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The U.S. Food and Drug Administration (FDA) have approved lecanemab via the Accelerated Approval pathway for the treatment of Alzheimer’s disease.
Prof Gill Livingston, Professor in Psychiatry of older people, UCL, said:
“The FDA approval was likely but not definite. The FDA had previously granted accelerated approval to another similar drug Aduhelm on a similar basis but had received considerable criticism including from Congress for this decision.
“The accelerated approval a process for rapidly approving drugs for serious illnesses when it is expected to help more than anything which is available and when the outcome is a surrogate outcome, that is a biological marker rather than patient benefit. Lecanemab showed a large reduction in amyloid plaque protein in the brain which is thought may be a or the cause of Alzheimer’s disease, although there is considerable controversy about this theory.
“Lecanemab had better clinical results than aduhelm. Lecanemab was tested in a well conducted randomised clinical trial and showed a small reduction in cognitive decline on patients with Alzheimer’s disease who took it compared to those on the placebo. There was also an increase in brain swelling and bleeding in people on the active drug -called ARIA (amyloid related imaging abnormalities).
“I am unsure what this will mean in the US, as insurers and individuals try to work out if the small clinical benefit is worth the risks and costs.
“It is being sold at $26500 per year but this is only part of the cost. The drug is given in two weekly intravenous infusions and this requires a clinician to give it and monitor for side effects during the infusion which occurred in just over a quarter of people in the trial (26.4%) and are most commonly nausea and vomiting and flu like symptoms. It would be good practice to monitor for ARIA using MRI scans and 17.3% of people in the trial on the drug had ARIA with microhaemorrhages and 12.6% had swelling without haemorrhages. In addition, ARIA seems to be more common in people with a particular gene which predisposes to Alzheimer’s disease (APOE4) and people may want to test for the gene first.
“I would say to people in the UK it is exciting to find a drug which is useful for Alzheimer’s disease, and it is natural to want to try anything in this illness as there is so little treatment. However, the benefit shown in the published study is small and is less than the cholinesterase drugs which are available (and we will prescribe if you want them). Lecanamab was tested as a disease modifying medication rather than to help symptoms. However the trial showed the benefit at the beginning and those on the drug did not then do even better compared to those on the placebo. If the disease was changed we would expect the difference between the drug and the placebo group to increase over time if it changes the disease course rather then helped symptom. The side effects are considerable and common of both flu like illnesses and swelling and small bleeds in the brain, although many of the brain side effects were not noticed by patients. Since the trial stopped there have been two reports of patients who have had larger and fatal brain haemorrhages which have been thought to be caused by the drug. It is not currently available on the NHS. It has been approved by the FDA because of brain changes not because of helping patients, so it is very early days.
“Drug approval in the UK is about cost in relation to benefit for the patient and will be harder to get as this big change in this trial is in plaques in the brain.”
Dr Dave Powell, LifeArc’s Chief Scientific Officer, said:
“We are delighted that lecanemab has been approved by the FDA as a treatment for people with a confirmed diagnosis of mild cognitive impairment or early-stage Alzheimer’s disease and are proud to have had a role in its discovery. The decision means doctors in the US will be able to prescribe the drug to people who can afford to pay for the drug directly or have appropriate medical insurance.
This news offers hope to millions of patients and their families around the world, as it’s the first drug to show a cognitive clinical benefit for people affected by this devastating condition. We hope the UK’s medicines regulator will make a quick decision on the drug, so eligible people in the UK can also benefit from this new medicine if the benefits for people with Alzheimer’s disease are clear and they are not outweighed by safety concerns.”
Dr Mark Dallas, Associate Professor in Cellular Neuroscience, University of Reading, said:
“The FDA approval of a second anti-amyloid therapy does not come as a surprise given the encouraging data that was reported at the end of 2022. The accelerated approval process indicates that in clinical trials the drug demonstrated the ability to modulate a hallmark of the underlying pathology of dementia and the FDA believe that a real time benefit to people living to dementia will follow. The trials were carried out in people in the early stages of dementia and approval highlights the drug should be used to manage the disease in this population, therefore it will not be a magic bullet for all those living with dementia. I am sure that those people living with dementia and their families in the UK are eagerly anticipating national approvals. This promising news is yet another step towards offering disease modifying treatments for those living with dementia.”
Richard Oakley, Associate Director of Research at Alzheimer’s Society, said:
“Lecanemab is now the second drug aiming to slow down Alzheimer’s disease to be approved in the US, another step forward in the generation of new treatments for one of the biggest global health challenges. We’re proud that Alzheimer’s Society funded research by Professor Sir John Hardy over thirty years ago, identifying amyloid as a key player in the development of Alzheimer’s disease, has led to this moment today.
“People affected by Alzheimer’s disease in the UK will be wondering what this means for them – particularly given European regulators did not approve aducanumab which was also approved in the US. There are still many hurdles before lecanemab could be available on the NHS. We need the regulatory authorities in Europe and the UK to prioritise a rigorous, independent review of the lecanemab data, and for NICE to prepare to evaluate its cost-effectiveness.
“Frustratingly it is possible that lecanemab could be approved in the UK without a system in place to get it to people who need it most. The upcoming ten-year plan for dementia must prioritise boosting stagnant dementia diagnosis rates and preparing the NHS to deliver and monitor the impact of these drugs. Preparation is crucial not just in the short term for the potential arrival of lecanemab, but for the future as 117 other disease slowing drugs are currently being tested in trials. The promised doubling of dementia research funding through the National Dementia Mission must be streamlined into new ways to diagnose Alzheimer’s disease earlier, new treatments and also research into other types of dementia, to give hope for everyone living with dementia now and in the future.”
Hilary Evans, Chief Executive at Alzheimer’s Research UK, said:
“Today’s decision by the regulators in the US, who have deemed the Alzheimer’s drug lecanemab sufficiently safe and effective, marks another important milestone in the global effort to bring about treatments that target the underlying diseases of dementia.
“Many people with Alzheimer’s and their families will be following this story with interest and we know today’s news may prompt mixed emotions. There is still some way to go before lecanemab might reach patients in the UK. This period of uncertainty, while we wait for the UK regulator to conduct its own review, may be difficult for individuals with Alzheimer’s and their loved ones.
“The trial data has shown that lecanemab has a small but measurable impact in slowing the progression of Alzheimer’s. But in practice, lecanemab’s benefits are likely to be measured in extra months rather than years. Yet as anyone affected by Alzheimer’s knows, this time can be precious.
“Set against this, it’s also clear that lecanemab can cause side effects which can, for some, be extremely serious. This is why the FDA has included a safety warning as part of its guidance to doctors when prescribing. UK regulators will need to look independently at the full clinical trial data to reassure themselves that the benefits of lecanemab outweigh the risks for people living with early Alzheimer’s disease in the UK.
“Alzheimer’s Research UK has written to lecanemab’s manufacturer, Eisai, calling on them to work with the UK government, UK drug regulators and the NHS to ensure an evidence-based decision on lecanemab’s safety and efficacy can be made as a matter of urgency. Initiatives like the government’s Dame Barbara Windsor Dementia Mission mean this country is well placed to lead the adoption of innovative new dementia drugs, and we look forward to working with stakeholders to ensure the NHS is properly set up to deliver drugs like lecanemab in the future.
“Lecanemab gives the research community great confidence that we will, one day, be able to deliver a range of treatments that tackle different aspects of Alzheimer’s, as well as other diseases that cause dementia. Researchers worldwide, including those funded by Alzheimer’s Research UK, are working hard to bring these forward. There are now more than 140 experimental drugs in clinical testing today, and we firmly believe that significant advances in dementia treatments will prevail over the next decade. This will help to ensure people living with this devastating condition have a range of effective treatment options to choose from.”
Prof John Hardy, Professor of Neuroscience, UCL, said:
“This is great news and will reset Alzheimer’s research. Now will come the difficult tasks of ensuring the drug is given to the right patients at the right time and that monitoring those patients is also in place.
“We will now face the same decisions in Britain and across Europe and it will be interesting how those decisions play out
“This speedy approval is a testament to the quality of the data presented in the clinical trial reported in NEJM last month.”
Declared interests:
Prof Gill Livingston: “no declarations of interest.”
Dr Dave Powell is Chief Scientific Officer at LifeArc, a medical research charity that transforms promising life science ideas into medical breakthroughs that change patients’ lives. LifeArc played a small but important role in the discovery of lecanemab, having collaborated with biotechnology company BioArctic Neuroscience to humanise an antibody that generated a clinical candidate that ultimately became lecanemab. Read more in this article: LifeArc plays key role in discovery of new Alzheimer’s treatment – LifeArc
Dr Mark Dallas: “I have received funding from Alzheimer’s Research UK.”
Prof John Hardy: “I have consulted for Eisai.”
For all other experts, no reply to our request for DOIs was received.