Scientists have questioned whether a “breakthrough” Alzheimer’s drug will ever make it to patients after more details of its side effects have been released.
Final clinical trial results for lecanemab show that the drug was able to slow the rate of decline in people’s memory and thinking as well as function over 18 months, and also helped people with day-to-day activities. Dementia experts hailed a potential “historic moment” when some of the final results were published in September, but questions remained about lecanemab’s side effects.
The full results, published at the Clinical Trials on Alzheimer’s Disease conference in San Francisco overnight, confirm a “robust effect” of slowing of cognitive decline of 27 per cent compared to those people in the study who were not given the drug. The trial, known as Clarity AD included 1,795 people with early-stage Alzheimer’s and mild cognitive impairment (MCI) due to Alzheimer’s, who received a bi-weekly infusion of either lecanemab or a placebo.
The paper, published in the New England Journal of Medicine, gave more details of a prominent side effect of lecanemab known as amyloid-related imaging abnormality (Aria), which involves a bleed or build up of fluid in the brain. It can vary from mild and negligible to quite severe.
Some 12.6 per cent (or 1 in 8) of those who received lecanemab developed Aria, while 1.7 per cent (less than 1 in 50) developed it in the placebo group. Although there were a similar number of deaths in both groups – eight in the lecanemab group and seven in the placebo group – scientists said further follow up is needed to understand whether Aria in certain patients is life threatening.
If so, it may be that patients receiving such treatments need to be excluded. Further studies will be able to identify the patients at risk and those patients who will maximally profit from the treatment.
The paper also suggests further studies to evaluate how effective and safe lecanemab is ongoing, as a key question is whether clinical benefits are progressive in that they continue beyond the 18 months, and whether they are sustained.
Rob Howard, professor of old age psychiatry at UCL, asked whether the drug was safe. He said: “Recent reports of two deaths from strokes, attributed to a side-effect of the drug, are concerning. The data published on Wednesday indicates that six lecanemab-treated patients suffered strokes during the trial compared with two in the placebo group. Treatment therefore does carry risks, and in some rare cases this can be severe or life-threatening.
“I suspect that the lack of demonstrable clinical effectiveness will mean that lecanemab will not be taken up widely within healthcare systems around the world, although there will always be those whose heart rules their head. We need to keep looking for better and safer dementia treatments and today’s results show that we are now on a believeable path to doing so.”
Lecanemab, produced by Tokyo-based pharmaceutical company Eisai and US biotech firm Biogen, is the first drug that provides a real treatment option for people with Alzheimer’s, experts said. While the clinical benefits appear somewhat limited, it can be expected that they will become more apparent if the drug is administered over a longer time period.
Prof Tara Spiers-Jones, deputy director at the University of Edinburgh’s Center for Discovery Brain Sciences, said: “While [the results are] good news from a well-conducted trial, it is important to note that this is not a cure. Both groups in the trial had worsening symptoms, but people taking the drug did not decline as much in their cognitive skills.
“As the authors point out, there is not an accepted definition of clinically meaningful effects in the cognitive test they used, and it is not clear yet whether the modest reduction in decline will make a big difference to people living with dementia. Longer trials will be needed to be sure that the benefits of this treatment outweigh the risks.
“As a scientist working on Alzheimer’s disease for many years, it is wonderful news that years of fundamental neuroscience research have resulted in a treatment can slow the progression of Alzheimer’s disease and reverse some of the pathological changes in the brain. This result will boost research and gives hope that the treatments based on ongoing neuroscience research will be even better. ”
Professor Bart De Strooper, director of the UK Dementia Research Institute, said: “The overall conclusion is extremely positive. This trial proves that Alzheimer’s disease can be treated. I hope we will start to see a reversal in the chronic underfunding of dementia research. I look forward to a future where we treat this and other neurodegenerative diseases with a battery of medications adapted to the individual needs of our patients.”