Coalition Against Major Diseases/European Medicines Agency biomarker qualification of hippocampal volume for enrichment of clinical trials in predementia stages of Alzheimer's disease

Abstract

We summarize the scientific rationale and the data that supported the first qualification of an imaging biomarker by the European Medicines Agency.

Nonlinear cerebral atrophy patterns across the Alzheimer's disease continuum: impact of APOE4 genotype

“…This pattern was observed in most of the regions of the AD brain signature including the hippocampal heads. This finding is in agreement with the hippocampus being considered to be the best established imaging biomarker for the diagnosis of AD (Drago, et al, 2011,Teipel, et al, 2011, Hill, et al, 2014 along with previous findings in APOE4 carriers displaying hippocampal atrophy by the time AD symptoms occur (Wolk and Dickerson, 2010).…”

The Worldwide Alzheimer's Disease Neuroimaging Initiative: An update

“…Amyloid phenotyping for the identification of AD pathology using amyloid PET scans and CSF measurements is now an established approach in observational studies and treatment trials. Hippocampal volume has been approved as a biomarker by the European Medicines Agency, based in part on NA-ADNI data [44]. NA-ADNI's work with multiple imaging modalities has been used to devise required sample sizes for different participant groups in AD trials.…”

AlzheimerÂ’s and ParkinsonÂ’s Diseases Face Common Challenges in Therapeutic Development: Role of the Precompetitive Consortium, Coalition Against Major Diseases

“…The EMA has qualified CSF Aβ and t-tau, and/or amyloid PET imaging for enrichment in AD trials [7] as well as low hippocampal volume (HV) by MRI for enrichment in prodromal AD trials [8]. CAMD represented the consortium that achieved successful EMA qualification of low hippocampal volume for the enrichment of clinical trials in pre-dementia stages of the AD [9]. Qualification of AD biomarkers by FDA is at the consultation and advice stage with an identified key success factor being data sharing of biomarker data from prodromal AD clinical trials.…”