Attention-deficit/hyperactivity disorder (ADHD) is a chronic neurodevelopmental condition marked by inattention, hyperactivity, and impulsive behavior throughout a person’s life. While there are many stimulant and non-stimulant options targeting dopamine and norepinephrine reuptake, centanafadine is a first-in-class norepinephrine, dopamine, and serotonin reuptake inhibitor (NDSRI) developed as a once-daily extended-release oral therapy for ADHD in children, adolescents, and adults. Otsuka’s New Drug Application (NDA) for centanafadine was submitted to the U.S. Food and Drug Administration (FDA) and accepted for priority review after four pivotal phase 3 clinical trials showed strong efficacy, safety, and tolerability.
The NDA submission is supported by data from four pivotal phase 3 clinical trials enrolling pediatric (children and adolescents) and adult ADHD populations. These randomized, double-blind, placebo-controlled studies evaluated the efficacy of centanafadine versus placebo using validated clinician-rated outcome measures—the ADHD Rating Scale-5 (ADHD-RS-5) for children/adolescents and the ADHD Investigator Symptom Rating Scale (AISRS) for adults—and characterized safety and tolerability profiles across age groups. Trial designs included multiple dose arms to explore dose-response relationships, with high-dose centanafadine demonstrating consistent symptom reduction in these controlled settings.
Across the Phase 3 program, centanafadine demonstrated statistically significant and clinically meaningful reductions in core ADHD symptoms compared with placebo in both pediatric and adult cohorts. Symptom improvement was evident on the ADHD-RS-5 and AISRS at primary endpoints, consistent across age ranges. The tolerability profile was generally favorable and consistent with monoaminergic modulation:
- Children/adolescents: most common treatment-emergent adverse events included decreased appetite, nausea, rash, fatigue, abdominal pain, and somnolence.
- Adults: decreased appetite and headache were frequently reported.
Otsuka characterizes centanafadine as having a low potential for abuse, an important consideration in the therapeutic landscape of ADHD treatments.
The FDA’s acceptance of the centanafadine NDA with priority review status reflects the unmet clinical need in ADHD management and the potential importance of a novel mechanism of action that simultaneously targets norepinephrine, dopamine, and serotonin reuptake. If approved, centanafadine would represent the first NDSRI approved for ADHD across pediatric and adult populations, expanding the pharmacologic options available to clinicians and patients. The Phase 3 data underpinning the application indicate clinically meaningful symptom reduction and an acceptable safety/tolerability profile. The decision milestone anticipated by July 24, 2026, will clarify centanafadine’s regulatory and clinical future.