FDA accepts centanafadine NDA for priority review for ADHD in children, adolescents

The FDA has accepted for priority review the New Drug Application (NDA) for centanafadine (Otsuka Pharmaceutical), an investigational, once-daily extended-release capsule for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children, adolescents, and adults, according to an announcement from Otsuka Pharmaceutical Development & Commercialization, Inc., and Otsuka Pharmaceutical Co., Ltd. The Prescription Drug User Fee Act (PDUFA) target action date is July 24, 2026.¹

Centanafadine is a first-in-class norepinephrine, dopamine, and serotonin reuptake inhibitor (NDSRI). The NDA is supported by results from 4 pivotal phase 3 clinical trials evaluating efficacy and safety across pediatric, adolescent, and adult populations.¹

“ADHD manifests differently across patients, highlighting the importance of having multiple therapeutic approaches available,” said John Kraus, MD, PhD, executive vice president and chief medical officer, Otsuka Pharmaceutical Development & Commercialization, Inc. “The FDA’s acceptance and priority review designation of our NDA for centanafadine marks an important milestone in our effort to bring forward a novel treatment option for people living with ADHD. If approved, centanafadine would offer a first-in-class NDSRI option designed to support broad symptom management. We extend our sincere gratitude to the patients, caregivers, and investigators whose participation made this milestone possible.”¹

Evidence from pediatric and adolescent phase 3 trials

One phase 3 randomized, double-blind, placebo-controlled trial evaluated centanafadine in children aged 6 to 12 years with a primary diagnosis of ADHD. Participants were randomized to once-daily, weight-based low-dose centanafadine, high-dose centanafadine, or placebo for 6 weeks. The primary endpoint was the change from baseline in total score on the ADHD Rating Scale, version 5 (ADHD-RS-5).²

Among 480 randomized children, high-dose centanafadine demonstrated significantly greater improvement in ADHD-RS-5 total scores compared with placebo at week 6, with separation from placebo observed as early as week 1. Low-dose centanafadine did not meet the primary endpoint. Improvements with high-dose treatment were also observed across inattention and hyperactivity/impulsivity subscales, as well as measures of executive functioning. Treatment-emergent adverse events were generally mild or moderate, with decreased appetite, rash, and vomiting reported most frequently. Both doses were considered safe and well-tolerated over the 6-week treatment period.²

A separate phase 3 randomized, double-blind, placebo-controlled trial evaluated centanafadine in adolescents aged 13 to 17 years. Participants received once-daily centanafadine at fixed doses of 164.4 mg or 328.8 mg, or placebo, for 6 weeks without titration. The primary endpoint was the change from baseline in the ADHD-RS-5 total score at week 6.³

In this trial of 459 adolescents, the 328.8-mg dose demonstrated statistically significant and clinically meaningful improvement in ADHD-RS-5 total scores compared with placebo. Symptom separation from placebo was observed at the first postbaseline assessment and maintained throughout the study period. Improvements were also observed in inattention, hyperactivity/impulsivity, and executive functioning measures. The lower dose did not meet the primary endpoint. Centanafadine was generally well tolerated, with decreased appetite, nausea, headache, and rash reported most commonly. Most adverse events were mild or moderate in severity.³

Clinical context and unmet need

ADHD is a chronic neurodevelopmental disorder characterized by impairments in attention, hyperactivity, and impulsivity. Although often identified in childhood, symptoms frequently persist into adolescence and adulthood, with many patients continuing to experience functional impairment. Pharmacologic treatment remains a cornerstone of ADHD management, yet tolerability concerns, comorbidities, and limited response to existing therapies can restrict long-term use for some patients.

Psychostimulants are commonly prescribed as first-line therapy, but adverse effects such as appetite suppression, sleep disturbance, and concerns regarding misuse may limit suitability for certain individuals. Nonstimulant options are available but may provide less robust symptom control for some patients. Centanafadine’s mechanism of action targets norepinephrine, dopamine, and serotonin reuptake, reflecting growing recognition of serotonin’s role in attention, impulse control, and emotional regulation.

Next steps

According to the press release, if approved, centanafadine would represent a new pharmacologic option for ADHD treatment in children, adolescents, and adults.

Although regulatory review is ongoing, the priority review designation underscores the FDA’s interest in therapies that may address unmet needs in ADHD management across the lifespan.

References

1. Otsuka Pharmaceutical Co LTD. Otsuka Announces FDA Acceptance and Priority Review of New Drug Application for Centanafadine for the Treatment of ADHD in Children, Adolescents, and Adults. Businesswire. January 27, 2026. Accessed January 27, 2026. https://www.businesswire.com/news/home/20260127432877/en/Otsuka-Announces-FDA-Acceptance-and-Priority-Review-of-New-Drug-Application-for-Centanafadine-for-the-Treatment-of-ADHD-in-Children-Adolescents-and-Adults
2. Ward CL, Wilens TE, Jin N, Turkoglu O, Skubiak T, Childress AC. Efficacy and Safety of Centanafadine for ADHD Treatment in Children: A Randomized Clinical Trial. Pediatrics Open Science. 2025;1(3):1-11. doi:https://doi.org/10.1542/pedsos.2024-000349
3. Ward CL, Childress AC, Jin N, Turkoglu O, Skubiak T, Wilens TE. Centanafadine for Attention-Deficit/Hyperactivity Disorder in Adolescents: A Randomized Clinical Trial. Journal of the American Academy of Child & Adolescent Psychiatry. Published online July 4, 2025. doi:https://doi.org/10.1016/j.jaac.2025.06.023