CNS biomarkers: Potential from a regulatory perspective: Case study - Focus in low hippocampus volume as a biomarker measured by MRI.

Our objectives are to describe the procedure for qualification advice and opinion from EU regulators on the use of novel methodologies in drug development, the key stakeholders involved and the evidence requirements for qualification opinion. We present a case study of the request from the Coalition Against Major Disease (CAMD) Consortium of the Critical Path (C-Path) Institute for EU regulators׳ qualification opinion on the use of low hippocampal volume as a biomarker for population enrichment in clinical trials of novel drugs in Alzheimer׳s disease (AD). We discuss the main concerns from the regulators, data analysis requests and guidance during the qualification. EU regulators concluded that low hippocampal volume, measured by vMRI and considered as a dichotomized variable (low volume or not), appears to help enriching recruitment into clinical trials aimed at studying drugs that potentially slow the progression of the pre-dementia stage of AD. The biomarker qualification procedure is a dynamic process in which pharmaceutical companies and research consortia can submit further data to update the qualifications and improve the predictive value of the biomarkers.