July 31, 2024

expert reaction to press release from Eisai, who have presented findings on three years of continuous treatment with lecanemab

Scientists react to findings presented at the Alzheimer’s Association International Conference (AAIC) 2024 about continuous treatment with lecanemab.

Prof Paresh Malhotra, Head, Division of Neurology, Imperial College London; Consultant Neurologist, Imperial College Healthcare NHS Trust; and Associate Member, UK Dementia Research Institute, said:

“These findings presented at the AAIC conference in Philadelphia help us understand a bit more about the longer-term effects of lecanemab.  They confirm that major side effects are more likely to occur earlier on in treatment rather than after extended periods, and they also show that progression continued at the same rate as in the original trial’s placebo group when treatment was stopped.  The investigators have also compared the effects of long term treatment in an open label extension with observational data from a major cohort.  This is not the same as running a longer duration placebo-controlled clinical trial but does suggest that long-term treatment with lecanemab has ongoing effects on thinking and daily function.  These findings are helpful and do not hold any major surprises but in those places where lecanemab is approved, it is essential that real world data are collected to help us understand more about long-term treatment with this drug.”

Prof Ian Maidement, Professor of Clinical Pharmacy, Aston University, said:

“This is early preliminary data which doesn’t appear to have been peer-reviewed.

“The adverse events continue to be of concern and are not fully reported on the press release.  It is noteworthy that the EMA (European Regulator) recommended refusal of marketing for lecanemab primarily due to these side-effects.

“I found the efficacy data very difficult to interpret; I would have liked the release to quote effect sizes.

“Other limitations: the press release also ignores the key issue of treatment burden and cost.  Lecanemab is given by infusion, most likely on hospital wards and in the USA costs £20,000 per year.”

Dr Richard Oakley, Associate Director of Research and Innovation at Alzheimer’s Society, said:

“In recent clinical trials stemming from early work funded by Alzheimer’s Society 30 years ago, lecanemab has been shown to slow memory and thinking skills decline in people with early Alzheimer’s disease, by targeting a protein called amyloid.

“This is the first study showing the longer-term benefits of lecanemab treatment over three years without additional safety concerns.  This new research suggests people might need continuous treatment with lecanemab, but we need to see further data to confirm this.

“This research also showed that the benefits of lecanemab treatment actually increase when it’s taken over three years.  It’s encouraging that a small subgroup of participants in the very earliest stages of Alzheimer’s disease were found to have either no decline or an improvement in memory and thinking skills over this timeframe – further supporting evidence that an early and accurate diagnosis is critical to maximising benefit from these drugs.

“We’re still waiting to hear if lecanemab will be approved for use in the UK, but it has already been approved in the USA, China, Japan and South Korea.

“We’re at a turning point where people with Alzheimer’s disease could finally have treatments to slow its progression.  But we know that currently people with dementia are not receiving an early or accurate enough diagnosis to access these treatments when they come, and a third of people with dementia in the UK don’t receive a diagnosis at all.

“Alzheimer’s Society is urgently calling on the NHS to commit to plans for how they intend to improve early dementia diagnosis and deliver ground-breaking treatments when they are available, to the people who desperately need them.”

Prof Sir John Hardy, Professor of Neuroscience and Group Leader at the UK Dementia Research Institute at University College London (UCL), said:

“This press release seems to convey a mixture of good and disappointing news.  The good news is that there seem to be no additional adverse events associated with long term administration of lecanemab.  Indeed, it seems that the adverse events are all associated with the initial drug administration, and this may lead to less monitoring being needed later during treatment.  The disappointing news is that it also seems that drug holidays are not helpful.  In the absence of the drug, the rate of decline increases.  Of course, this is a press release and not a published paper.  When the primary data is published, then I am sure everyone will want to dissect it thoroughly.”

Dr Tom Russ, Reader in Old Age Psychiatry and honorary Consultant Psychiatrist, University of Edinburgh, said:

“Following the decision not to license Lecanemab in the EU – and with the UK decision still awaited – these findings are very welcome.  They are consistent with the previous findings from CLARITY-AD and show that the small change observed over 18 months is continued for a further 18 months.  However, this difference between the groups is still very small and probably still too small to be considered clinically meaningful.  This has to be weighed against the burden of having twice-monthly infusions – both for the person receiving them and the service providing them – and the significant adverse effects resulting from the medication.  It is positive to know that there were no new safety findings but those identified previously were concerning.

“It remains the case that, even if this drug were to be licensed in the UK, only a minority of people would be eligible for it and they would have to come to a healthcare setting twice a month to receive it.  We should be providing enhanced support to everyone who has a diagnosis of dementia so that everyone sees a professional twice a month – otherwise the inequality between people receiving Lecanemab (if it is licensed) and those who aren’t would be unacceptable.  There needs to be a revolution in dementia research, care, and support, and we remain optimistic that our new government in Westminster will have the clear sight needed to provide the necessary funding and reform.”

Dr Marc Busche, Group Leader at the UK Dementia Research Institute at UCL, said:

“This is only a press release and we need to await the full dataset, and my comment is based on the press release only.  The clinical effects of lecanemab, as reported, demonstrate a significant slowing of cognitive and functional decline in patients with early Alzheimer’s disease.  The reported reduction of 0.95 points on the Clinical Dementia Rating-Sum of Boxes (CDR-SB) scale is meaningful, allowing patients to maintain their cognitive and daily functioning abilities longer than they would without the treatment.  The requirement for ongoing treatment to maintain these effects is a critical consideration for long-term disease management.  The safety profile appears manageable, but vigilance for adverse events remains important.  These findings contribute positively to the body of evidence supporting amyloid-beta targeting therapies in Alzheimer’s disease.”

Press release: https://www.eisai.com/news/2024/news202456.html

There is no paper.

Declared interests

Prof Paresh Malhotra: “I have received research funding from NIHR, MRC, Dementia Platforms UK, Alzheimer’s Research UK, British Heart Foundation and Alzheimer’s Society.  I am lead for an NIHR-funded trial with drug/placebo provided by Takeda Pharmaceuticals.  I sit on the Alzheimer’s Society Research Strategy Council, am an Associate Member of the UK DRI, and am the National Specialty Lead for Dementia and Neurodegeneration in the NIHR Research Delivery Network.  I also sit on two NHS England policy working groups looking at diagnostic pathways and delivery issues relating to disease-modifying therapies for Alzheimer’s Disease.”

Prof Sir John Hardy: “I have consulted for Eisai.”

Dr Tom Russ: “I am a Reader in Old Age Psychiatry at the University of Edinburgh and an honorary Consultant Psychiatrist in NHS Lothian.  I am Clinical Research Champion of the NHS Research Scotland Neuroprogressive and Dementia Network, funded by the Chief Scientist Office of the Scottish Government.  I receive or have recently received grant funding from Alzheimer Scotland, the Royal Society of Edinburgh, UKRI, BBSRC & ESRC, the Blood Biomarker Challenge, and the Rosetrees Trust.  I am a PI on the Evoke and Evoke+ clinical trials but have no financial links with and receive no payments from pharmaceutical companies.  I attended the UK Appropriate Use Recommendations meeting for Lecanemab and will be a co-author on the resulting article but received no honorarium and my travel expenses were paid by NHS Research Scotland.”

Dr Marc Busche: “I do not have any conflicts to declare.”