Clinical Trials in Alzheimer’s disease Conference 2015

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Clinical Trials in Alzheimer’s disease Conference 2015


This year the Clinical Trials in Alzheimer ’s disease (CTAD) conference was held in Barcelona from Nov 5th to 7th. We sent someone along from our Research team to get up to speed with global progress in the development of new treatments for Alzheimer’s disease.

Most of the research presented focused on the search for treatments that can slow down the progression of the disease. But there were also some studies looking to improve treatments to help people to manage some of the symptoms, such as agitation and aggression, that can help people with dementia and their families live better with the condition.

In the search to identify the first disease modifying treatment, research efforts are moving to test treatments is the earliest stages of Alzheimer’s disease. Most current trials are testing drugs in people who only have mild memory impairments (sometimes referred to as prodromal Alzheimer’s disease) or even earlier in the preclinical stages before any dementia symptoms can be detected.




Getting the negatives out of the way


Day one of CTAD 2015 started with discussion of a number of failed or negative trial results. Some of these we knew were coming, such as the Scarlet RoAD trial of an antibody treatment called gantenerumab which was terminated last December after an interim analysis found it was unlikely to show any benefit on cognitive functions like memory and thinking.

Other findings were presented for the first time, such as the MAyflOwer RoAD study which found that a drug sembragilline failed to show any cognitive benefits in a for people in the moderate stages of Alzheimer’s disease. There were hints that it may help to reduce the development of behavioural problems but as the study was not designed to test this outcome, the findings would need to be reproduced.

The Alzheimer’s Disease Cooperative NGF Study was a tour de force, testing surgical delivery of the gene for Nerve Growth Factor directly into the brain of people with mild to moderate Alzheimer’s disease. Unfortunately the intervention failed to show any benefits on memory or thinking in those who received the gene compared to a control group who underwent a sham surgery.




Hints of efficacy from Biogen


The pharmaceutical company Biogen presented positive data from the PRIME study designed to test the safety of an antibody therapy called aducanumab. When they looked at data from just those in the very early disease stages, they observed a reduction in the amount of beta-amyloid plaques in the brain, one of the classic hallmarks of Alzheimer’s disease.

Although this study was only designed to test safety, there was a significant reduction in decline in memory and thinking skills in those who took the drug compared to controls over 52 weeks. These effects were dose-dependent, meaning that the higher the dose, the greater the benefits seen on both beta-amyloid plaques and cognition. These findings now need to be replicated in a much larger study which has just begun recruiting participants in the US and will come to Europe next year.




Lifestyle programmes can slow down cognitive decline


Two large studies are testing whether complex lifestyle interventions can help older people to maintain cognitive health. The ongoing FINGER study from Finland has previously reported improved cognition in an elderly population using a combination of physical activity, brain training, nutritional guidance and monitoring of other health conditions such as high blood pressure and type 2 diabetes.

New data presented showed that those who took part in the programme were at a 30 per cent reduced risk of experiencing cognitive decline over two years compared to the control group who received ten sessions of general health advice. Relative to the control group, over the two years the intervention group saw a 150 per cent increase in brain processing speed, a 40 per cent increase in memory and a 50 per cent reduction in the likelihood of developing problems with everyday tasks such as shopping, cooking and managing finances.

The Multidomain Alzheimer Prevention (MAPT) Study from France has tested a similar intervention either with or without omega-3 supplements in almost 1700 people aged 70 years or older. Presenting their final results for the first time, the researchers reported an increase in brain activation and prevention of cognitive decline over three years compared to the control group. Given how intensive the programme was, the fact that 71 per cent of people stuck to it is very encouraging for the possible delivery of such programmes in the population at large. Omega-3 supplements had no effect overall in this study.

Based on the promising results of these studies and others, the MIND-AD project is now aiming to test a similar complex lifestyle intervention in 10,000 people across Europe with funding from JPND.




Addressing the challenge of slow recruitment


Eric Siemens from Eli Lilly went through the last decade of pharmaceutical industry trials in Alzheimer’s disease, discussing the 13 compounds that have reached phase two or three testing and the reasons why we believed they failed. Although he outlined some current, promising trials that are due to report in the next few years, he stressed that the time taken to conduct these trials is far too long.

Slow recruitment of participants can significantly delay progress in dementia trials. He nodded to recent efforts to streamline recruitment through patient registries (such as Join dementia research) but urged the medical community to encourage all people with early memory complaints to take part in research studies.

Final thoughts


Overall there were a large number of negative trials presented but also some hints of new drugs that might be able to slow down the disease. These were only exploratory studies so we hope the encouraging results will be replicated in larger trials over the coming few years. There are still some major challenges in dementia trial recruitment that need to be addressed but the research community seems determined to solve them.