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A press release from Eisai and Biogen has announced positive topline results from their Phase 3 clinical trial of lecanemab for early Alzheimer’s disease.
Prof Tara Spires-Jones, Group Leader at the UK Dementia Research Institute at the University of Edinburgh, said:
“Since the data are not yet available to the scientific community, I can’t comment yet on how robust the findings are. If the data hold up to scrutiny, this is indeed fantastic news. The companies report that the drug slowed progression of symptoms of Alzheimer’s disease by almost 30. While this is not a “cure” in that it doesn’t bring people back to normal, slowing cognitive decline and preserving the ability to perform normal daily activities would still be a huge win because people could live well for longer with Alzheimer’s disease. If these data stand up to peer review, the drug could make a big difference and will be a fantastic example of how fundamental research into the brain can make people’s lives better.”
Dr Charles Marshall, Clinical Senior Lecturer and Honorary Consultant Neurologist, Wolfson Institute of Population Health at Queen Mary University of London, said:
“The headline results suggest that this is the first treatment that unequivocally slows down the progression of Alzheimer’s disease. This is very exciting because it represents the first compelling evidence that Alzheimer’s disease can be successfully treated, and in particular that removing abnormal amyloid protein from the brain is worth pursuing further as a treatment strategy. However, it is not yet clear how much patients with Alzheimer’s disease stand to benefit from this announcement. Careful scrutiny of the results when they are presented in detail at a conference in November, and when they are eventually published as a research paper will help to clarify this. The stated benefits are fairly small, and will need to be balanced against the risks of side effects including inflammation and bleeding in the brain. Ensuring that patients receive the full benefit of this type of treatment will also require substantial redesign of dementia services, both to deliver treatments, and to ensure that patients are diagnosed with Alzheimer’s disease as early as possible when they stand to benefit most. We hope that this announcement will be a catalyst for further investment in memory clinics and in research to support early detection of Alzheimer’s disease.”
Prof Peter Passmore, Professor of Ageing and Geriatric Medicine, Queen’s University Belfast (QUB), said:
“This is clearly a preliminary report. We will always reserve full comment until the results are published in a peer review journal so any comments need to be taken with that proviso.
“An initial thought would be that this is encouraging as in this study there are reported clinical benefits, with the primary endpoint being met as well as it seems, all secondary endpoints. This study looks like it should enhance our knowledge of the mechanisms in Alzheimers disease, given the mode of action of lecanemab, so that in itself would be important. The study has been more inclusive in terms of recruitment criteria which is also very interesting compared to some previous trials.
“Apparently the results are to be presented at CTAD so a more informed comment would be expected after seeing that although the full paper remains the most important. Given the importance one would expect to see the paper published very quickly.
“Compared to aducanumab which was approved by FDA on proof of principle without any clinical benefits being shown this appears to show clinical benefits. These seem to be small and the debate will be around how clinically relevant the changes are in CDR SB
“The other main factor to consider will be the side effects – its always a question of what benefit at what cost to the patient. Reported side effects seem lowish but again we have to see the full details on those particularly the ARIA.
“So there seems more credibility at face value to the report. The issue will be approval and criteria for use – there is precedent for FDA given the approach to aducanamab. Cost will be a huge factor if approved. If approved in UK for example one needs to consider the issues around the exact licence, NICE, new services would need to be set up to administer the injections frequently and also the required radiology and clinical monitoring that would be needed so this will all need to be factored in on top of the simple cost of the drug.”
Prof Masud Husain, Professor of Neurology, University of Oxford, said:
“While the summary of the results certainly seems very encouraging, we have to be cautious until we are allowed to review the data fully. It is also important to bear in mind that the trial results apply only to people with mild Alzheimer’s disease, not everyone with the condition, and that there were important side effects of the drug, including bleeds in the brain.”
Prof Bart De Strooper, Director of the UK Dementia Research Institute, said:
“This is hugely positive news for the millions of people affected by Alzheimer’s disease worldwide. It is a devastating condition, impacting many aspects of daily life including the ability to form memories, problem-solve and look after ourselves. Effective treatments are therefore desperately needed.
“The results released so far from the lecanemab study show a 27% slowing of cognitive decline compared to people who did not receive the treatment over 18 months, meaning the trial hit its main goal. We will have to wait until the end of November to assess the data in more detail, but I am hopeful that the drug will be approved by the US Food and Drug Administration next year.
“This is also a very encouraging result for the Alzheimer’s research community, demonstrating that we are moving in the right direction by targeting clearance of the amyloid beta protein. There is real momentum in the field and several exciting trial results on the horizon in the coming year.
“It’s important that we aim to administer lecanemab, and drugs like it, as early as possible in the disease course. Changes to the brain begin decades before symptoms appear in Alzheimer’s. Therefore, intervening rapidly gives these medicines the best chance of slowing brain degeneration before too much damage is done, and positively impacting the lives of those affected.
“The diversity of the study population, 25% of whom were Hispanic and African Americans, is also a mark of progress in the field and will give us essential information on how different populations may respond to the drug. This is crucial to understand, since there is growing evidence that the biological pathways underlying neurodegenerative disease vary by ethnicity.”
Dr Catherine Mummery, Consultant Neurologist, National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust (UCLH), said:
“The lecanemab CLARITY results are exciting, if borne out by the full details of the study, as they are the clearest indicator so far that by lowering amyloid levels in the brain, cognitive decline can be slowed. The results are consistent in size with those found in earlier phase trials with other anti amyloid drugs, and with the positive, controversial trial in aducanumab. This convergence strengthens the findings. However, the size of the effect, while significant, is small – the disease is slowed by 27% over 18 months. What we cannot know yet is whether that effect increases over time in an individual; that would be predicted but is untested – time will tell.”
Prof Rob Howard, Professor of Old Age Psychiatry, UCL, said:
“This is an unambiguously statistically positive result and represents something of an historic moment when we see the first convincing modification of Alzheimer’s disease. God knows, we’ve waited long enough for this.
“Important now that Eisai move quickly to publish the full data, including sensitivity analyses to look at the effects of functional unblinding in those participants who developed ARIA side-effects.
“Having shown efficacy, the next question is whether there is clinical effectiveness. A 0.45 point advantage on an 18-point scale, where the accepted minimum worthwhile difference ranges from 0.5 to 1.0 points, will mean that there are going to be some very difficult conversations and decisions in the next weeks and months.”
Prof John Hardy, Professor of Neuroscience, UCL, said:
“The results from Eisai and Biogen on their phase 3 results for lecanemab are truly encouraging and look like the first truly positive mechanistic trial results in Alzheimer’s disease. It will be great to see the full results in late November and even better when a peer reviewed paper is published. The results look modest but real.
“It has been a long road for anti-amyloid therapies. This is clearly not a magic bullet. But it looks like a definite “end of the beginning”.”
Dr Susan Kohlhaas, Director of Research at Alzheimer’s Research UK, said:
“This is a historic moment for dementia research, as this is the first phase 3 trial of an Alzheimer’s drug in a generation to successfully slow cognitive decline. These results show that lecanemab slows the progression of memory and thinking problems in people with early Alzheimer’s, demonstrating a major breakthrough in dementia research. This is the first drug that’s been shown to not only remove the build-up of a protein called amyloid in the brain, but to have a small but statistically significant impact on cognitive decline in people with early-stage disease. The drug can also cause substantial side effects which will need to be considered. These top-line results, announced by the pharmaceutical company that make the drug, Eisai, offer new hope to people affected by this cruel and devastating disease.
“Before a drug is made available, regulators in different parts of the world, including the UK, will still need to assess the full data to determine whether lecanemab is safe and effective enough to be used in people with Alzheimer’s. If the drug is approved, it is essential that it gets to the people who may benefit from it as quickly as possible. Now is the time to be making sure that our health system is set up to deliver life changing treatments. In preparation for this, it’s vital that the Government’s new Dementia Mission focuses on ensuring the NHS is ready to roll out new licenced therapies as quickly as possible – right now only 1 in 3 psychiatry services would be ready to deliver a new treatment within a year.
“Today’s results were only possible because of the volunteers who took part in this trial, previous studies of this drug and wider dementia research across the world. Eisai is now recruiting people with a high risk of Alzheimer’s who have not yet developed symptoms to take part in further trials, to determine whether the drug slows the disease when given at an even earlier stage. People can register their interest to take part in studies like these by signing up to Join Dementia Research by calling 0300 111 5 111.
“This drug has only been tested for people in the early stages of Alzheimer’s and won’t be a silver bullet for all causes of dementia. At Alzheimer’s Research UK we will keep working to bring about more breakthroughs for people with all forms of dementia, including those in the later stages of disease. We hope today’s news will spark renewed investment in dementia research across the globe and political leadership to deliver the funding and infrastructure needed to make life-changing new treatments a reality.”
Dr Tom Russ, Consultant Psychiatrist & Honorary Clinical Reader and Director of Alzheimer Scotland Dementia Research Centre, said:
“These preliminary results offer people living with dementia some hope. The full results are due to be presented at the CTAD conference in November and it will be great to hear more detail there. The prospect of a disease-modifying drug for Alzheimer’s disease is an exciting one, which could improve many lives. However, health services need to start thinking now how such drugs could be provided fairly, allowing everyone areas equal access to new treatments whether they live in remote, rural, or economically deprived areas.”
Dr Liz Coulthard, Associate Professor in Dementia Neurology, University of Bristol said:
“This is a gold standard study in people with fairly early signs of Alzheimer’s disease. Although not curative, lecanemab slowed decline in day-to-day function compared to placebo. So lecanemab potentially offers prolonged good quality life in people with early signs of Alzheimer’s disease. This heralds a transformation in outlook for people with the first signs of Alzheimer’s disease.
“As clinicians we have been aware that this class of drugs looked promising for years now. We have been preparing to diagnose and treat people in the early stages, and we are really keen to be able to offer this to our patients. However, there are still huge changes needed to be able to give therapy to people with Alzheimer’s disease. Up to now, many people have not come forward when they first worry about their memory as there were no treatments for dementia. It is very likely more people will come to see their doctor now – and we, as doctors, need to be ready. Most people with mild memory symptoms will not have Alzheimer’s disease. We need to develop an effective and quick triage system so we can reassure people without Alzheimer’s and offer treatment to those with Alzheimer’s.
“Our health system moved impressively rapidly to deliver trials and therapies for COVID. Let’s hope we can apply the same efficiency for people with Alzheimer’s disease.”
Declared interests
Dr Charles Marshall: “I have received grant funding from Bart’s Charity, NIHR, Innovate UK, Alzheimer’s Research UK, Michael J Fox Foundation, Davos Alzheimer’s Collaborative, and Tom and Sheila Springer Charity. I have received personal fees for providing educational content from GE Healthcare and Biogen.”
Prof Peter Passmore: “I have received honoraria from Biogen in relation to educational activities around aducanamab. I previously received honoraria from Eisai in relation to Donepezil.”
Prof Masud Husain: “No conflicts of interest.”
Prof Bart De Strooper has been a consultant for Eisai (but not on their antibody program)
Dr Catherine Mummery: “I am on the advisory boards for Biogen (aducanumab), Roche (gantenerumab). I have no direct link with Eisai or with lecanemab.”
Prof Rob Howard: “No conflicts.”
Prof John Hardy: “I consult for Eisai but have not been involved in this programme.”
Dr Tom Russ: “No conflicts of interest.”
Dr Liz Coulthard: “I have delivered trials for Eisai and Biogen and have received grant funding from Biogen.”
For all other experts, no reply to our request for DOIs was received.