Physiopathology

Biomarkers for the Early Stages of Clinical Development in Alzheimer’s Disease

¹ EA 1046, Faculté de Médecine, Université de Lille II, Département Universitaire de Pharmacologie, Lille, France
² ISPED, Inserm U897, Université Victor Segalen Bordeaux 2, Bordeaux, France
³ Fédération des Maladies du Système Nerveux, Hôpital de la Pitié-Salpétrière, Paris, France
⁴ Faculté de Médecine Pierre et Marie Curie, Paris, France
⁵ Innogenetics, Les Ulis, France
⁶ Service de Médecine Nucléaire et Imagerie Fonctionnelle, CHRU Lille, France
⁷ Pôle de Neurologie, Hôpital Salengro, CHRU Lille, France
⁸ GlaxoSmithKline, Marly le Roi, France

Correspondence and offprints : Claude Bidaut-Mazel, GlaxoSmithKline, Direction Médicale, 100 route de Versailles, 78163 Marly le Roi Cedex, France. E-mail: claude.m.bidaut-mazel@gsk.com; claudebidaut-mazel@orange.fr

Received: 4 March 2010
Accepted: 25 May 2010

Abstract

As the failure of several recent Phase III drug development programmes bears witness, the clinical development of “disease-modifying” drugs in Alzheimer’s disease has been confronted with challenging methodological difficulties. Taking into account the financial stakes involved taking drug candidates to the Phase III stage of development, and the risk of investing time and resources fruitlessly in the evaluation of poor candidate drugs, the crucial decision remains whether to proceed from Phase II to Phase III (Go/Nogo). The aim of Phase II studies is to select a molecule likely to be effective in Phase III, but also to eliminate candidate-drugs with an inadequate effect. No consensus currently exists on the best possible design of Phase II studies to inform the Go/Nogo decision optimally. The challenges in choosing the best study design relate to the target population, the end-point criteria used, in particular the use of biomarkers, the experimental protocol, and the study duration. The objective of the Round Table (RT) was to gather the opinions of French experts from the academic, industrial, and regulatory world in order to arrive at a consensus recommendation for the best possible design to be used in Phase II studies in Alzheimer’s disease.