P2‐071: Biomarker Qualification in Alzheimer's Disease

One of the primary challenges for Alzheimer's disease (AD) drug development is understanding disease progression and identifying patients at predementia stages prior to advanced neurodegeneration. At mild-moderate stages of disease, it may be more difficult, and perhaps too late, for treatment to preserve the integrity and functional activity of tissues affected by neurodegenerative disease. Early treatment is emerging as a key clinical approach to current drug development strategies in AD. In addition understanding disease progression remains a critical need in AD drug development. Qualification of patient selection and disease progression models are key enablers for clinical trial studies in AD. As a result, the critical path/coalition against major disease (CAMD) has initiated qualification efforts for early disease selection biomarkers and models for disease progression. Coalition Against Major Disease (CAMD) is made up of scientists from industry, patient advocate groups, academia, and government. It is part of the Critical Path Institute (CPI) funded through Food and Drug Administration and grants. The CAMD teams are focusing upon the qualification of AD disease progression models and upon imaging, biochemical, genetic, and molecular biomarkers. The goal of the CAMD Alzheimer's Disease Biomarkers Workgroup is to deliver a research plan to the FDA and EMA that supports successful qualification of patient selection biomarkers and disease progression models. Two workgroups have submitted qualification packages. The first focuses upon disease progression modeling of ADAS-Cog which is currently under review by both EMA and FDA. The second focuses upon qualification of CSF ABeta42, total tau and MRI based temporal lobe atrophy as tools to enrich an episodically memory impaired, non-demented population at risk of progressing to dementia. Key to the success of both proposals is the importance of data standardization. It is expected that review of the research plan will be an iterative process with periodic input from the regulatory agencies, ultimately resulting in qualification. Qualification guidelines from health agencies have provided a vehicle to better understand the suitability of emerging biomarkers and model simulations as tools to facilitate drug development in AD.