The European Prevention of Alzheimer's Dementia (EPAD) initiative has begun a novel collaboration between academic and private sectors to test innovative treatments for the prevention of Alzheimer’s dementia.
The EPAD project aims to develop an infrastructure that efficiently enables the undertaking of adaptive, multi-arm, proof-of-concept studies for early and accurate decisions on the ongoing development of drug candidates or drug combinations. This includes evaluating patients' reactions to a drug early in a clinical trial and modifying the trial according to these reactions. The EPAD project will initially run for five years.
The platform will draw European participants, whose records already are part of existing national/regional cohort or register studies, into an EPAD register of approximately 24,000 people. From this group, 6,000 people will be asked to join a pan-European EPAD Cohort for consistent, longitudinal follow-up, and approximately 1,500 of them will eventually be invited to enter the standing EPAD proof-of-concept trial. This approach aims to ensure EPAD has access to an at-risk population showing biomarker evidence of Alzheimer's disease prior to the development of dementia.
All data collected from the cohort and trial will become publically available for analysis to improve disease models in the pre-dementia phase of Alzheimer’s. This should lead to more accurate stratification for trial selection, improved measurements of outcomes and a greater understanding of Alzheimer's processes before dementia develops.
This project has numerous advantages over current approaches. These include excellent pre-trial characterization of subjects to inform selection and reduce screen failure, establishment of the highest possible quality Trial Delivery Centers (TDCs) across Europe, rapid decision making on the likely success of a drug (or combination of drugs) in subsequent confirmatory trials and access to a shared placebo group.
Previous attempts to bring new drugs for Alzheimer’s to the market have been disappointing despite a high level of investment. However, the realization that Alzheimer’s is a progressive disorder and that early intervention may be more effective has led to research efforts being focused on prevention. The goal of the initiative is the prevention of dementia in people with evidence of the disease (such as biomarker abnormalities as identified by specific tests), who still may have little or no complaints or clinical symptoms.
“EPAD is part of a global initiative that will make a fundamental difference to the understanding and management of Alzheimer’s disease in people with very early or no symptoms at all. This could be a game-changer. It is only possible because of the absolute commitment of academics, industry, policy makers and the public to work hand in hand to defeat this global threat,” said Craig Ritchie, EPAD co-coordinator and professor of the psychiatry of aging at the University of Edinburgh.
New tools and methods now allow the identification of patients in the early stages of Alzheimer’s. This creates an opportunity to have new treatment options investigated in clinical studies early on. A difficulty however remains with the large number of patients and study sites needed to confirm a therapeutic effect within a limited span of time. In contrast to several pharmaceutical companies and academic institutions pursuing this in isolation, a joint effort clearly has advantages: the identification and referral of the concerned patients is accelerated and several treatment options can be tested rapidly within one trial.
Therefore, EPAD aims to develop a platform using existing information from national or regional patient cohorts or register studies, which have already identified potential patients. Through EPAD, the undertaking of better, adaptive, multi-arm proof-of-concept studies for early and accurate decisions on the ongoing development of drug candidates or drug combinations is facilitated.
“Preventing the development of dementia in biomarker-positive people would be a fantastic step forward in our fight against Alzheimer’s disease. The EPAD and its novel trial concept will hopefully help speed up the drug discovery progress and bring us closer to this ambitious aim,” said Jean Georges, executive director of Alzheimer Europe.
“This project has numerous advantages over current approaches. These include the excellent pre-trial characterization of subjects to inform selection and reduce screen failure, the establishment of the highest possible quality study sites across Europe, the rapid decision making on the likely success of a drug (or combination of drugs) in subsequent confirmatory trials as well as access to a shared placebo group,” said Serge Van der Geyten, EPAD coordinator and director for neuroscience external affairs at Janssen Pharmaceutica.