P111: Regulatory and Developmental Trends in ADHD Drug Development: Lessons from Centanafadine and Gaps in Female Representation
Poster Presenter
Ellie Froslan
Student
University of Southern California United States
Objectives
ADHD is often treated with stimulant medications that carry abuse and safety concerns, especially in children. This analysis examines evolving regulatory and clinical trial standards in ADHD drug development using centanafadine, emphasizing safety, innovation, and sex-based representation gaps.
Method
A comparative regulatory analysis used FDA guidance documents, PubMed, ClinicalTrials.gov records, and Phase 1–3 trial data to examine evolving standards in ADHD drug development, using centanafadine as a case study with emphasis on safety, innovation, and gaps in sex-based representation.
Results
Historically, ADHD medications were approved based on relatively short-duration trials with smaller sample sizes and limited demographic diversity, with females often underrepresented. In contrast, modern regulatory expectations require larger, longer, and more inclusive trials, along with pediatric study plans, abuse-liability assessments, and extended safety monitoring. Centanafadine, a triple monoamine reuptake inhibitor targeting dopamine, norepinephrine, and serotonin, exemplifies this regulatory shift. Across Phase 1–3 trials, more than 1,500 participants were enrolled, including substantial female representation. In pooled adult Phase 3 studies (~900 patients), approximately 48–52% of participants were women, representing an improvement compared with historical ADHD trials. Centanafadine met primary efficacy endpoints in both adult and pediatric populations, demonstrating statistically significant symptom reduction versus placebo, early separation by Week 1, and a generally favorable tolerability profile with mostly mild adverse events. Pediatric and adolescent trials also met regulatory efficacy requirements, supporting development across age groups; however, female representation remained somewhat lower in younger cohorts.
Conclusion
ADHD drug development has transitioned toward higher regulatory rigor, broader safety evaluation, and improved demographic inclusion. Centanafadine’s clinical program reflects these advances and highlights progress in addressing historical underrepresentation of women in ADHD research. However, persistent gaps remain, particularly in early-life studies and sex-stratified analyses. Future ADHD drug development should prioritize inclusive trial designs, long-term safety assessment, and regulatory strategies that ensure therapies are evaluated in populations reflective of real-world patients. These efforts are essential to advancing equitable, evidence-based ADHD care.
