With over 90% of drug candidates failing in clinical trials, largely due to lack of efficacy (~55%) and unacceptable toxicity (~28%), the limitations of traditional animal-based models are increasingly evident. A new review highlights how human-centered new approach methodologies (NAMs) are reshaping the drug discovery landscape.
Title: New approach methodologies for drug discovery
Authors:Wenqiang Liu, Paul D. Pang, Catherine A. Wu, Danilo Tagle, Joseph C. Wu
Published in Cell April 2, 2026
From Animal Models to Human-Relevant Systems
Regulatory shifts are accelerating this transition. The FDA Modernization Act 2.0 (2022) removed the requirement for animal testing in preclinical development, while ongoing initiatives, including the proposed Modernization Act 3.0, aim to integrate AI and real-world data into regulatory science. In parallel, NIH programs such as the Tissue Chip initiative (launched in 2012) and the establishment of a national Organoid Development Center (2025) are supporting the scientific infrastructure for this shift.
Technological Advances Driving Change
NAMs now span the full drug development continuum. Breakthroughs include the development of human embryonic stem cells (1998) and induced pluripotent stem cells (2006–2007), enabling patient-specific disease modeling. Advances in 3D systems, such as organoids (since 2009) and organ-on-chip technologies (since 2010), provide more physiologically relevant models of human tissue.
At the same time, AI-based platforms are transforming drug discovery through predictive modeling, drug repurposing, and toxicity forecasting, significantly reducing time and cost compared with traditional approaches.
Toward Integrated, Human-Centric Pipelines
These technologies are increasingly integrated across the pipeline, from disease modeling to clinical application. NAM-based approaches are already being evaluated in clinical trials across multiple indications, including cancer, neurological, and metabolic diseases. Notably, recent work has demonstrated FDA investigational new drug approval using NAMs-only data, highlighting their growing regulatory acceptance.
Clinical Takeaway
Human-centric NAMs represent a major shift in drug development. By improving prediction of efficacy and safety, these approaches have the potential to reduce failure rates, accelerate translation, and redefine how new therapies are developed and brought to patients.
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Written By Aren Karapetyan, MD