A platform trial published in _The Lancet Neurology_ looks at the efficacy of anti-amyloid drugs that could delay the onset of Alzheimer’s disease.
**Prof Robert Howard, Professor of Old Age Psychiatry, UCL, said:**
“The press release claims that gantenerumab treatment can delay or prevent the appearance of dementia, but this is not supported by the data and could give false hope to patients and their families about what treatments for Alzheimer’s disease are able to do.
“Anyone who understands how to look at the results of a clinical trial will recognise that this paper reports the failure of gantenerumab to show treatment efficacy on any prespecified clinical outcomes in randomised controlled comparisons between drug and placebo. And, sadly, because of this and other negative trials, development of gantenerumab has been abandoned.
“However, the authors carried out many further analyses from a small number of participants who chose to continue treatment in an open-label extension to the randomised controlled trial. Because this was an open-label extension, there was no randomly allocated placebo group to compare the effects of treatment to. Instead, the results from an “extended control” group were used for comparison and a large number of differently defined treatment groups were run through the analyses, increasing the risk that any apparent differences with treatment would be due to chance. For these reasons, no responsible clinical trialist should claim on the basis of these data to have shown a 50% lowering of the risk of developing dementia symptoms. If you look at the wording of the Summary of the published paper, you will see that such a claim does not appear, as presumably the scientific peer reviewers and editorial staff would not have permitted such a misleading overstatement to be published in the Journal.
“I hope that journalists will question why the conclusions of the peer reviewed article are so different from the headline content of the press release and won’t disseminate what is unhelpful misinformation about the potential of a drug to prevent Alzheimer’s disease.
**Dr Richard Oakley, Associate Director of Research and Innovation, Alzheimer’s Society, said:**
“As with all antiamyloid trials, this study stemmed from research funded by Alzheimer’s Society, shedding light on the role of amyloid in Alzheimer’s disease.
“These exciting early-stage results hint that long-term antiamyloid treatments, started before Alzheimer’s disease symptoms appear, could potentially delay symptom onset.
“However, these results need to be treated with caution; this trial focuses on a very small group of individuals with genetic forms of Alzheimer’s disease. Longer-term follow up of this group and larger studies will tell us more about the effect of these drugs in these types of Alzheimer’s.
“Ultimately, the field hopes to see similar progress in preventative trials of antiamyloid treatments in people at risk of Alzheimer’s disease later in life, which affects the majority of people with dementia.
“This is a hugely exciting time in dementia research and there is hope on the horizon for all affected by this condition – research will beat dementia.”
**Prof Charles Marshall, Professor of Clinical Neurology, Queen Mary University of London, said:**
“This study focusses on a rare group of people with genetic mutations that cause Alzheimer’s disease that runs in famiilies. These people are of particular interest because we know for certain that they will develop Alzheimer’s disease, and can estimate when they are likely to develop it, making them an ideal group to evaluate preventive treatments.
“It seems from these results that if treated for long enough with a drug that reduces amyloid beta protein in the brain we can delay the development of symptoms in those who will go on to develop Alzheimer’s disease, and this is very exciting. There are two major limitations of the study. The first is that it was a secondary evaluation of a relatively small number of people who were treated for a long time, and therefore the results are not as certain as they would have been if they were the main trial result. The other limitation is that gantenerumab is not nearly as effective as some of the other amyloid reducing treatments that are now available, suggesting that we may be able to do even better than these results suggest.
“I look forward to seeing more results from the other treatments that are now being given in this trial. It is giving tremendous hope to the families that have these rare genetic mutations, and these results suggest that in years to come we may have preventive treatments to offer them.”
**Prof Tara Spires-Jones, Director of the Centre for Discovery Brain Sciences at the University of Edinburgh, Group Leader in the UK Dementia Research Institute, and President of the British Neuroscience Association said:**
“This study by Bateman and colleagues shows promising preliminary results of an experimental treatment in people with rare inherited forms of Alzheimer’s disease. People who inherited a gene that causes early onset Alzheimer’s disease received the drug gantenerumab to remove sticky amyloid pathology before they developed symptoms. Scientists observed that the 22 people who took the drug for the longest (an average of 8 years) had delayed progression of cognitive symptoms. While this study is important scientifically as evidence that amyloid-lowering drugs may potentially be able to delay symptom onset, there are several important limitations to consider. As the authors acknowledge, the delay in symptom onset with treatment was only found in people who were treated for an average of 8 years, probably because amyloid pathology accumulates in the brain for at least 10 years before symptom onset. This study also did not include a control group receiving placebo alongside the drug which is a very important control. Further, the drug used in this study, gantenerumab, has been discontinued by the company that developed it because it did not slow symptoms of the more common non-genetic forms of Alzheimer’s disease in a trial with over 1,900 participants. While this study does not conclusively prove that Alzheimer’s disease onset can be delayed and uses a drug that will not likely be available, the results are scientifically promising.”
**‘****Safety and efficacy of long-term gantenerumab treatment in dominantly inherited Alzheimer’s disease: an open label extension of the phase 2/3 multicentre, randomised, double-blind, placebo-controlled platform DIAN-TU Trial’** **by Bateman et al. was published in _Lancet Neurology_ at 23:30 UK time on Wednesday 19th March.**
**Declared interests:**
**Prof Robert Howard** “No COIs”
**Dr Richard Oakley** “this study stemmed from research funded by Alzheimer’s Society” as this is factually accurate.”
**Prof Charles Marshall “**I have no relevant conflicts”
**Prof Tara Spires-Jones** “I have no conflicts with this study but have received payments for consulting, scientific talks, or collaborative research over the past 10 years from AbbVie, Sanofi, Merck, Scottish Brain Sciences, Jay Therapeutics, Cognition Therapeutics, Ono, and Eisai. I am also Charity trustee for the British Neuroscience Association and the Guarantors of Brain and serve as scientific advisor to several charities and non-profit institutions.”