Otsuka reported positive Phase IIIb data for centanafadine in adults with ADHD and comorbid anxiety, extending the clinical evidence supporting the investigational non-stimulant just weeks before the US FDA is due to decide on its New Drug Application. Centanafadine is currently under Priority Review for the treatment of ADHD in children, adolescents, and adults, with a Prescription Drug User Fee Act (PDUFA) target action date of July 24, 2026., strengthening the evidence base for the investigational non-stimulant as it approaches an FDA decision on July 24 under Priority Review. The trial assessed the ability of the triple reuptake inhibitor targeting dopamine, norepinephrine, and serotonin to treat both ADHD and anxiety simultaneously — a clinical problem no currently approved drug addresses with a single label.
The randomized, double-blind, placebo-controlled Phase IIIb study enrolled 315 adults with ADHD and comorbid generalized anxiety disorder and/or social anxiety disorder. Patients receiving centanafadine XR 280 mg once daily achieved statistically significant improvements in ADHD symptoms compared with placebo, meeting the study's primary endpoint. Adult Investigator Symptom Rating Scale (AISRS) total scores improved by a least-squares mean of -18.5 points versus -12.6 points with placebo, a treatment difference of -5.87 points (p<0.0001). Separation from placebo was observed as early as week 1 and was maintained throughout the 8-week study.
The trial also met its key secondary endpoint, demonstrating statistically significant improvements in anxiety symptoms. Hamilton Anxiety Rating Scale (HAM-A) scores improved by a least-squares mean of -12.5 points with centanafadine versus -10.6 points with placebo, corresponding to a treatment difference of -1.92 points (p=0.02). Additional secondary endpoints assessing ADHD-associated features also favored centanafadine.
The findings are clinically relevant because up to half of adults with ADHD have comorbid anxiety disorders, yet no therapy currently carries a US FDA indication for treating both conditions simultaneously. Clinicians often balance stimulant therapies, which may exacerbate anxiety in some patients, against non-stimulants such as atomoxetine and Supernus Pharmaceuticals' Qelbree (viloxazine extended-release), which are approved for ADHD but do not carry anxiety indications. While the current study does not itself establish a regulatory pathway for a combined ADHD-anxiety label, it provides prospective evidence in a population specifically selected for both disorders.
Centanafadine is a first-in-class norepinephrine, dopamine, and serotonin reuptake inhibitor (NDSRI), distinguishing it mechanistically from currently approved non-stimulant ADHD therapies. The Phase IIIb trial was designed to determine whether its broader monoamine profile could improve anxiety symptoms while maintaining efficacy against core ADHD symptoms.
The most frequently reported adverse events occurring in more than 5% of patients and more commonly than placebo included nausea, decreased appetite, diarrhea, insomnia, dry mouth, and vomiting. Otsuka reported that the overall safety and tolerability profile was consistent with previous centanafadine studies and with expectations for patients with ADHD and comorbid anxiety.