Otsuka Pharmaceutical Co., Ltd. (Otsuka) and Otsuka Pharmaceutical Development & Commercialization, Inc. presented new results from the Phase 3b study (NCT06973577) evaluating centanafadine in adults with attention-deficit/hyperactivity disorder (ADHD) and comorbid anxiety disorders at Psych Congress 2026 in New Orleans. Expanding on positive topline results shared in June, these analyses provide the most comprehensive view to date of centanafadine's clinical profile in this clinically complex population, from core ADHD and anxiety symptoms to executive function, emotional dysregulation, and clinician- and patient-reported global assessments. The findings follow the U.S. Food and Drug Administration (FDA) approval of SIMTRIYO^® (centanafadine) for the treatment of ADHD in adults and pediatric patients aged 6 years and older weighing at least 20 kg. SIMTRIYO is the first and only norepinephrine, dopamine, serotonin reuptake inhibitor (NDSRI) and central nervous system (CNS) stimulant approved by the FDA for the treatment of ADHD and is currently under U.S. Drug Enforcement Administration (DEA) scheduling review.

Consistent Improvement with Centanafadine Across Multiple Measures

The expanded Phase 3b dataset includes the study's previously reported primary endpoint, the Adult ADHD Investigator Symptom Rating Scale (AISRS), and key secondary endpoint, the Hamilton Anxiety Rating Scale (HAM-A), together with three additional pre-specified analyses presented for the first time, evaluating multiple dimensions of treatment outcomes.

At Week 8, centanafadine demonstrated statistically significant and clinically relevant improvements compared to placebo on AISRS [LS mean change -18.48 vs -12.62, treatment difference -5.87; p<0.0001], including statistically significant separation from placebo as early as Week 1. Statistically significant improvements versus placebo were also observed in change from baseline in HAM-A total score at Week 8 [LS mean change -12.55 vs -10.63, treatment difference -1.92; p=0.0244].

Three pre-specified additional analyses showed that:

• Adult ADHD Self-Report Scale Expanded Version (ASRS-31): Centanafadine demonstrated greater improvement than placebo across the ASRS-18 Total score (LS mean change from baseline -23.10 vs -15.80, treatment difference -7.26; p =0.0002) and its Hyperactivity/Impulsivity and Inattention subscales (-10.90 vs -7.49, treatment difference -3.42; p=0.0009 and -12.20 vs -8.36, treatment difference -3.8; p=0.0002, respectively), as well as its Executive Function (EF) and Emotional Dyscontrol (ED) subscales (EF: LS mean change from baseline -10.10 vs -7.22, treatment difference -2.89; p<0.0048; ED: -4.00 vs -3.04, treatment difference -0.95; p<0.0484) at Week 8, indicating benefit across both core ADHD symptoms and the associated features that most affect daily functioning.
• Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A): Centanafadine showed greater improvement than placebo on the BRIEF-A Global Executive Composite (LS mean change from baseline at Week 8: -17.73 vs -13.46, treatment difference -4.3; p=0.0126), with statistically significant improvement observed as early as Week 1. On the Behavioral Regulation Index, similar improvement from baseline was also observed, with mean changes from baseline of -14.27 vs -10.20, treatment difference of -4.1; p=0.0086 at Week 8.
• Clinician- and patient-rated global impressions (CGI/PGI): Centanafadine demonstrated greater improvement than placebo across clinician- and patient-rated global severity measures for both ADHD and anxiety, with LS mean change from baseline of -1.51 vs -1.00, treatment difference -0.51; p=0.0002 on the clinician-rated CGI-S-ADHD and -1.80 vs -1.30, treatment difference -0.50; p=0.0033 on the patient-rated PGI-S-ADHD, respectively. A similar pattern was observed in anxiety severity in the centanafadine group vs placebo at Week 8, with mean change from baseline of -1.51 vs -1.22, treatment difference -0.29; p=0.0261 on clinician-reported CGI-S-anxiety, and -1.65 vs -1.28, treatment difference -0.38; p=0.0267 on the patient-reported PGI-S-anxiety, respectively, indicating that treating clinicians and patients themselves independently perceived meaningful improvement.

The safety and tolerability profile was generally consistent with the known safety profile for centanafadine and an ADHD and anxiety comorbid population. The most common treatment-emergent adverse events (≥5 percent and more frequent than placebo) for centanafadine versus placebo were nausea (17.2% vs 5.7%), decreased appetite (13.4% vs 3.2%), and diarrhea (10.2% vs 3.2%).

"Adults with ADHD and comorbid anxiety disorders don't experience their illness as a single symptom scale. Instead, they experience it as attention difficulties, worry, disorganization, and emotional volatility, often all at once," said Corey Hébert, M.D., associate professor at Louisiana State University Health Sciences Center and Tulane University Medical Center. "What's notable about this dataset is that regardless of which lens you use to look at this population, whether a clinician's assessment, a patient's own report, or a measure of day-to-day executive functioning, the findings point in the same direction. That consistency is what clinicians look for when deciding whether a new option is likely to translate into real-world benefit."

"At Otsuka, we're committed to advancing differentiated science that reflects the full complexity of unmet needs across central nervous system conditions and psychiatric illnesses, from ADHD to schizophrenia and beyond," said John Kraus, M.D., Ph.D., executive vice president and chief medical officer, Otsuka. "The breadth of what we're presenting at Psych Congress this year reflects our continued commitment across the range of psychiatric conditions."

Beyond the Phase 3b analyses evaluating centanafadine in adults with ADHD and comorbid anxiety disorders, Otsuka also presented data spanning its broader psychiatric neuroscience portfolio, including data characterizing centanafadine's safety and pharmacokinetic profile and human abuse potential, findings related to aripiprazole and research from the clinical development program for ulotaront, an investigational first-in-class TAAR1/5-HT1A agonist with non-D2 activity being studied for the treatment of schizophrenia. Together, these presentations reflect Otsuka's continued investment in advancing the science of complex CNS and psychiatric conditions to address unmet needs.

About the Phase 3b Study

This randomized, double-blind, placebo-controlled Phase 3b study (NCT06973577) enrolled 315 adults aged 18-65 with ADHD and comorbid generalized anxiety disorder (GAD) and/or social anxiety disorder (SAD). The primary endpoint was change from baseline in Adult Investigator Symptom Rating Scale (AISRS) total score compared to placebo at week 8; key secondary endpoint included change from baseline in Hamilton Anxiety Rating Scale (HAM-A) total score. Other secondary endpoints included measures of additional measures of ADHD and anxiety symptoms and ADHD associated features.

About Attention-Deficit Hyperactivity Disorder (ADHD) and Anxiety

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. Up to 50% of adults with ADHD have comorbid anxiety disorders and are associated with higher rates of hospitalization, suicidality, and psychotic symptoms^4-6. Many individuals with ADHD and a comorbid anxiety disorder have worse clinical presentation, achieve lower occupational outcomes and experience a reduced quality of life^6,7.

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.  

• 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.
• 4. Fu X, Wu W, Wu Y, Liu X, Liang W, Wu R, Li Y. Adult ADHD and comorbid anxiety and depressive disorders: a review of etiology and treatment. Front Psychiatry. 2025 Jun 6;16:1597559. doi: 10.3389/fpsyt.2025.1597559. PMID: 40547117; PMCID: PMC12179154.
• 5. León-Barriera R, Ortegon RS, Chaplin MM, Modesto-Lowe V. Treating ADHD and comorbid anxiety in children: a guide for clinical practice. Clin Pediatr (Phila). 2023;62(1):39-46. doi:10.1177/00099228221111246
• 6. Quenneville AF, Kalogeropoulou E, Nicastro R, Weibel S, Chanut F, Perroud N. Anxiety disorders in adult ADHD: a frequent comorbidity and a risk factor for externalizing problems. Psychiatry Res. 2022;310:114423. doi:10.1016/j.psychres.2022.114423
• 7. Katzman MA, Bilkey TS, Chokka PR, Fallu A, Klassen LJ. Adult ADHD and comorbid disorders: clinical implications of a dimensional approach. BMC Psychiatry. 2017;17(1):302. doi:10.1186/s12888-017-1463-3