Otsuka Pharmaceutical Co., Ltd. (Otsuka) and Otsuka Pharmaceutical Development & Commercialization, Inc. (OPDC) announced that the U.S. Food and Drug Administration (FDA) has granted approval of SIMTRIYO^® (centanafadine), a once-daily extended-release capsule for the treatment of attention-deficit hyperactivity disorder (ADHD) in adults and pediatric patients aged 6 years and older weighing at least 20kg on July 24. As the first and only approved norepinephrine, dopamine, serotonin reuptake inhibitor (NDSRI), SIMTRIYO introduces a new treatment approach for patients and healthcare professionals managing this complex and highly individualized condition. By inhibiting the reuptake of norepinephrine, dopamine, and serotonin, SIMTRIYO increases the availability of these neurotransmitters in pathways involved in attention and behavioral regulation. SIMTRIYO, an NDSRI and central nervous system stimulant(CNS), is expected to be available later this year following scheduling by the U.S. Drug Enforcement Administration (DEA).

The approval is supported by results from four pivotal Phase 3 clinical trials evaluating the efficacy and safety of SIMTRIYO across adult, adolescent, and pediatric patients. In these Phase 3 clinical studies, SIMTRIYO demonstrated statistically significant and clinically meaningful improvements in ADHD symptoms compared with placebo, as measured by the ADHD Rating Scale-5 (ADHD-RS-5) in children and adolescents and the Adult ADHD Investigator Symptom Rating Scale (AISRS) in adults. In pediatric and adult studies, improvements in ADHD symptoms were seen as early as week 1. The most common adverse events include decreased appetite, nausea, rash, headache, and abdominal pain in children and adolescents, and headache, decreased appetite, insomnia, nausea, dry mouth, and diarrhea in adults.

"The approval of SIMTRIYO marks an important milestone for people living with ADHD, as it introduces a novel treatment approach for this condition," said John Kraus, M.D., Ph.D., executive vice president and chief medical officer, OPDC. "ADHD is a complex and highly individualized disorder that can affect people throughout childhood, adolescence, and adulthood. Today's approval reflects our commitment to advancing innovative treatment options that address the diverse needs of patients and families managing ADHD. We are deeply grateful to the patients, caregivers, investigators, and clinical teams whose participation made this achievement possible."

Additional clinical research continues to expand the evidence base for centanafadine. In a recently completed Phase 3b study in adults with ADHD and comorbid anxiety, centanafadine demonstrated statistically significant improvements in ADHD symptoms compared with placebo, providing additional insight into its clinical profile. Full study results will be presented at an upcoming scientific meeting.

ADHD is a chronic neurodevelopmental disorder characterized primarily by impairments in attention, hyperactivity, and impulsivity¹. The disorder can affect academic performance, occupational functioning, social relationships, and challenges that impact patients' daily lives¹. Although ADHD is often diagnosed during childhood, symptoms frequently persist into adolescence and adulthood¹.

"ADHD can significantly affect many aspects of daily life across school, work, and relationships," said Dr. Lenard A. Adler, director of the adult ADHD program at NYU Langone Health. "Even when on treatment, because of the heterogenic nature of ADHD, many patients continue to experience symptoms that can interfere with daily functioning. The approval of SIMTRIYO introduces a novel mechanism of action and expands the range of options available to healthcare professionals and patients. Having more therapeutic choices is important because ADHD is a highly individualized condition and treatment decisions should reflect the unique needs of each patient."

Data Supporting Approval

The FDA approval of SIMTRIYO is supported by results from four randomized, double-blind, placebo-controlled Phase 3 clinical trials evaluating the efficacy and safety of centanafadine in children, adolescents, and adults with ADHD.

In the two pivotal adult studies (NCT03605680 and NCT03605836), both centanafadine dose groups demonstrated statistically significant improvements in Adult ADHD Investigator Symptom Rating Scale (AISRS) total scores compared with placebo. Improvements were observed as early as Week 1 and maintained throughout the six-week treatment period. In the pivotal pediatric and adolescent studies (NCT05428033 and NCT05257265), high-dose centanafadine demonstrated statistically significant improvements in ADHD Rating Scale-5 (ADHD-RS-5) total scores compared with placebo. Improvements were observed as early as Week 1.

Across the Phase 3 clinical development program, centanafadine was generally well-tolerated. Clinical and preclinical data demonstrated a well-studied and consistent safety profile. The most common adverse reactions were rash and decreased appetite in children 6 to 12 years of age; decreased appetite, nausea, rash, headache and abdominal pain in adolescents 13 to 17 years of age; and headache, decreased appetite, insomnia, nausea, dry mouth, and diarrhea in adults.

About Attention-Deficit Hyperactivity Disorder (ADHD)

ADHD is a chronic neurodevelopmental disorder characterized primarily by impairments in attention, hyperactivity, and impulsivity¹. It affects approximately 7 million children in the U.S. and an estimated 15.5 million adults, according to the Centers for Disease Control and Prevention (CDC)^2,3.

About SIMTRIYO^® (Centanafadine)

SIMTRIYO^® (centanafadine) is a first-in-class norepinephrine, dopamine, serotonin reuptake inhibitor (NDSRI) and CNS stimulant. Clinical studies have shown that SIMTRIYO significantly reduced symptoms of ADHD in adults and pediatric patients aged 6 years and older weighing at least 20kg. Clinical data suggest SIMTRIYO has demonstrated a well-studied and consistent safety profile.

About Otsuka
Otsuka Pharmaceutical Co., Ltd. is a total healthcare company that focuses on each individual's potential to enhance their well-being. Our medical-related business provides treatments and diagnostics for both physical and mental health. Our nutraceutical business supports daily health maintenance and improvement. Otsuka's unique products and services are based on scientific evidence, under the guidance of our corporate philosophy: Otsuka-people creating new products for better health worldwide.
For further information, please visit www.otsuka.co.jp/en/

• Reference
• 1.American Psychiatric Association (2022). Diagnostic and Statistical Manual of Mental Disorders (5th ed., text rev).
• 2. Staley, Brook S, et al. Attention-Deficit/Hyperactivity Disorder Diagnosis, Treatment, and Telehealth Use in Adults -- National Center for Health Statistics Rapid Surveys System, United States, October-November 2023. US Centers for Disease Control and Prevention.
• 3. Data and Statistics on ADHD. Attention-Deficit/ Hyperactivity Disorder (ADHD). November 19. 2024. U.S. Centers for Disease Control and Prevention. https://www.cdc.gov/adhd/data/index.html