Dublin — Alkermes plc announced positive topline results from a Phase 1b proof-of-concept study of ALKS 7290, an investigational orexin 2 receptor agonist being developed to treat attention-deficit hyperactivity disorder in adults.
The study evaluated the safety, tolerability, pharmacokinetics and pharmacodynamics of ALKS 7290 in 88 healthy volunteers and 50 adults with ADHD. The company said the drug was generally well tolerated at all doses tested.
Among adults with ADHD, ALKS 7290 produced dose-dependent improvements after 14 days on exploratory measures of ADHD symptoms, including the Adult ADHD Investigator Symptom Rating Scale, or AISRS, and Clinical Global Impression-Severity Scale, or CGI-S.
Alkermes said the results provide the first clinical evidence of an orexin receptor agonist being used to treat ADHD and support the dose range selected for an ongoing Phase 2 study.
“ADHD is a common mental health condition that can have profound effects on multiple aspects of daily life, including academic achievement, career success, relationships and overall physical and emotional well-being. For many patients today, there remains a critical need for differentiated therapies that provide strong, well-tolerated efficacy,” said Greg Mattingly, M.D., Founding Partner of St. Charles Psychiatric Associates, President at Midwest Research Group and Associate Clinical Professor in the Department of Psychiatry at the Washington University School of Medicine.
“These data provide early evidence supporting the potential of the orexin pathway to influence the brain’s neural networks that are linked to ADHD and suggest that ALKS 7290 could represent a meaningful new therapeutic approach for patients.”
The double-blind, placebo-controlled Phase 1b study enrolled 50 adults with ADHD in two cohorts. Following a two-week washout of existing ADHD medications, participants were randomized to receive ALKS 7290 at a total daily dose of either 20 mg or 50 mg, administered in split doses, or placebo for 14 days.
The study was designed primarily to assess safety, tolerability and pharmacokinetic and pharmacodynamic effects and was not powered to detect statistically significant differences between treatment groups.
Participants had a median AISRS score of about 39 at baseline. By day 14, median scores had fallen by 14 points among participants receiving the 20 mg dose and by 19 points among those receiving the 50 mg dose. Improvements were also observed in inattentive and hyperactivity/impulsivity measures.
On the CGI-S scale, median scores declined by one point in the 20 mg group and two points in the 50 mg group by day 14.
The study also included EEG-based biomarkers and cognitive performance tests. Alkermes said the results showed treatment effects across areas including processing speed, information processing, working memory and attention.
No serious treatment-emergent adverse events were reported among participants receiving ALKS 7290, and most adverse events were mild. The most commonly reported events included insomnia, frequent urination, dizziness, changes in sustained attention, urinary urgency and constipation.
The company said no clinically significant changes were observed in liver or kidney parameters, vital signs or electrocardiograms. Two participants receiving placebo discontinued the study, while there were no discontinuations among participants receiving ALKS 7290.
In the healthy-volunteer portion of the program, 88 participants received single and multiple ascending doses for up to 10 days. Alkermes said the maximum tolerated dose was not reached.
“Results from this phase 1 study of ALKS 7290 represent an important milestone in the advancement of our orexin portfolio and support our strategy to explore the potential of orexin biology beyond hypersomnolence disorders,” said Craig Hopkinson, M.D. (MBChB), Chief Medical Officer and Executive Vice President of Research & Development at Alkermes.
“This exploratory, first-in-patient study was designed to provide early insights into the potential of orexin 2 receptor agonism as a novel treatment for adults with ADHD, and we are excited to see the emerging clinical profile of ALKS 7290. The results begin to build the foundation of our understanding of ALKS 7290, and we look forward to further evaluating its safety and efficacy in our ongoing well-powered phase 2 study.”
A Phase 2 study of ALKS 7290 is currently enrolling adults with ADHD and is expected to include approximately 312 participants. The trial will compare three dosing regimens with placebo and evaluate changes in AISRS scores after four weeks. The first participant was dosed in September 2026, and Alkermes expects study data in 2027.
