Here, UK DRI researchers comment on the news.
Prof Giles Hardingham, Interim Director of the UK DRI, said:
“It is terrific to see these results published in full today. We have waited a long time for Alzheimer’s treatments, so it’s really encouraging to see tangible progress continuing to gather pace in the field. We’re on the edge of exciting and significant change in the landscape of treatment for people affected by or at risk of dementia.
Donanemab is the most recent anti-amyloid drug to be developed, Lecanemab having recently been approved by the FDA. These first-generation drugs are by no means perfect, but represent an important breakthrough that will pave the way for many future therapies.
At the same time, amyloid is just one part of the complex picture of Alzheimer’s. At the UK Dementia Research Institute, we are also undertaking vital discovery research into additional disease mechanisms. This, we hope, will ultimately lead to a suite of treatment options tailored to the individual person dependent on their type and stage of dementia."
Prof John Hardy, Group Leader at the UK DRI at UCL, said:
“The successful outcome of the Eli Lilly’s anti-amyloid antibody donanemab is great news for Alzheimer’s disease and confirms the positive and similar outcome for Eisai’s lecanemab trial late last year. The results are very similar, and that in itself is reassuring. Disease progression is slowed about 30%, but it too has occasionally serious complications which require monitoring. The basic scientists now need to work to understand what we need to do to stop the disease rather than just slow it, but the major immediate task will be to organise NHS Alzheimer provision to be able to use these therapies.”
Prof Tara Spires-Jones, Group Leader at the UK DRI at Edinburgh, said:
"It is fantastic news that another treatment has been successful in slowing the progression of Alzheimer’s disease. The study by Sims and colleagues published in the Journal of the American Medical Association was well-conducted and shows a significant slowing of disease symptoms with donanemab treatment.
The drug is an antibody that attacks amyloid plaques, one of the sticky proteins that clumps in the brains of people with Alzheimer’s disease. As well as slowing symptom worsening, treatment also lowered blood levels of another pathological protein called tau, indicating that the treatment may protect the brain to some extent from both pathologies. While very promising, it is important to note that this treatment has rare serious side effects including small strokes and brain swelling and less serious reactions to the monthly infusion of the drug. This treatment is not a cure and more work is needed to find treatments that can halt instead of just slow progression.
The effects of the current drug are very similar to another treatment recently approved in the US (lecanemab) that also attacks amyloid, adding weight to the idea that Alzheimer’s disease can be effectively treated. Overall, this is an excellent example of translation of years of fundamental neuroscience research into an effective treatment to slow Alzheimer’s disease. With more research, treatments will get even better in future."
Prof Nick Fox, Group Leader at the UK DRI at UCL, said:
“These results are really promising. Rapid and dramatic amyloid removal was achieved and significant slowing of decline. Those who were less affected at baseline derived greater benefit with 30-40% slowing across a range of clinical measures - but the whole (combined) group still saw 20-30% slowing on these measures, which is very encouraging.
The challenge will be to deliver these therapies in already stretched health care systems and to do so safely.”
Dr Marc Aurel Busche, Group Leader at the UK DRI at UCL, said:
“This is encouraging news for people living with Alzheimer’s disease (AD). Donanemab has shown promise in significantly reducing the harmful brain amyloid plaques typically elevated in AD, as well as markedly slowing disease progression, as indicated by multiple clinical readouts.
A critical observation from the study is that patients with a lower burden of tau tangles in their brains - another key pathological hallmark of AD, which has a stronger correlation with cognitive function than amyloid plaques - demonstrate a better response to Donanemab. This emphasises the crucial importance of initiating treatment early and the concept of therapeutic windows and staging in AD management. Nonetheless, for patients at advanced disease stages (the patient population tested in this trial), characterised by high levels of both amyloid-beta and tau proteins, as well as symptoms, the data suggest that combination treatment involving both anti-amyloid and anti-tau therapies may be even more effective - considering that donanemab does not appear to directly impact tau tangles.
From a broader clinical perspective, the data underscore the need to invest in diagnostic tools that can detect AD at a stage before overt clinical symptoms and brain atrophy are present, at a time when amyloid plaques have begun to accumulate but tau tangles have not yet spread significantly across the brain. Potential solutions could include the use of blood protein markers in combination with markers of early brain dysfunction.
While the promise of donanemab is undeniable, it is noteworthy that there were more serious adverse events, such as infusion-related reactions and amyloid-related imaging abnormalities, in the Donanemab group compared to the placebo group, and treatment discontinuation due to adverse events was higher in the Donanemab group. The treatment is additionally linked to a greater decrease in whole brain volume and a greater increase in ventricular volume - observations that have been made with similar monoclonal antibodies but require further exploration and understanding.”
