Pharmacometrics for the Win: How Modeling Helps Demonstrate Efficacy in Alzheimer’s Disease and Provides Insight into Drug Activity

This presentation will describe how “traditional” pharmacometrics models are being used in drug development for Alzheimer’s disease. Early trials in AD were hampered by poor safety profiles or dose selection strategies that ultimately failed to provide insight into the processes that drive Alzheimer’s disease. With increased use of pharmacometrics to drive dose selection along with improvements in available biomarkers, current AD trials are able to effectively test whether a mechanism of action impacts disease progression. Furthermore, these models can be used to provide supportive evidence of efficacy and safety to aid in regulatory decisions. Examples of how exposure-response models of both plasma biomarkers and clinical outcomes were used to support approval of lecanemab will be provided. Finally, a new model linking change in amyloid PET with change in clinical outcomes (CDR-SB) will be shared, demonstrating how these models provide additional insight into drug activity and can help identify patient characteristics that influence clinical outcome.