FDA Approves Centanafadine for Pediatric and Adult ADHD
Key Clinical Summary:
- The US Food and Drug Administration (FDA) has approved centanafadine (SIMTRIYO), a norepinephrine, dopamine, serotonin reuptake inhibitor (NDSRI), for the treatment of attention-deficit/hyperactivity disorder (ADHD) in adults and pediatric patients aged 6 years and older weighing at least 20 kg.
- Approval was supported by four phase 3 trials demonstrating statistically significant improvements in ADHD symptoms versus placebo, with treatment effects observed as early as week 1 in both adult and pediatric populations.
- Centanafadine is expected to become commercially available later this year following US Drug Enforcement Administration (DEA) scheduling and carries boxed warnings for suicidal ideation and behaviors in pediatric patients and for abuse, misuse, and addiction.
The US FDA has approved centanafadine for the treatment of ADHD, announced manufacturer Otsuka Pharmaceutical Co. The drug is indicated for use in both adults and pediatric patients aged 6 years or older and weighing at least 20 kg.
The once-daily extended-release capsule is the first norepinephrine, dopamine, serotonin reuptake inhibitor (NDSRI) approved for ADHD. It is also classified as a central nervous system (CNS) stimulant.
Regulatory Context
The approval is supported by data from four phase 3 clinical trials, which evaluated the efficacy of centanafadine in pediatric, adolescent, and adult populations.
In 2 adult studies (NCT03605680 and NCT03605836), both centanafadine dose groups achieved statistically significant improvements in Adult ADHD Investigator Symptom Rating Scale (AISRS) total scores versus placebo, with improvements observed as early as week 1 and maintained throughout the 6-week treatment period.
Additional pediatric and adolescent studies (NCT05428033 and NCT05257265) similarly found that high-dose centanafadine demonstrated statistically significant improvements in ADHD Rating Scale-5 (ADHD-RS-5) total scores compared with placebo, with symptom improvement also evident by week 1. Across the phase 3 program, centanafadine was well tolerated.
The most common adverse events in adults included headache, decreased appetite, insomnia, nausea, dry mouth, and diarrhea. In pediatric patients, the most frequently reported adverse events varied by age and included decreased appetite, nausea, headache, abdominal pain, and rash.
The drug also carries boxed warnings regarding suicidal ideation and behaviors in pediatric patients and the potential for abuse, misuse, and addiction.
Clinical Implications
ADHD affects approximately 22.5 million children, adolescents, and adults in the United States and can impair academic, occupational, and social functioning. The approval introduces a new pharmacologic option with a novel mechanism of action, expanding available treatment choices for clinicians.
“Even when on treatment, because of the heterogenic nature of ADHD, many patients continue to experience symptoms that can interfere with daily functioning,” said Lenard A. Adler, MD, director of the adult ADHD program at NYU Langone Health, in a press release. “…Having more therapeutic choices is important because ADHD is a highly individualized condition and treatment decisions should reflect the unique needs of each patient.”
The company expects the drug to become commercially available later this year following scheduling by the US Drug Enforcement Administration (DEA).
