Do Clinical Developments to Date Suggest that Drug Development Based on the Amyloid Hypothesis is Dead?
Chairs: R Anand, L Ereshefsky, D Feltner
Substantial pre-clinical evidence support an amyloid hypothesis as a key causative factor in Alzheimer’s Disease (AD). Genetic studies (knock out animals, population assessments in patients) suggest a link between beta-amyloid deposition in the brain and reduced cognitive capacity. Additionally, the findings from ADNI appear to support a strong association between ‘amyloid’ burden as measured by PET, and significant shifts in CSF A Beta to tau protein ratios with disease progression (prodrome-MCI-Mild/Moderate). Concurrent to ADNI, pharmaceutical companies are developing amyloid-based treatments aimed at slowing or preventing the progression of AD. Recently, the results of several treatment studies targeting amyloid have been reported, demonstrating disappointing results. This session brings together academic, pharmaceutical , and regulatory perspectives to:
- Critically evaluate the validity and robustness of the pre-clinical and genetic models for amyloid in AD (briefly reviewed ), especially focusing on pre-clinical and clinical translational assumptions;
- Describe the experimental medicine models supporting , with high specificity and sensitivity, an amyloid hypothesis for disease progression in AD, i.e., briefly review ADNI and its international counterparts findings. Do these successes predict amyloid targeting drug’s success?
- Identify challenges in drug (small molecules and antibodies ‘targeting amyloid’) methodology, signal detection, and study design aimed at disease course modification and symptomatic claims in AD from recently conducted clinical trials;
- The session will focus on lessons learned and in suggesting improved approaches to evaluate efficacy and/or disease progression across the AD continuum for amyloid modifying therapies.