Otsuka Submits FDA Application for First-in-Class ADHD Drug Centanafadine
核心洞察
Otsuka Pharmaceutical (搜索) has filed a New Drug Application with the FDA for centanafadine, a first-in-class norepinephrine, dopamine, and serotonin reuptake inhibitor for ADHD (搜索) treatment.
Four pivotal Phase 3 trials demonstrated statistically significant efficacy across children, adolescents, and adults with ADHD (搜索) compared to placebo.
The drug showed a favorable safety profile with low potential for abuse and dependence, potentially expanding treatment options for the 22.5 million Americans with ADHD (搜索).
Otsuka Pharmaceutical Development & Commercialization, Inc. and Otsuka Pharmaceutical (搜索) Co., Ltd. have submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (搜索) for centanafadine, a novel once-daily extended-release treatment for attention-deficit hyperactivity disorder (搜索) (ADHD (搜索)) in children, adolescents, and adults. The submission represents a potential breakthrough in ADHD treatment, as centanafadine is the first investigational norepinephrine, dopamine, and serotonin reuptake inhibitor (NDSRI) to reach this regulatory milestone.
"As an innovator in mental health, we are pleased to take this important step forward in the hope of providing a novel treatment option to patients living with ADHD (搜索)," said John Kraus, M.D., Ph.D., executive vice president and chief medical officer at Otsuka Pharmaceutical Development & Commercialization, Inc. "Centanafadine represents a first in class mechanism of action among available ADHD therapies, and if approved, may expand the range of options available to those managing this complex condition."
Comprehensive Phase 3 Clinical Program
The NDA submission is supported by results from four pivotal Phase 3 clinical trials that evaluated centanafadine's efficacy and safety across different age groups. In all studies, centanafadine demonstrated statistically significant and clinically meaningful improvements in ADHD (搜索) symptoms compared with placebo.
Pediatric Studies Show Promise
The Phase 3 trial in children (NCT05428033) was a randomized, double-blind, three-arm study involving children aged 4 to 12 years with ADHD (搜索). Participants received weight-based high dose, low dose, or placebo for 6 weeks. The primary endpoint measured change from baseline in ADHD Rating Scale-5 (ADHD-RS-5) total score at Week 6. The high-dose group demonstrated statistically significant improvement versus placebo, while the low-dose group did not reach statistical significance.
Similarly, the adolescent trial (NCT05257265) evaluated participants aged 13 to 17 years over a 6-week treatment period. The high-dose group achieved statistically significant and clinically meaningful reductions in ADHD (搜索) symptoms compared with placebo, as measured by the ADHD-RS-5 total score.
Adult Trials Demonstrate Efficacy
Two pivotal Phase 3 trials in adults (NCT03605680, NCT03605836) studied centanafadine sustained-release tablets in adults aged 18 to 55 years with ADHD (搜索). Participants received either centanafadine 200 mg/day, 400 mg/day, or placebo over 6 weeks. The primary endpoint was change from baseline in the Adult ADHD Investigator Symptom Rating Scale (AISRS) total score at Week 6. Both centanafadine dose groups demonstrated statistically significant and clinically meaningful improvements versus placebo.
Safety Profile and Tolerability
Across all studies, centanafadine was generally well tolerated and showed a favorable safety profile with low potential for abuse and dependence. The most common adverse events in children and adolescents included decreased appetite, nausea, rash, fatigue, abdominal pain, and somnolence. In adults, the most frequently reported adverse events were decreased appetite and headache.
In the pediatric trial, the most frequently reported adverse events included decreased appetite, rash, and vomiting. The adolescent study showed similar tolerability, with the most common adverse events being decreased appetite, nausea, headache, and rash.
Addressing Significant Medical Need
ADHD (搜索) is a chronic neurodevelopmental disorder characterized primarily by impairments in attention, hyperactivity, and impulsivity. The condition 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).
Although historically viewed as a childhood disorder, research indicates that many individuals diagnosed with ADHD (搜索) in childhood continue to experience symptoms into adulthood, with some patients experiencing significant impairment. ADHD is often not diagnosed until adulthood, highlighting the need for effective treatment options across all age groups.
First-in-Class Mechanism
Centanafadine's unique mechanism as an NDSRI sets it apart from currently available ADHD (搜索) therapies. Clinical studies have demonstrated that centanafadine significantly reduces core symptoms of ADHD in children, adolescents, and adults, with its novel triple reuptake inhibition potentially offering advantages over existing treatments.
The drug's development represents Otsuka's continued commitment to addressing unmet medical needs in mental health. The company has established itself as a leader in challenging therapeutic areas including mental, kidney, and cardiovascular health, with additional research programs in oncology and under-addressed diseases.