Drug ‘significantly’ slows Alzheimer’s progression: Study

Editor’s note: This article was updated on 18 July 2023 to include details of a peer reviewed publication of the clinical trial. The original article, published in May 2023, appears below.
 
The results of a promising clinical trial for a drug to treat patients in the early stages of Alzheimer’s disease have been published this week in the American Medical Association’s journal.
 
A randomised clinical trial for the use of donanemab, TRAILBLAZER-ALZ 2, indicates that the drug – which was taken by intravenous infusion every four weeks for 72 weeks by trial participants – could slow the progression of disease by up to 35%.
 
‘Among participants with early symptomatic Alzheimer disease and amyloid and tau pathology, donanemab significantly slowed clinical progression at 76 weeks in those with low/medium tau and in the combined low/medium and high tau pathology population,’ the article states.
 
Dementia Australia CEO Maree McCabe AM welcomed the publication of the trial outcomes.
 
‘These results provide much needed hope for people who are developing symptoms, have mild cognitive impairment or who are in the early stages of Alzheimer’s disease,’ she said. 
 
 ‘This research also highlights the importance of early diagnosis so people can access treatment and support as soon as possible.  
 
‘We need to raise awareness and understanding of dementia to reduce discrimination and stigma so we can ensure people with concerns about their cognition are seeking information and support as early as possible.’
 
The treatment is yet to be approved by the Therapeutic Goods Administration (TGA) for use in Australia.
 
Previous article published 4 May, 2023
The number of Australians diagnosed with Alzheimer’s disease – the most common form of dementia – is on the rise and little progress has been made in treatment development over decades.
 
But clinical trial data for a new drug, called donanemab, has brought hope for people with early symptomatic disease.
 
More than 1180 participants, who had an intermediate level of tau and clinical symptoms of Alzheimer’s disease, were given a monthly injection of donanemab and assessed for how the drug altered their measure of cognition and ability to partake in daily activities, known as the Alzheimer’s Disease Rating Scale (iADRS).
 
And according to a number of experts, the results are ‘promising’.
 
Phase 3 trial results, released by drug company Eli Lilly but yet to be peer-reviewed, show that the drug significantly slowed cognitive and functional decline, with a 35% slowing of decline.
 
Meanwhile, 47% of participants on donanemab showed no decline at one year compared to 29% of the placebo cohort.
 
One of the hallmarks of Alzheimer’s disease is the accumulation of a protein called beta-amyloid – a build-up of sticky protein widely known to drive symptoms of the disease – and donanemab is an antibody that targets the amyloid plaques in the brain, helping to clear them away.
 
Dr Prita Asih, a Research Associate in Dementia Neuroscience at Flinders University, is among those saying the results are promising, likening the findings to those of the Alzheimer’s treatment lecanemab, which was approved for use in the US in January.
 
‘Donanemab even produced amyloid plaque clearance as early as six months after the start of the treatment [34%] and 12 months [71%],’ she said.
 
‘Based on the long-held theory that amyloid reduction may lead to reduced cognitive decline, the most exciting outcome of the trial is slowing cognitive and functional decline in patients with early stage of Alzheimer’s disease.’
 
However, unlike the lecanemab trial, the study into donanemab also enrolled a small number of people (552) with high levels of tau at baseline, representing a later stage of disease progression. When combined with the intermediate tau population, donanemab demonstrated a 29% slowing of decline according to CDR-SB and 22% for iADRS, respectively.
 
Professor Christopher Rowe is Director of the Australian Dementia Network at the University of Melbourne and Dementia Clinical Champion at the Florey Institute of Neuroscience and Mental Health.
 
He noted that the benefits and risks of serious side effects ‘appear similar’ to lecanemab, but that donanemab has the added benefit of requiring less frequent dosing and appears to remove amyloid faster, meaning treatment can be stopped after 12 months in many patients.
 
‘Importantly, the donanemab trial showed greater benefit in those with lower brain tau levels. Tau build up follows amyloid build up in Alzheimer’s disease so this is important evidence that the earlier treatment is given, the greater the benefit,’ Professor Rowe said.
 
‘With new blood tests for Alzheimer’s disease emerging there is a real possibility that very early detection and treatment will reduce the prevalence of severe dementia and turn the tide on this devastating illness.’
 
Dr Marianne Coleman, an eyecare researcher at the Australian College of Optometry’s National Vision Research Institute and the University of Melbourne, agrees. She said the findings emphasise the value of early diagnosis.
 
‘Delaying cognitive and functional decline helps people living with early-stage dementia to continue engaging in other support programs and activities designed to maximise their wellbeing and maintain their independence,’ she said.
 
‘This also includes engagement with allied health services providing vision and hearing care, which are increasingly important forms of post-diagnosis support, as highlighted in the 2022 World Alzheimer’s Report.’
 
Dr Coleman said that delaying progression to subsequent stages of the disease may also extend the ‘window of opportunity’ to address other modifiable risk factors for cognitive decline, such as sensory impairment, through interventions like prompt cataract surgery, hearing screening, and ensuring glasses are up to date.
 
However, there is some concern over the possible side effects.
 
While most side effects experienced were mild-to-moderate and resolved or stabilised, 1.6% experienced serious amyloid-related imaging abnormalities (ARIA) resulting in three deaths – two attributed to ARIA and one following an incident of serious ARIA.
 
Dr Asih said potentially serious side effects include brain swelling and bleeding and that they should be closely monitored, particularly for people who carry the gene mutation APOE4, which is linked to an increased risk of Alzheimer’s disease.
 
Associate Professor Lyndsey Collins-Praino, who is Head of the Cognition, Ageing and Neurodegenerative Disease Laboratory in the School of Biomedicine at the University of Adelaide, is ‘cautiously optimistic’. But beyond the side effects, which are cause for concern, she says that post peer-review ‘key questions remain’.
 
‘As treatment was completed once plaque clearance was achieved, questions also remain about long term benefits, given that cognitive/functional decline is not dependent on plaque pathology alone,’ she said.
 
Alzheimer’s, which is a progressive neurodegenerative disease that affects memory, is now the leading cause of disability and the second most common cause of death in Australia.
 
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Alzheimer’s disease amyloid plaques brain health donanemab treatment