Otsuka's Phase 3b Data Show Centanafadine Improves ADHD and Comorbid Anxiety Symptoms Across Clinician and Patient Measures
核心洞察
Otsuka presented Phase 3b results at Psych Congress 2026 showing centanafadine improved ADHD (搜索) and anxiety symptoms in 315 adults with ADHD and comorbid generalized or social anxiety disorder (搜索).
Centanafadine met the primary endpoint with an AISRS treatment difference of -5.87 versus placebo at Week 8, with separation from placebo as early as Week 1.
Pre-specified analyses showed significant gains on self-reported ADHD (搜索) symptoms, executive function, emotional dyscontrol, and clinician- and patient-rated global severity measures.
Otsuka Pharmaceutical Development & Commercialization, Inc. and Otsuka Pharmaceutical Co., Ltd. presented new Phase 3b results for SIMTRIYO (搜索) (centanafadine) in adults with attention-deficit/hyperactivity disorder (ADHD (搜索)) and comorbid anxiety disorders at Psych Congress 2026 in New Orleans. The analyses expand on positive topline results shared in June and cover core ADHD and anxiety symptoms, executive function, emotional dysregulation, and clinician- and patient-reported global assessments.
The findings follow U.S. Food and Drug Administration approval of SIMTRIYO (搜索) for the treatment of ADHD (搜索) 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 stimulant approved by the FDA for ADHD, and it is currently under U.S. Drug Enforcement Administration scheduling review.
Primary and Secondary Endpoint Results
The randomized, double-blind, placebo-controlled Phase 3b study (NCT06973577) enrolled 315 adults aged 18 to 65 with ADHD (搜索) and comorbid generalized anxiety disorder (搜索) (GAD) and/or social anxiety disorder (搜索) (SAD). The primary endpoint was change from baseline in Adult Investigator Symptom Rating Scale (AISRS) total score versus placebo at Week 8, with change from baseline in Hamilton Anxiety Rating Scale (HAM-A) total score as the key secondary endpoint.
At Week 8, centanafadine produced statistically significant and clinically relevant improvements versus placebo on AISRS (LS mean change -18.48 vs -12.62, treatment difference -5.87; p<0.0001), with statistically significant separation from placebo as early as Week 1. On the HAM-A total score, the LS mean change was -12.55 versus -10.63, a treatment difference of -1.92 (p=0.0244).
Self-Reported Symptoms, Executive Function and Emotional Dyscontrol
Three pre-specified additional analyses were presented for the first time. On the Adult ADHD (搜索) Self-Report Scale Expanded Version (ASRS-31), centanafadine showed greater improvement than placebo on the ASRS-18 Total score (LS mean change from baseline -23.10 vs -15.80, treatment difference -7.26; p=0.0002) and on 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). The Executive Function and Emotional Dyscontrol subscales also favored centanafadine (EF: -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.
On the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A), centanafadine improved the Global Executive Composite versus placebo (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, mean changes from baseline were -14.27 versus -10.20, a treatment difference of -4.1 (p=0.0086) at Week 8.
Global Impressions of ADHD and Anxiety Severity
Clinician- and patient-rated global impressions also favored centanafadine. On the clinician-rated CGI-S-ADHD (搜索), LS mean change from baseline was -1.51 versus -1.00, a treatment difference of -0.51 (p=0.0002); on the patient-rated PGI-S-ADHD, the change was -1.80 versus -1.30, a treatment difference of -0.50 (p=0.0033). For anxiety severity at Week 8, the clinician-reported CGI-S-anxiety showed a mean change of -1.51 versus -1.22, a treatment difference of -0.29 (p=0.0261), and the patient-reported PGI-S-anxiety showed -1.65 versus -1.28, a treatment difference of -0.38 (p=0.0267).
"Adults with ADHD (搜索) 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."
Safety and Tolerability
The safety and tolerability profile was generally consistent with the known safety profile for centanafadine and an ADHD (搜索) and anxiety comorbid population. The most common treatment-emergent adverse events (at least 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%).
SIMTRIYO (搜索) carries boxed warnings for suicidal ideation and behaviors in pediatric patients aged 6 years and older, and for abuse, misuse, and addiction. The label also notes contraindications including hypersensitivity to centanafadine or excipients, use with or within 14 days of stopping a monoamine oxidase inhibitor, and pheochromocytoma or a history of pheochromocytoma. Use is not recommended in pediatric patients younger than 6 years or weighing less than 20 kg.
Broader Psychiatric Portfolio
Beyond the Phase 3b analyses, Otsuka presented data spanning its 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 (搜索)/5-HT1A (搜索) agonist with non-D2 activity being studied for the treatment of schizophrenia (搜索). The company said the presentations reflect its continued investment in advancing the science of complex CNS and psychiatric conditions to address unmet needs.
"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 (搜索) to schizophrenia (搜索) 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."
ADHD (搜索) is a chronic neurodevelopmental disorder characterized primarily by impairments in attention, hyperactivity, and impulsivity. According to the Centers for Disease Control and Prevention, it affects approximately 7 million children in the U.S. and an estimated 15.5 million adults. Up to 50% of adults with ADHD have comorbid anxiety disorders, which are associated with higher rates of hospitalization, suicidality, and psychotic symptoms, and many individuals with ADHD and a comorbid anxiety disorder have worse clinical presentation, lower occupational outcomes, and reduced quality of life.