Alkermes Shares Topline Results From Phase 1 Proof-of-concept Study Evaluating ALKS 7290 For Attention-deficit Hyperactivity Disorder, Showing Meaningful Improvements In Patients

Alkermes plc (NASDAQ:ALKS) today announced positive topline results from a phase 1 proof-of-concept study evaluating ALKS 7290, the company’s novel, investigational orexin 2 receptor (OX2R) agonist in development for the treatment of attention-deficit hyperactivity disorder (ADHD). The study evaluated the safety and tolerability (primary objective) and pharmacokinetics (PK) and pharmacodynamics (PD) of ALKS 7290 in healthy volunteers (n=88) and in adults with ADHD (n=50). In the phase 1 study, ALKS 7290 was generally well tolerated at all doses tested in healthy volunteers and adults with ADHD. In adult participants with ADHD, ALKS 7290 demonstrated dose-dependent, clinically meaningful improvements on exploratory endpoints evaluating change from baseline on established clinical scales, the Adult ADHD Investigator Symptom Rating Scale (AISRS) and Clinical Global Impression-Severity Scale (CGI-S), at day 14 of treatment. These findings represent the first clinical evidence of the effects of an orexin receptor agonist in the treatment of ADHD and further support the dose range selected for the ongoing phase 2 study evaluating the efficacy and safety of ALKS 7290 in adults with ADHD."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 phase 1b study enrolled 50 adults with ADHD in a double-blind, placebo-controlled, parallel-group trial with two cohorts. Following a two-week washout of existing ADHD medications, participants were randomized (4:1, active:placebo) within each cohort to receive ALKS 7290 (total daily dose of 20 mg (n=20) or 50 mg (n=20), administered in split doses) or placebo (n=10) for 14 days of inpatient treatment. In addition to safety, tolerability and PK and PD effects, the study evaluated change from baseline across a range of exploratory endpoints to begin to characterize the effects of ALKS 7290 on symptoms of ADHD. The study was not designed or powered to detect statistically significant differences between treatment groups.Topline results from the study include:Clinical EndpointsAISRS 1: ALKS 7290 demonstrated clinically meaningful2 improvements from baseline in ADHD symptoms as measured by the AISRS, a 54-point, clinician-administered, validated measure of ADHD symptom severity. At baseline, participants had a median AISRS total score of approximately 39, consistent with substantial ADHD symptom burden. Clinically meaningful improvements were observed as early as day 6, the first post-baseline AISRS assessment. At day 14, treatment with ALKS 7290 demonstrated median reductions from baseline in AISRS total scores of 14.0 points for the 20 mg dose and 19.0 points for the 50 mg dose. Clinically meaningful improvements were observed across AISRS Inattentive and Hyperactivity/Impulsivity subscales.CGI-S 3: ALKS 7290 demonstrated clinically meaningful2 improvements from baseline in overall ADHD disease severity as measured on the CGI-S scale. At baseline, participants had median CGI-S scores of 4.0 and 5.0 in the 20 mg and 50 mg dose groups, respectively. Clinically meaningful improvements were observed as early as day 6, the first post-baseline CGI-S assessment. At day 14, treatment with ALKS 7290 demonstrated median reductions from baseline in CGI-S scores of 1.0 for the 20 mg dose and 2.0 for the 50 mg dose, representing a shift in disease severity from markedly or moderately ill to mildly ill.CNS Biomarkers and Objective Cognitive Performance TestsThe phase 1b study included multiple EEG-based biomarkers and performance-based cognitive tests designed to measure dose-related central activity and domains underlying ADHD symptoms. Findings from these assessments support our dosing decisions for phase 2 and showed treatment effects of ALKS 7290 across important cognitive domains, including processing speed, information processing, working memory and attention.Topline SafetyALKS 7290 was generally well tolerated across all doses tested in participants with ADHD. No serious treatment-emergent adverse events (TEAEs) were reported.Most TEAEs were mild in severity. The most common TEAEs4 were insomnia, pollakiuria, dizziness, change in sustained attention, micturition urgency, and constipation.There were no clinically significant findings observed in hepatic or renal parameters, vital signs or ECGs.Two participants in the placebo group discontinued the study; there were no discontinuations among participants receiving ALKS 7290.In healthy volunteers (n=88), single- and multiple-ascending doses of ALKS 7290 were evaluated for up to 10 days. ALKS 7290 was generally well tolerated across all doses tested and the maximum tolerated dose was not reached. ALKS 7290 was observed to be centrally active and to have a PK and PD profile that supports oral dosing with a wide therapeutic index."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 evaluating the safety and efficacy of once-daily and split doses of ALKS 7290 compared to placebo in adults with ADHD is currently enrolling (NCT07755410). Following a two-week washout period of existing ADHD medications, participants will be randomized to receive one of three dosing regimens of ALKS 7290 or placebo. The study will evaluate the primary endpoint of change from baseline in AISRS total score at week four compared to placebo. The study is expected to enroll approximately 312 participants with ADHD. The first participant was dosed in September 2026.