Alkermes Reports Positive Phase 1 Results for Investigational Orexin 2 Receptor Agonist ALKS 7290 in Adult ADHD
Alkermes plc (Nasdaq: ALKS) has announced positive topline results from a Phase 1 proof-of-concept study evaluating ALKS 7290, a novel investigational orexin 2 receptor (OX2R) agonist being developed as a potential treatment for attention-deficit/hyperactivity disorder (ADHD) in adults. The findings provide early clinical evidence supporting the potential of targeting the orexin pathway in ADHD and are being used to inform the ongoing development of ALKS 7290.
The Phase 1 program was designed primarily to assess the safety and tolerability of ALKS 7290, while also examining its pharmacokinetic (PK) and pharmacodynamic (PD) characteristics. The overall program included 88 healthy volunteers and 50 adults diagnosed with ADHD. Across the doses evaluated, ALKS 7290 was generally well tolerated in both populations.
Importantly, adults with ADHD receiving ALKS 7290 showed dose-dependent improvements on exploratory measures of ADHD symptoms. Improvements were observed using the Adult ADHD Investigator Symptom Rating Scale (AISRS) and the Clinical Global Impression-Severity (CGI-S) scale. According to Alkermes, clinically meaningful changes were evident as early as Day 6 and continued through the Day 14 assessment.
The company said the findings represent the first clinical evidence of an orexin receptor agonist producing effects in patients with ADHD. The results also support the dose range selected for the company’s ongoing Phase 2 study, which is evaluating the safety and efficacy of ALKS 7290 in adults with ADHD.
Phase 1b Study Evaluated Adults With ADHD
The Phase 1b portion of the program enrolled 50 adults with ADHD in a double-blind, placebo-controlled, parallel-group study comprising two dosing cohorts. Participants underwent a two-week washout period during which existing ADHD medications were discontinued before treatment began.
Within each cohort, participants were randomized in a 4:1 ratio to receive either ALKS 7290 or placebo. Twenty participants received a total daily dose of 20 mg of ALKS 7290, administered in split doses, while another 20 participants received a total daily dose of 50 mg, also administered in split doses. Ten participants received placebo.
Treatment was administered for 14 days in an inpatient setting. In addition to evaluating safety, tolerability, PK and PD characteristics, investigators assessed several exploratory measures intended to provide an initial understanding of how ALKS 7290 may affect ADHD symptoms.
The study was exploratory in nature and was not designed or statistically powered to establish significant differences between treatment groups. Alkermes said the results are therefore intended to inform further clinical development rather than serve as confirmatory evidence of efficacy.
Improvements in ADHD Symptoms
One of the key assessments was the AISRS, a validated, clinician-administered 54-point scale used to measure the severity of ADHD symptoms. At baseline, participants in the Phase 1b study had a median AISRS total score of approximately 39, reflecting a substantial level of ADHD symptom burden.
Treatment with ALKS 7290 was associated with clinically meaningful reductions in AISRS scores. Improvements were observed as early as Day 6, which was the first post-baseline assessment.
By Day 14, participants receiving the 20 mg daily dose experienced a median 14.0-point reduction from baseline in total AISRS scores. Those receiving the 50 mg dose experienced a median 19.0-point reduction.
The improvements were also observed across the AISRS Inattentive and Hyperactivity/Impulsivity subscales, indicating that the effects were not limited to a single symptom domain.
The second clinical assessment, CGI-S, provided an additional measure of overall ADHD disease severity. Baseline median CGI-S scores were 4.0 in the 20 mg group and 5.0 in the 50 mg group.
As with AISRS, clinically meaningful improvements were reported as early as Day 6. At Day 14, median CGI-S scores had decreased by 1.0 point from baseline in the 20 mg group and by 2.0 points in the 50 mg group.
According to Alkermes, these changes represented a shift in disease severity from moderately or markedly ill toward mildly ill on the CGI-S scale.
Cognitive and Central Nervous System Assessments
The Phase 1b study also incorporated several assessments intended to examine the central activity of ALKS 7290. These included EEG-based biomarkers and performance-based cognitive tests designed to measure brain activity and cognitive domains associated with ADHD symptoms.
The findings provided evidence of treatment-related effects across several cognitive areas, including processing speed, information processing, working memory and attention.
Alkermes said these central nervous system biomarker and cognitive findings helped inform the company’s dose-selection strategy for the ongoing Phase 2 program.
The results are particularly relevant to the company’s development strategy because ALKS 7290 is designed to activate the orexin 2 receptor. Orexin signaling is involved in several functions of the central nervous system, including arousal, alertness and aspects of cognitive function. Alkermes is investigating whether modulation of this pathway can provide a new approach to addressing ADHD symptoms.
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 Washington University School of Medicine, said ADHD can affect multiple areas of a person’s life, including academic performance, professional activities, relationships and physical and emotional well-being.
He noted that the early findings provide evidence supporting further investigation of the orexin pathway in ADHD and suggested that ALKS 7290 could represent a potentially differentiated therapeutic approach if its efficacy and tolerability are confirmed in later-stage studies.
Safety Profile Supports Further Development
Safety and tolerability were key objectives of the Phase 1 program. Alkermes reported that ALKS 7290 was generally well tolerated across all doses tested in adults with ADHD.
No serious treatment-emergent adverse events (TEAEs) were reported among participants with ADHD. Most reported adverse events were mild in severity.
The most frequently reported TEAEs included insomnia, pollakiuria, dizziness, changes in sustained attention, micturition urgency and constipation.
The study did not identify clinically significant findings involving hepatic or renal laboratory parameters, vital signs or electrocardiograms (ECGs). In addition, no participants receiving ALKS 7290 discontinued treatment during the study. Two participants in the placebo group discontinued.
The company also evaluated ALKS 7290 in 88 healthy volunteers through single- and multiple-ascending-dose studies lasting up to 10 days. The drug was generally well tolerated across all doses tested, and a maximum tolerated dose was not reached.
In healthy volunteers, ALKS 7290 demonstrated evidence of central nervous system activity as well as PK and PD characteristics that Alkermes said support oral administration and indicate a wide therapeutic index.
Alkermes Advances Orexin Development Strategy
The positive Phase 1 findings mark an important step in Alkermes’ broader effort to investigate orexin biology outside the area of hypersomnolence disorders.
Craig Hopkinson, M.D. (MBChB), Chief Medical Officer and Executive Vice President of Research & Development at Alkermes, described the Phase 1 study as an important milestone for the company’s orexin portfolio.
According to Hopkinson, the exploratory first-in-patient study was designed to generate early information about the potential of OX2R agonism as a treatment approach for adults with ADHD. The emerging clinical profile of ALKS 7290, he said, provides a foundation for continued investigation of the compound’s safety and efficacy.
The company is now moving forward with a larger Phase 2 clinical study intended to provide more rigorous evidence regarding the potential therapeutic benefit of ALKS 7290.
Phase 2 Trial Now Enrolling
Alkermes’ Phase 2 study is currently enrolling adults with ADHD and is registered under NCT07755410. The trial is evaluating both the safety and efficacy of once-daily and split-dose regimens of ALKS 7290 compared with placebo.
Participants first undergo a two-week washout period for existing ADHD medications before being randomized to one of three ALKS 7290 dosing regimens or placebo.
The Phase 2 study is expected to enroll approximately 312 adults with ADHD. Its primary endpoint is the change from baseline in the AISRS total score at Week 4 compared with placebo.
The first participant in the Phase 2 study was dosed in September 2026.
The larger study will provide an opportunity to evaluate whether the improvements observed in the exploratory Phase 1b study can be replicated in a substantially larger patient population and under a study design specifically intended to assess efficacy.
For Alkermes, the progression into Phase 2 represents the next stage in determining whether OX2R agonism can become a clinically meaningful approach to ADHD treatment. While the Phase 1 findings are preliminary and were not designed to establish statistical efficacy, the observed dose-related changes in ADHD symptom measures, cognitive assessments and central nervous system biomarkers provide the company with clinical data to guide continued development.
As ALKS 7290 advances through Phase 2, the focus will shift toward establishing the consistency, magnitude and durability of its potential effects while continuing to characterize its safety and tolerability profile. The results of the ongoing study will therefore be important in determining the next steps for the investigational therapy and Alkermes’ broader exploration of orexin-based medicines.
About the ALKS 7290 Phase 1 Study
The phase 1 study for ALKS 7290 consisted of three parts: single-ascending dose and multiple-ascending dose evaluations in healthy volunteers (parts 1 and 2), and a phase 1b, proof-of-concept study in adults with attention-deficit hyperactivity disorder (ADHD) (part 3).
In the healthy volunteer portion of the study, each cohort included eight participants, six of whom were randomized to receive ALKS 7290 and two of whom received placebo. In the multiple-ascending dose portion, participants received doses of ALKS 7290 for up to 10 days. The objectives of parts 1 and 2 of the study were to assess ALKS 7290’s safety, tolerability, pharmacokinetics and pharmacodynamics.
The phase 1b proof-of-concept portion of the study (part 3) enrolled 50 adults with ADHD in a double-blind, placebo-controlled, parallel-group study. Following a two-week washout period of existing ADHD medications, participants within each cohort were randomized in a 4:1 (active:placebo) ratio to receive split doses of ALKS 7290 (total daily dose of 20 mg or 50 mg) or matching placebo for 14 days of inpatient treatment. The primary objective was to evaluate the safety and tolerability of ALKS 7290.
Changes from baseline on established clinical ADHD scales, including the ADHD Investigator Symptom Rating Scale (AISRS) and the Clinical Global Impression-Severity Scale (CGI-S), were assessed as an exploratory objective. The study was not designed or powered to detect statistically significant differences between treatment groups; findings disclosed are not in reference to any other study group. The study also included exploratory translational and neuropsychological performance measures to characterize the effects of treatment in a short duration study.
About ALKS 7290
ALKS 7290 is a novel, investigational, oral orexin 2 receptor (OX2R) agonist in development for the treatment of attention-deficit hyperactivity disorder (ADHD). Orexin, a neuropeptide produced in the lateral hypothalamus, plays a crucial role in regulating wakefulness, and engages multiple downstream pathways and neural circuits relevant to attention, cognition and mood.5 By targeting the orexin system, ALKS 7290 has the potential to address symptoms relevant to a broad range of disorders characterized by impairments in these domains. ALKS 7290 has been evaluated in a phase 1 study in healthy volunteers and adults with ADHD, and is currently being evaluated in a phase 2 study in adults with ADHD.
About Alkermes plc
Alkermes plc (Nasdaq: ALKS), a mid-cap growth and value equity, is a global biopharmaceutical company that seeks to develop innovative medicines in the field of neuroscience. The company has a portfolio of proprietary commercial products for the treatment of alcohol dependence, opioid dependence, schizophrenia, bipolar I disorder and narcolepsy.
Alkermes’ pipeline includes late-stage clinical candidates in development for narcolepsy and idiopathic hypersomnia, and orexin 2 receptor agonists in early clinical development for other neurological disorders, including attention-deficit hyperactivity disorder (ADHD) and fatigue associated with multiple sclerosis and Parkinson’s disease. Headquartered in Ireland, Alkermes also has a corporate office and research and development center in Massachusetts and a manufacturing facility in Ohio. For more information, please visit Alkermes’ website at www.alkermes.com.