, orexin has an important role in maintaining wakefulness and influences neural circuits involved in attention, cognition and mood. Alkermes is investigating whether modulation of this biological system could address symptoms across multiple neuropsychiatric conditions. The candidate has previously been evaluated in a Phase 1 study involving healthy volunteers and adults living with ADHD. It is now being studied in Phase 2 programs for both ADHD and MDD. In the MDD trial, the focus is on its potential as an add-on treatment rather than as a replacement for existing antidepressant medication. The clinical program is part of Alkermes’ broader strategy to develop OX2R agonists for neurological and psychiatric conditions. The company is also advancing investigational orexin-based therapies for other indications, including narcolepsy, idiopathic hypersomnia and fatigue associated with multiple sclerosis and Parkinson’s disease. The extent to which ALKS 7290 may provide clinical benefit across these conditions remains to be established through controlled clinical studies.
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Alkermes’ Neuroscience Pipeline and Next Steps
Alkermes is a global biopharmaceutical company focused on developing medicines for neuroscience-related conditions. Its commercial portfolio includes treatments for alcohol dependence, opioid dependence, schizophrenia, bipolar I disorder and narcolepsy. The company is headquartered in Ireland, with a corporate office and research and development center in Massachusetts and a manufacturing facility in Ohio. The initiation of the ALKS 7290 MDD study adds another indication to its expanding orexin-focused development portfolio. The six-week Phase 2 trial is expected to provide initial information on the candidate’s tolerability and potential effects on depression severity when combined with antidepressants. Results from the study will help inform subsequent development decisions, including whether further clinical evaluation is warranted. As the trial is at an early proof-of-concept stage, the candidate’s efficacy and safety in MDD have not yet been established.
Source:Alkermes, Press release
