Centanafadine Hydrochloride

Centanafadine, an investigational compound for the treatment of ADHD, demonstrated statistically significant improvements vs. placebo for the primary efficacy endpoint in both clinical trials ADHD is one of the most common neurodevelopmental disorders of childhood, with an estimated six million children and adolescents diagnosed in the U.S.1 Otsuka will discuss these results with health authorities TOKYO & PRINCETON, N.J.--(BUSINESS WIRE)-- Otsuka Pharmaceutical Co., Ltd. and its U.S. subsidiary, Otsuka Pharmaceutical Development & Commercialization, Inc., today announced positive results of two, 6-week, Phase 3 clinical trials that evaluated the efficacy, safety, and tolerability of centanafadine for the treatment of adolescents and children with attention-deficit/hyperactivity disorder (ADHD). Centanafadine is a first-in-class norepinephrine, dopamine, and serotonin reuptake inhibitor. The first trial (NCT05257265) was a pivotal Phase 3, randomized, double-blind, three-arm, fixed-dose trial to evaluate the efficacy, safety, and tolerability of centanafadine for adolescents with ADHD from the ages of 13 to 17 years.2 The second trial (NCT05428033) was a pivotal Phase 3, randomized, double-blind, 3-arm, fixed-dose trial to evaluate the efficacy, safety, and tolerability of centanafadine for children with ADHD from the ages of 6 to 12 years.3 The trials were similar in design; both were three-arm, double-blind, fixed-dose trials in which patients were randomized to receive either low-dose centanafadine, high-dose centanafadine, or placebo.2,3 “Otsuka is committed to finding novel solutions for complex, underserved medical needs,” said John Kraus, M.D., Ph.D., executive vice president and chief medical officer, Otsuka Pharmaceutical Development & Commercialization, Inc. “We are pleased these pivotal Phase 3 results demonstrate centanafadine has the potential to offer a new treatment option for children and adolescents who live with ADHD, a condition that can affect every aspect of life.” Topline Results The primary outcome in both trials was the change from baseline to week 6 in the ADHD Rating Scale (ADHD-RS-5) symptoms total score. The first trial (NCT05257265) in adolescents aged 13-17 met its primary endpoint by demonstrating improvements from baseline on the ADHD-RS-5 scale. Patients receiving centanafadine saw statistically significant improvements compared to placebo for both the average effect of the high and low dose ([p=0.0099]) and for the high dose ([p=0.0006]) centanafadine-treated groups. The low-dose centanafadine-treated group did not reach statistical significance. The second trial (NCT05428033) in children aged 6-12 met its primary endpoint by demonstrating improvements from baseline on the ADHD-RS-5 scale. Patients receiving centanafadine saw statistically significant improvements compared to placebo for both the average effect of the high and low dose ([p=0.0039]) and for the high dose ([p=0.0008]) centanafadine-treated group. The low-dose centanafadine-treated group did not reach statistical significance. In both trials, the high dose centanafadine showed separation from placebo as early as week 1, the first post-baseline timepoint, with the effect maintained throughout the study period. In a pooled analysis across the two studies, the most frequently observed side effects for centanafadine (>2 percent and more frequent than placebo) included decreased appetite, nausea, rash, fatigue, upper abdominal pain and somnolence. Overall, the safety and tolerability results were consistent with the pro centanafadine seen within the wider clinical development program. Full study results are not yet available. The trial results are planned to be submitted for scientific publication at a later date. Clinical pharmacology studies and long-term stability studies are underway, and the NDA will be filed in the U.S. as soon as these are completed. Otsuka is incredibly appreciative to all the children and adolescents with ADHD, their families and caregivers, as well as the investigators and site staff who participated in the trial(s) and contributed greatly to this research. About Centanafadine and the Phase 3 Program Centanafadine is a first-in-class norepinephrine, dopamine, and serotonin reuptake inhibitor (NDSRI) being developed for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children, adolescents, and adults. NCT05257265 and NCT05428033 were designed to evaluate the efficacy, safety, and tolerability of centanafadine in adolescents and children with ADHD. The trial populations included male and female patients, aged 13-17 years (inclusive) and 4-12 years (inclusive), respectively, with a primary diagnosis of ADHD based on DSM-5 criteria and confirmed with the MINI-KID. The topline data announced from NCT05428033 is from participants aged 6-17 years. The trial has a separate cohort of children aged 4-5 years that has not yet started.2,3 Both trials consisted of six weeks of double-blind randomized treatment with a 7-day follow-up. Both trials were three-arm, double-blind, fixed-dose trials in which study participants were randomized to receive low-dose centanafadine, high-dose centanafadine, or placebo. The dose for each patient was determined by body weight.2,3 The primary outcome in both trials was the change from baseline to week 6 in the ADHD Rating Scale – ADHD-RS-5 symptoms total score. Trials were conducted in the United States and Canada.2,3 In 2020, Otsuka announced positive topline results from two, six-week, Phase 3 clinical trials that evaluated the efficacy, safety, and tolerability of oral centanafadine for the treatment of adult patients with attention-deficit/hyperactivity disorder. In both studies, centanafadine demonstrated statistically significant improvements vs. placebo for primary and key secondary efficacy endpoints in both studies. Centanafadine was well tolerated in adults, in the combined analysis across the two studies, no adverse event was reported by more than 7 percent of patients.4 About ADHD-RS-5 The Attention-Deficit/Hyperactivity Disorder Rating Scale Version 5 (ADHD-RS-5) is a tool used to evaluate the severity of ADHD symptoms in children and adolescents.5 The scale assessment was conducted by a clinician with the study participant’s caregiver. About Attention-Deficit/Hyperactivity Disorder (ADHD) According to the Attention Deficit Disorder Association, an estimated 9.8 percent (six million) of children and adolescents in the U.S. have attention-deficit/hyperactivity disorder (ADHD).1 ADHD is a neurodevelopmental disorder defined by impairing levels of inattention, disorganization, and/or hyperactivity-impulsivity [DSM-5].1,6 These brain operations include important functions such as attention, concentration, memory, motivation and effort, learning from mistakes, impulsivity, hyperactivity, organization, and social skills. ADHD has no known cure and the majority of people do not outgrow it. Approximately two-thirds or more of children with ADHD continue to have symptoms and challenges in adulthood.7 For additional information on ADHD, please visit the National Institute of Mental Health website. About Otsuka Otsuka Pharmaceutical Co., Ltd. is a global healthcare company with the corporate philosophy: Otsuka–people creating new products for better health worldwide. Otsuka researches, develops, manufactures, and markets innovative products, with a focus on pharmaceutical products to meet unmet medical needs and nutraceutical products for the maintenance of everyday health. In pharmaceuticals, Otsuka is a leader in the challenging areas of mental, renal, and cardiovascular health and has additional research programs in oncology and on several under-addressed diseases including tuberculosis, a significant global public health issue. These commitments illustrate how Otsuka is a “big venture” company at heart, applying a youthful spirit of creativity in everything it does. Otsuka established a presence in the U.S. in 1973 and today its U.S. affiliates include Otsuka Pharmaceutical Development & Commercialization, Inc. (OPDC) and Otsuka America Pharmaceutical, Inc. (OAPI). These two companies’ 2,000 employees in the U.S. develop and commercialize medicines in the areas of mental health and nephrology, using cutting-edge technology to address unmet healthcare needs. OPDC and OAPI are indirect subsidiaries of Otsuka Pharmaceutical Company, Ltd., which is a subsidiary of Otsuka Holdings Co., Ltd. headquartered in Tokyo, Japan. The Otsuka group of companies employed 47,000 people worldwide and had consolidated sales of approximately USD 13.1 billion in 2022. All Otsuka stories start by taking the road less traveled. Learn more about Otsuka in the U.S. at and connect with us on LinkedIn and X at @OtsukaUS. Otsuka Pharmaceutical Co., Ltd.’s global website is accessible at . References Bitsko RH, Claussen AH, Lichstein J, et al. Mental Health Surveillance Among Children - United States, 2013-2019. MMWR Suppl. 2022;71(2):1-42. ClinicalTrials.gov. National Library of Medicine (U.S.). A Trial of Centanafadine Efficacy and Safety in Adolescents With Attention- Deficit/Hyperactivity Disorder. Identifier: NCT05257265. . ClinicalTrials.gov. National Library of Medicine (U.S.). A Trial of Centanafadine Efficacy and Safety in Children With Attention-deficit/ Hyperactivity Disorder (ADHD). Identifier: NCT05428033. . Adler LA, Adams J, Madera-McDonough J, et al. Efficacy, Safety, and Tolerability of Centanafadine Sustained-Release Tablets in Adults With Attention-Deficit/Hyperactivity Disorder: Results of 2 Phase 3, Randomized, Double-blind, Multicenter, Placebo-Controlled Trials. J Clin Psychopharmacol. 2022;42(5):429-439. Markowitz JT, Oberdhan D, Ciesluk A, Rams A, Wigal SB. Review of Clinical Outcome Assessments in Pediatric Attention-Deficit/Hyperactivity Disorder. Neuropsychiatr. Dis Treat. 2020;16:1619-1643. Wolraich ML, Hagan JF Jr, Allan C, et al. Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents [published correction appears in Pediatrics. 2020 Mar;145(3):]. Pediatrics. 2019;144(4):e20192528. Attention deficit Disorder Association. ADHD: The Facts. (n.d.) Available at: (last accessed 24 Oct 2023).

Mark Van Scyoc/Shutterstock The National Institutes of Health (NIH) provides significant funding for drug development research. Across the Pharm Country Hotbed, the agency has provided hundreds of millions of dollars to universities, research institutes and pharmaceutical companies. In 2020, the four top Pharm Country recipients of NIH funding were university systems. These four universities received more than $2 billion in NIH funds. University of Pennsylvania received $593,605,914; University of Pittsburgh received $570,146,095; Columbia University Health Sciences received $558,628,098 in funding; and Yale University received $550,947,887 from the NIH. While universities received the lion’s share of NIH funding in Pharm Country, a number of pharmaceutical companies also secured financial support from the agency. Here’s a look at the Top 10 biopharma companies in Pharm Country that received NIH funding in 2020: Cognition Therapeutics Location: Pittsburgh NIH Funding: $31,493,555 Cognition Therapeutics is a clinical-stage neuroscience company developing drugs that treat neurodegenerative disorders by regulating cellular damage response pathways. Its pipeline compounds target the σ-2 receptor, a key regulator of the cellular damage response. The company’s lead product candidate is CT1812, which is currently in a Phase II study in Alzheimer’s disease. In February, the company published a paper in the Journal of Neuroscience Research evidence that identifies the sigma-2 (σ-2) receptor as integral in the pathology of Parkinson’s disease. The data supports the hypothesis that σ-2 receptor antagonists could represent a unique therapeutic approach to treating some of the underlying disease pathology in Parkinson’s disease and potentially other related diseases like dementia with Lewy bodies, the company said. Venatorx Pharmaceuticals Location: Malvern, PA NIH Funding: $11,323,283 Privately-held Venatorx Pharmaceuticals is focused on improving health outcomes for patients with multi-drug-resistant bacterial infections and hard-to-treat viral infections. The company’s lead developmental product is VNRX-5133 (Cefepime-Taniborbactam), beta-lactamase inhibitor that inhibits both serine- and metallo-beta-lactamases. It is currently in Phase III studies in patients with complicated urinary tract infections (cUTIs). Venatorx believes the asset has the potential to meet unmet medical needs in patients with infections due to carbapenem-resistant pathogens including carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa (CRPA), among others. PsychoGenics Inc. Location: Paramus, NJ NIH funding: $8,428,162 PsychoGenics is a contract research organization with focus on CNS disorders. PsychoGenics provides a full complement of partnered drug discovery capabilities with a focus on psychiatric, cognitive and neurodegenerative disorders, pain, inflammation, spinal cord and traumatic brain injury. The company’s mission is to provide validated disease models and comprehensive preclinical capabilities that help companies develop next-generation treatments for severely disabling CNS and orphan disorders. Theradex Systems, Inc. Location: Princeton, NJ NIH funding: $7,001,002 Founded in 1982 Theradex Systems is a full-service contract research organization that conducts early- to late-stage oncology trials. The company’s mission is to assure that new discoveries in cancer drug development have the very best opportunity to be of benefit to mankind with a vision to improve treatment and make cancer a livable disease. The company conducts oncology trials across the United States, Europe and Asia. Kitware, Inc. Location: Clifton Park, NY NIH funding: $5,161,939 Founded in 1998, Kitware Inc. focuses on the development of innovative open source software platforms and integrating them into research, processes and products. The company provides advanced technical computing, state-of-the-art AI, and full-spectrum software solutions to its partner companies. The company’s core areas of expertise include computer vision, data and analytics, scientific computing, medical computing, and software process. Kitware provides expertise in these areas through customization services, support, collaborative research and development, training, and books. Integral Molecular Location: Philadelphia NIH funding: $4,873,201 Integral Molecular is a research-driven biotechnology company creating innovative technologies and therapeutic antibodies for under-exploited membrane protein targets, including GPCRs, ion channels, transporters and viral envelopes. The membrane proteins are seen as an important group of drug targets found on the surfaces of cells and viruses. The company’s technologies have been integrated into the drug discovery pipelines of over 300 biotech and pharmaceutical companies to help discover new therapies for cancer, diabetes, auto-immune disorders and viral threats such as SARS-CoV-2, Ebola, Zika and dengue virus. Actuated Medical Location: Bellefonte NIH funding: $4,093,577 Actuated Medical was founded in 2006. The company uses electronically controlled motion to develop devices for research and clinical use. Their devices solve unmet clinical needs in target markets, such as gastroenterology, oncology, critical care and pediatrics. Earlier this year, Actuated Medical was accepted as U.S. Small Business Administration 2020 Tibbetts Award Winner. Winners are selected by a panel of judges based on the economic impact of their technological innovation, how they supported federal research and development needs, and their ability to increase commercialization of federal research. Otsuka Pharmaceutical Development & Commercialization, Inc. Location: Princeton, NJ NIH funding: $4,023,155 Otsuka Pharmaceutical Development & Commercialization, Inc., an indirect subsidiary of Japan-based Otsuka Pharmaceutical Co., is dedicated to clinical development of promising drug candidates and services in mental health, oncology, cardio-renal, nephrology and digital health. Other activities include strategic planning for drug approval, marketing, and lifecycle management to maximize a product's full potential. Last year the company announced positive results from Phase III studies of oral centanafadine, a novel investigational compound for the treatment of adult patients with attention-deficit hyperactivity disorder. OLIGOMERIX Location: White Plains, NY NIH funding: $3,406,711 Oligomerix is an emerging biotechnology company focused on developing disease-modifying therapeutics for neurodegenerative diseases characterized by aberrant tau protein ranging from rare tauopathies such as progressive supranuclear palsy and frontotemporal dementia to Alzheimer’s disease. Oligomerix’s lead candidate is a small molecule inhibitor of tau self-association and targets the beginning of the tau aggregation cascade. Other companies have focused on targeting large tau aggregates formed downstream. Last year, the company relocated its headquarters to White Plains to accommodate growth and continue the expansion of research and development operations. Azevan Pharmaceuticals Location: Bethlehem PA NIH funding: $3,190,881 Azevan Pharmaceuticals is a clinical stage, small molecule drug development company developing novel therapeutics to treat stress-related CNS disorders and neurodegenerative conditions. Its clinical compounds are designed to selectively block the effects of arginine vasopressin, a peptide neurohormone involved in the pathophysiology of multiple disorders, including neuropsychiatric symptoms in neurodegenerative diseases, Intermittent Explosive Disorder, and PTSD. The company completed two Phase II clinical trials in adults with its lead compound, SRX246, for the treatment of Intermittent Explosive Disorder and for the treatment of irritability of Huntington’s disease.