Otsuka Presents New Phase 3b Results for SIMTRIYO® (centanafadine) Highlighting Consistent Improvements Across ADHD Symptoms, Anxiety, and Associated Features in Adults with ADHD and Comorbid Anxiety Disorders at Psych Congress 2026

• New Phase 3b results demonstrated consistent improvements with centanafadine across ADHD and anxiety symptoms, executive function and emotional dysregulation, as assessed by both clinicians and patients
• Findings build on SIMTRIYO’s established ADHD clinical program in adults and pediatric patients, expanding its clinical profile in adults with comorbid anxiety disorders
• Data are part of 26 Otsuka-sponsored abstracts at the Congress, reflecting the company’s continued investment in advancing CNS and psychiatric neuroscience research

PRINCETON, N.J. & TOKYO--(BUSINESS WIRE)--Otsuka Pharmaceutical Development & Commercialization, Inc. and Otsuka Pharmaceutical Co., Ltd. (Otsuka) today 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.

INDICATION and IMPORTANT SAFETY INFORMATION for SIMTRIYO^® (centanafadine)

INDICATION
Simtriyo is a norepinephrine-dopamine-serotonin reuptake inhibitor and central nervous system stimulant indicated for the treatment of ADHD in adults and pediatric patients 6 years of age and older weighing at least 20 kg.

Limitations of Use
The use of Simtriyo is not recommended in pediatric patients younger than 6 years of age, because this pediatric subpopulation had a higher incidence of weight loss than pediatric patients 6 years of age and older, or in pediatric patients weighing less than 20 kg, because of a lack of data for this subpopulation and the risk of weight loss.

IMPORTANT SAFETY INFORMATION
WARNING: SUICIDAL IDEATION AND BEHAVIORS IN PEDIATRIC PATIENTS AGED 6 YEARS AND OLDER

Higher rates of suicidal ideation and behaviors occurred in Simtriyo-treated patients aged 6 to 12 years with attention-deficit/hyperactivity disorder (ADHD) than in placebo-treated patients. Closely monitor all pediatric patients for suicidal ideation and behaviors. Consider stopping Simtriyo in patients who experience emergent suicidal ideation and behavior.

WARNING: ABUSE, MISUSE, AND ADDICTION

Simtriyo has a potential for abuse and misuse. Abuse of central nervous system (CNS) stimulants, including Simtriyo, can lead to the development of a substance use disorder, including addiction. Misuse and abuse of CNS stimulants, including Simtriyo, can result in overdose and death. Before prescribing Simtriyo, assess each patient’s risk for abuse, misuse, and addiction. Educate patients and their families about these risks, proper storage of Simtriyo, and proper disposal of any unused drug. Throughout treatment, reassess each patient’s risk and frequently monitor for signs and symptoms of abuse, misuse, and addiction.

Contraindications: Simtriyo is contraindicated in patients with a known hypersensitivity to centanafadine or any of the excipients of Simtriyo, taking or within 14 days of stopping a monoamine oxidase inhibitor, or with pheochromocytoma or a history of pheochromocytoma.

Risks to Patients with Serious Cardiac Disease: Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease.

Increased Blood Pressure and Heart Rate: Assess heart rate and blood pressure following increases in dosage, and periodically while on therapy.

Psychiatric Adverse Reactions: If new psychotic or manic symptoms occur, consider discontinuing Simtriyo.

Hypersensitivity Reactions: Serious hypersensitivity, including anaphylaxis and angioedema, have been reported. If a clinically significant hypersensitivity reaction occurs, immediately discontinue Simtriyo and initiate appropriate therapy.

Long-Term Suppression of Growth in Pediatric Patients: Closely monitor height, body mass index and linear growth in pediatric patients. Consider treatment interruption in patients not growing or gaining height or weight as expected.

Peripheral Vasculopathy Including Raynaud’s Phenomenon: Carefully assess for digital changes during Simtriyo treatment. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for patients who develop signs or symptoms of peripheral vasculopathy.

Serotonin Syndrome: Use of Simtriyo with other serotonergic drugs may cause serotonin syndrome. If occurs, discontinue Simtriyo and/or concomitant serotonergic drug.

Motor and Verbal Tics and Worsening of Tourette’s Syndrome: Regularly monitor patients for the emergence or worsening of tics or Tourette's syndrome. Discontinue Simtriyo if clinically appropriate.

Most commonly observed adverse reactions (≥5% and greater than placebo): The most common adverse reactions in pediatric patients (aged 6 to 12 years) were rash and decreased appetite, and (aged 13 to 17 years) decreased appetite, nausea, rash, headache, and abdominal pain. The most common adverse reactions in adults were headache, decreased appetite, insomnia, nausea, dry mouth, and diarrhea.

Pregnant women exposed to Simtriyo and healthcare providers are encouraged to contact the National Pregnancy Registry for ADHD Medications at 1-866-961-2388 or visiting https://womensmentalhealth.org/research/pregnancyregistry/adhd-medications/

To report SUSPECTED ADVERSE REACTIONS, contact Otsuka America Pharmaceutical, Inc. at 1-800-438-9927 or FDA at 1-800-FDA-1088 (www.fda.gov/medwatch).

Please see FULL PRESCRIBING INFORMATION, including BOXED WARNINGS.

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.  

Otsuka America Pharmaceutical, Inc. and Otsuka Pharmaceutical Development & Commercialization, Inc. are the US-based indirect subsidiaries of the global healthcare company Otsuka Pharmaceutical Co. Ltd. Otsuka’s US companies share a deep commitment to the development and commercialization of innovative products in the spaces of neuroscience, nephrology, and immunology. At our core is perseverance—a fierce determination to overcome any obstacle, regardless of setbacks, on behalf of patients, caregivers, and their loved ones. We will not be bound by doing what’s been done before. Learn more at www.otsuka-us.com.

References

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