There is an urgent need for new treatments for Alzheimer’s disease. The number of people affected worldwide is expected to reach over 100 million by 2050, yet despite intensive efforts over many years, there is still no cure for Alzheimer’s and little in the way of treatments. Today, research increasingly focuses on ways to prevent the onset of Alzheimer’s in the first place. The EPAD project is pioneering a novel, more flexible approach to clinical trials of drugs designed to prevent Alzheimer’s dementia. Using an ‘adaptive’ trial design should deliver better results faster and at lower cost.
Dementia – focus on prevention
Dementia primarily affects older people, and symptoms include memory loss, confusion, difficulties with communication and everyday tasks, and personality changes. According to the World Health Organization (WHO), an estimated 36 million people globally have dementia, and by 2050 this figure is set to rise to 115 million. A progressive disease that currently has no cure, Alzheimer’s places a huge burden on families, carers and health systems. The total annual costs of Alzheimer’s disease are estimated at around €515 billion, similar to the annual gross domestic product (GDP) of Belgium.
Considerable effort has gone into the search for a cure for Alzheimer’s. However, it is now well known that signs of Alzheimer’s disease can be found in the brain decades before the first symptoms appear. Researchers are therefore increasingly focusing their efforts on finding ways of stopping the disease in its tracks during this pre-symptomatic phase to prevent the disease entirely or at least delay the onset of symptoms.
Challenges here include the difficulty of identifying people who are likely to develop Alzheimer’s dementia, our poor understanding of these earliest stages of the disease, and a lack of flexibility in the way clinical trials are carried out.
The EPAD project is addressing these problems in a number of ways. Firstly, it will draw on existing national and regional registers of people at risk of developing Alzheimer’s dementia to create a single, pan-European EPAD register of around 24 000 people. Of these, the 6 000 deemed to be at greatest risk of Alzheimer’s dementia will be invited to join an EPAD cohort of at risk subjects. This group will undergo standardised tests and follow-up. Finally, the project will select around 1 500 people from this EPAD cohort to take part in early stage ‘adaptive’ clinical trials of drugs designed to prevent Alzheimer’s dementia.
Trialling adaptive trials for Alzheimer’s prevention
In traditional clinical trials, half of the people participating in the trial receive the drug under investigation, and half receive a placebo. Trials may last years and cost a lot of money. In adaptive clinical trials, several candidate drugs are simultaneously compared to each other and to a placebo, meaning that a greater proportion of patients benefit from a potentially active treatment. Furthermore, in an adaptive trial, researchers can adapt the trial design in response to emerging results. For example, if a candidate medicine appears to be particularly effective in only certain groups of people, that medicine can be preferentially given to those people in order to confirm the finding. Similarly, new candidate drugs can be added to the trial and medicines that prove ineffective can be dropped. In addition, adaptive trials allow researchers to test both individual drugs and combinations of different medicines.
This innovative trial design has already proven effective for testing new treatments for breast cancer. The EPAD project is pioneering this approach in Alzheimer’s disease. By adopting this approach, the project expects to be able to identify ineffective medicines earlier in drug development and so avoid failures in more advanced (Phase III) trials. By setting up a cohort of patients ready to enter trials and creating a pan-European network of trial sites, EPAD will also make clinical trials more efficient.
Patients are well represented in the project; this will ensure the project responds to the needs of people with dementia and their families.
The EPAD project does not operate alone. Together with IMI’s EMIF-AD and AETIONOMY projects, it forms the IMI Alzheimer’s disease platform. It is also working closely with other, similar initiatives worldwide, including the US-based Global Alzheimer’s Platform.
In addition, all data collected from the EPAD cohort and trial will be made publicly available for analysis to help researchers everywhere improve their understanding of the early, pre-dementia phase of Alzheimer’s disease.
Ultimately, the hope is that this project will reinvigorate the development of treatments for one of the most challenging diseases facing our ageing societies.