‘Too early’ to say Alzheimer’s drugs don’t work, say GP experts

Two GPs with an interest in dementia have challenged the conclusions of a new Cochrane review of studies into the effects of amyloid-targeting medication on people with Alzheimer’s, saying more time is needed before such an assessment can be made.
 
The review concluded that the drugs ‘make no meaningful difference’ in the cognitive function of people with Alzheimer’s, while also increasing the risk of bleeding and swelling in the brain.
 
‘The effect of amyloid‐beta‐targeting monoclonal antibodies on cognitive function and dementia severity … due to Alzheimer’s disease is trivial, while on functional ability, it is small at best,’ wrote the research team from the IRCCS Institute of Neurological Sciences of Bologna, Italy. 
 
‘Unfortunately, the evidence suggests that these drugs make no meaningful difference to patients,’ said lead author Francesco Nonino.
 
Further, the researchers conclude that any future trials of treatments for the disease that is now the leading cause of death in Australia ‘should focus on other mechanisms of action’ than the removal of amyloid beta, believed to be the hallmark of Alzheimer’s.
 
‘Successful removal of amyloid from the brain does not seem to be associated with clinically meaningful effects in people with mild cognitive impairment or mild dementia due to Alzheimer’s disease,’ they wrote. 
 
The team of researchers included 17 studies involving 20,342 participants in their review, to assess the clinical benefits and harms of several amyloid‐beta‐targeting monoclonal antibodies in people with mild cognitive impairment or mild dementia due to Alzheimer’s disease.
 
However, a specialist GP in dementia, Dr Stephanie Daly, told newsGP that as research into the medications only began about 10 years ago, it included earlier, less effective iterations of the drugs.
 
‘The first iterations of these medications didn’t really work,’ she said.
 
‘They were good at the target – reducing the amyloid – but they didn’t prove any clinical benefit.’
 
Crucially, of the 17 studies included in the review, only the two most recent studies – the Trailblazer study into donanemab and the Clarity AD study on lecanemab – showed any clinical benefits.
 
‘That may be because the last two have started to do something different,’ Dr Daly said.
 
‘There are lots of possibilities. It could be there’s something that’s been unlocked in the science that they’ve learned from those previous failed studies, and either selected better patients, or they've improved the drug technology.
 
‘So it’s kind of difficult to draw a conclusion and say, “These drugs definitely don’t work” when we’ve only had two studies – the most recent ones – where something has happened.
 
‘[We] probably need more time to make that assessment.’
 
In Australia, donanemab (sold as Kisunla) and lecanemab (sold as Leqembi) are both approved by the Therapeutic Goods Administration (TGA).
 
Donanemab was approved by the TGA in May 2025, but an application for it to be added to the Pharmaceutical Benefits Scheme (PBS) was rejected three months later.
 
Lecanemab (sold as Leqembi), gained TGA approval in September 2025, but is also not PBS-listed, so can cost patients $40,000 or more a year to use.
 
However, ‘only a very small percentage’ of patients with MCI or dementia due to Alzheimer’s are eligible for these medications, says GP and medical advisor with Dementia Australia, Dr Marita Long.
 
‘But what they do, from my perspective, is to highlight the advantages related to a more timely diagnosis, to assess the eligibility for these treatments, and the earlier these drugs are administered, perhaps the more effective they will be,’ Dr Long told newsGP.
 
‘I feel like it would be a shame if the research stopped when it’s been the first thing that has shown some promise.’
 
Both Dr Long and Dr Daly disagree with the Cochrane review’s recommendation that future research should not focus on amyloid beta removal, due to the finding that the successful removal of amyloid proteins from the brain did not result in ‘meaningful clinical benefit’.
 
However, the review authors also noted they had found six ongoing studies, and that the review’s conclusions ‘may change’ as new results become available.
 
‘One of the things that’s right about that Cochrane review is that we don’t want to be too focused on just one process,’ Dr Daly said.
 
‘But we shouldn’t just say, “Well, they don’t work, and we’re not going to bother with them,” because I think it’s too early to say that.’
 
Dr Long said there are ‘many other hypotheses out there’ for the causes of  Alzheimer’s disease.
 
‘But this is the first time we’ve seen some glimmer of hope,’ she said.
 
For Dr Daly, she agrees the study findings are ‘a great reminder for GPs that there’s hope’.
 
‘We should still be evaluating people for cognitive symptoms. We should be talking to them about trials. We should be talking to them about drugs, if they’re interested in that,’ she said.
 
‘And we should have optimism that things are going to change in the future; it’s too early to say that it’s all terrible and we have to give up.
 
‘[Amyloid-targeting drugs] are not a miracle cure, but they are a doorway and an opening to future research. Hopefully it’s the start of something good.’
 
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