Alkermes reported Phase 1 topline results showing ALKS 7290, an oral orexin 2 receptor agonist, produced dose-dependent reductions in ADHD symptoms in adults. In the Phase 1b arm, median symptom score declines at Day 14 were 14.0 points (20 mg) and 19.0 points (50 mg), with benefits emerging by Day 6. EEG biomarkers and cognitive tests suggested improvements in working memory, attention and processing speed, and no serious treatment-emergent adverse events were reported. Alkermes is now enrolling ~312 adults in a Phase 2 study; larger trials are needed to confirm these early findings.
Alkermes Says Experimental Orexin 2 Agonist ALKS 7290 Shows Early Promise for Adult ADHD
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Alkermes plc on Monday released topline results from a Phase 1 proof-of-concept trial of ALKS 7290, an investigational oral orexin 2 receptor agonist being evaluated as a potential treatment for attention-deficit hyperactivity disorder (ADHD) in adults. The company reports these data represent the first clinical evidence that an orexin receptor agonist can reduce ADHD symptoms.
Study Design and Participants
The study enrolled 88 healthy volunteers and 50 adults diagnosed with ADHD. In the Phase 1b portion, the 50 adults completed a two-week washout of prior ADHD medications and then received 14 days of inpatient treatment with split daily doses of either 20 mg or 50 mg of ALKS 7290, or placebo.
Topline Efficacy Results
At Day 14, ALKS 7290 produced dose-dependent improvements on the Adult ADHD Investigator Symptom Rating Scale. Median reductions from baseline in total symptom scores were 14.0 points in the 20 mg group and 19.0 points in the 50 mg group. Measurable benefit appeared as early as Day 6, with improvements observed across both inattentive and hyperactivity-impulsivity subscales.
The drug also improved overall clinical severity as measured by the Clinical Global Impression–Severity (CGI-S) scale: median CGI-S scores fell by 1.0 point in the 20 mg cohort and by 2.0 points in the 50 mg cohort, shifting median severity ratings from markedly or moderately ill toward mildly ill.
Objective Measures and Cognitive Findings
Electroencephalogram (EEG)–based biomarkers and objective cognitive testing indicated treatment-related effects on domains relevant to ADHD, including working memory, sustained attention, processing speed, and general information processing.
Safety and Tolerability
Safety findings were favorable in this small, short-duration study. Alkermes reported no serious treatment-emergent adverse events related to ALKS 7290. The most commonly reported adverse events were generally mild and included insomnia, pollakiuria (frequent urination), urinary urgency, dizziness, altered sustained attention, and constipation. No participants randomized to ALKS 7290 discontinued the study; two participants in the placebo arm withdrew.
Next Steps and Context
ALKS 7290 targets the orexin pathway, a brain circuit implicated in wakefulness, attention, cognition, and mood. This mechanism differs from current stimulant and nonstimulant ADHD therapies and could represent a novel pharmacologic approach if larger trials confirm these early signals.
Phase 2 Program: Alkermes is enrolling approximately 312 adults with ADHD in a randomized Phase 2 study that will evaluate once-daily and split-dosing regimens over four weeks. Investigators dosed the first participant in September 2026.
Alkermes emphasized these are early topline findings; larger and longer trials will be necessary to confirm efficacy, safety, durability of response, and optimal dosing. Nonetheless, the data provide initial human proof-of-concept that orexin 2 receptor agonism may be a viable new mechanism for treating adult ADHD.
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