TY - JOUR
KW - FDA's new approach methodologies
KW - Drug Discovery
KW - gastrointestinal toxicity
KW - human intestinal organoids
KW - inflammatory bowel disease
AU - Debarun Patra
AU - Ibrahim M. Sayed
AU - Souhrid Mukherjee
AU - Honit Piplani
AU - Aida Habtezion
AU - Michael J. Rosen
AU - Jospeh C. Wu
AB - Reliance on cell lines and animal models for toxicity testing has long been the cornerstone of preclinical drug discovery for intestinal diseases, but the physiology, genetics, and disease etiology of animals differ significantly from those of humans. Species-specific differences contribute to high drug attrition rates at early stages of clinical trial, particularly in complex disorders such as inflammatory bowel disease (IBD), in which such a rate is over 85%. Regulatory shifts by the FDA with the Modernization Act 2.0 and subsequent New Approach Methodologies (NAMs) guidance are accelerating the transition toward human-relevant systems by emphasizing AI-integration, organoid-based assays, and organ-on-chip technologies. Human intestinal organoids (HIOs) have emerged as transformative tools that faithfully replicate the architecture, function, and cellular diversity of the human gut. Advances in the HIOs allow study of drug absorption, metabolism, and toxicity in a dish, providing a bridge between in vitro assays and clinical outcomes to offer new opportunities for improving the prediction of toxicokinetics and pharmacokinetics. Emerging clinical trials employing patient-derived intestinal organoids (PDO) underscore their potential to bridge preclinical and clinical drug development. HIOs, as a disease model, fit well with the FDA's NAMs roadmap, and they will improve drug safety assessment and reduce the use of animal models.
BT - Advanced Science
DO - 10.1002/advs.202522276
IS - n/a
LA - en
N2 - Reliance on cell lines and animal models for toxicity testing has long been the cornerstone of preclinical drug discovery for intestinal diseases, but the physiology, genetics, and disease etiology of animals differ significantly from those of humans. Species-specific differences contribute to high drug attrition rates at early stages of clinical trial, particularly in complex disorders such as inflammatory bowel disease (IBD), in which such a rate is over 85%. Regulatory shifts by the FDA with the Modernization Act 2.0 and subsequent New Approach Methodologies (NAMs) guidance are accelerating the transition toward human-relevant systems by emphasizing AI-integration, organoid-based assays, and organ-on-chip technologies. Human intestinal organoids (HIOs) have emerged as transformative tools that faithfully replicate the architecture, function, and cellular diversity of the human gut. Advances in the HIOs allow study of drug absorption, metabolism, and toxicity in a dish, providing a bridge between in vitro assays and clinical outcomes to offer new opportunities for improving the prediction of toxicokinetics and pharmacokinetics. Emerging clinical trials employing patient-derived intestinal organoids (PDO) underscore their potential to bridge preclinical and clinical drug development. HIOs, as a disease model, fit well with the FDA's NAMs roadmap, and they will improve drug safety assessment and reduce the use of animal models.
EP - e22276
T2 - Advanced Science
TI - Integrating Human Intestinal Organoids into FDA'S New Approach Methodologies for Drug Discovery
UR - https://onlinelibrary.wiley.com/doi/abs/10.1002/advs.202522276
VL - n/a
Y2 - 2026-03-05
SN - 2198-3844
ER -