ALKS 7290, an investigational OX2R agonist, showed clinically meaningful ADHD symptom improvements in adults in a phase 1 study.
Written By: Saniya Katakdhond, PharmD
Reviewed By: Pharmacally Editorial Team
Alkermes reported positive topline results from a phase 1 proof-of-concept study of ALKS 7290, an investigational oral orexin 2 receptor (OX2R) agonist in development for attention-deficit/hyperactivity disorder (ADHD). In 50 adults with ADHD, 14 days of treatment produced dose-dependent, clinically meaningful improvements in ADHD symptoms and overall disease severity, while ALKS 7290 was generally well tolerated across the tested doses.
The findings represent the first reported clinical evidence of an orexin receptor agonist producing effects on ADHD symptoms, supporting further evaluation of the orexin pathway in ADHD and the dose range selected for an ongoing phase 2 study.
First Clinical Evidence for OX2R Agonism in ADHD
Orexin is a neuropeptide produced in the lateral hypothalamus that regulates wakefulness and engages neural circuits involved in attention, cognition and mood. ALKS 7290 activates the OX2R pathway, providing a mechanistically distinct approach to ADHD treatment. The company is also exploring orexin biology beyond hypersomnolence disorders.
The phase 1 program included 88 healthy volunteers and 50 adults with ADHD. The healthy-volunteer portions evaluated single and multiple ascending doses, while the phase 1b patient study assessed safety, tolerability, pharmacokinetics, pharmacodynamics and exploratory measures of ADHD symptoms.
ALKS 7290 Reduced ADHD Symptom Severity
The phase 1b study was a double-blind, placebo-controlled, parallel-group trial. After a two-week washout of existing ADHD medications, participants received either 20 mg or 50 mg of ALKS 7290 per day in split doses or placebo for 14 days of inpatient treatment. The study was not designed or powered to detect statistically significant differences between treatment groups.
The Adult ADHD Investigator Symptom Rating Scale (AISRS) is a 54-point clinician-administered measure of ADHD symptom severity. Participants entered the study with a median baseline AISRS score of approximately 39, indicating substantial symptom burden.
By day 14, median AISRS scores had decreased from baseline by:
- 14.0 points with 20 mg
- 19.0 points with 50 mg
Clinically meaningful improvements appeared as early as day 6 and extended across both inattentive and hyperactivity/impulsivity subscales.
Improvements Also Seen on Global Disease Severity
ALKS 7290 also improved scores on the Clinical Global Impression-Severity (CGI-S) scale. Median baseline scores were 4.0 in the 20 mg group and 5.0 in the 50 mg group, corresponding to moderately ill and markedly ill severity, respectively.
By day 14, median CGI-S scores had declined by 1.0 point with 20 mg and 2.0 points with 50 mg. The changes represented a shift toward the mildly ill category. Improvements were first observed at day 6.
Because the study was exploratory and not powered for statistical comparisons between treatment groups, these findings should be interpreted as an early clinical signal rather than confirmatory evidence of efficacy.
CNS Activity and Cognitive Findings
The study included EEG-based biomarkers and objective cognitive performance tests to characterize central activity and potential effects on domains relevant to ADHD. ALKS 7290 showed treatment effects across processing speed, information processing, working memory and attention.
These findings also supported dose selection for the ongoing phase 2 study.
Generally, Well Tolerated in Early Development
ALKS 7290 was generally well tolerated across all tested doses in adults with ADHD. No serious treatment-emergent adverse events were reported, and most adverse events were mild.
The most common treatment-emergent adverse events included insomnia, pollakiuria, dizziness, changes in sustained attention, micturition urgency and constipation. No clinically significant findings were reported for hepatic or renal parameters, vital signs or ECGs.
Two participants receiving placebo discontinued the study, while no participants receiving ALKS 7290 discontinued treatment.
In the healthy-volunteer portions of the program, ALKS 7290 was also generally well tolerated, and the maximum tolerated dose was not reached. Pharmacokinetic and pharmacodynamic findings supported oral dosing and continued development.
Phase 2 Study Will Test Efficacy More Rigorously
Alkermes has advanced ALKS 7290 into a phase 2 study (NCT07755410) evaluating once-daily and split-dose regimens against placebo in approximately 312 adults with ADHD.
Participants undergo a two-week washout of existing ADHD medications before randomization to one of three ALKS 7290 dosing regimens or placebo. The primary endpoint is the change from baseline in AISRS total score at week four compared with placebo. The first participant was dosed in September 2026, with data expected in 2027.
The phase 2 trial will determine whether the symptom improvements observed in this short-duration proof-of-concept study can be reproduced in a substantially larger population using a study powered to evaluate comparative efficacy. For ALKS 7290, the results will also provide a more definitive test of whether OX2R agonism can establish a new pharmacologic approach to ADHD treatment.
Reference
Alkermes Announces Positive Phase 1b Results Demonstrating Clinical Proof-of-Concept for ALKS 7290 in Adults with Attention-Deficit Hyperactivity Disorder (ADHD), Alkermes, 21 September 2026
About the Writer
Saniya Sanjay Katakdhond (Linkedin) is a Doctor of Pharmacy professional with hands-on experience in patient case review, clinical documentation, medical record analysis, and patient care.
Her hospital experience has strengthened her understanding of clinical conditions, treatment approaches, and multidisciplinary healthcare practices.
With ICH-GCP certification and a research-oriented approach, she brings clinical insight and attention to detail to healthcare content development.
As a healthcare writer, Saniya focuses on translating clinical knowledge and patient-care experience into clear, accurate, and evidence-informed medical content.