select search filters
briefings
roundups & rapid reactions
before the headlines
Fiona fox's blog
Scientists comment on both MHRA and NICE news on lecanemab for Alzheimer’s disease.
Fiona Carragher, Chief Policy and Research Officer at Alzheimer’s Society, responds to the announcements:
“Today’s MHRA approval of the first safe and effective Alzheimer’s disease treatment, shown to slow progression, is a defining moment for people with early-stage Alzheimer’s disease in the UK and a significant step towards a more hopeful future.
“While we welcome the MHRA approval, it is disappointing that NICE has not recommended approving lecanemab for use on the NHS at this stage. The news that lecanemab will be restricted to certain groups of patients will also lead to uncertainty for many people with Alzheimer’s disease and their loved ones.
“We respect the decisions regulators have made, however we know these announcements will bring a mix of emotions for those who have been waiting a long time since the promising trial results were first announced.
“The NICE recommendation reflects the urgent challenges which must be addressed regarding how we diagnose and treat people with dementia. A third of people affected by dementia have not received a diagnosis, and for those who have been diagnosed, it’s often not early or accurate enough for a person to be eligible for new treatments.
“A dementia diagnosis not only opens up the potential for treatment. It is also the single most effective route to the care, support and information we know is so important for everyone living with dementia and their loved ones.
“Now more than ever, Alzheimer’s Society is calling on Governments and health systems across the UK to prioritise dementia by improving early diagnosis in order to deliver ground-breaking treatments at scale.
“We know first-hand the devastation that dementia causes and would encourage anyone with dementia or concerns about potential symptoms to contact Alzheimer’s Society for support and information at alzheimers.org.uk or by calling our helpline on 0333 159 3456.”
Dr Liz Coulthard, Professor of Cognitive Neurology, University of Bristol, said:
“It is positive that MHRA have deemed lecanemab safe for clinical use, albeit with caveats around who can receive it. It has been very difficult for NICE to decide whether the clinical effect of lecanemab is worth the money. My view is that lecanemab should be available on the NHS for patients who may benefit. I hope that we can find a way to make administration of lecanemab more cost effective. My patients tell me that they would like to be offered lecanemab so that they can choose whether or not it is right for them.”
Prof John Gallacher, Director of Dementia Research UK and University of Oxford.
“Whatever your view on the decision taken by MHRA and NICE, the key take-away is that Lecanemab has been licensed. This is encouraging for the development of next-generation therapies that will provide greater benefit at less risk. There are grounds for optimism that these next-generation drugs will become available on the NHS. It is crucial, therefore, that the UK remains laser-focussed on developing these treatments.”
Prof Bart De Strooper, Professor in Alzheimer’s Disease at UCL and UKDRI, said:
“It’s encouraging that the drug is at least available for prescription and use in the UK, which contrasts with the situation on the continent. However, it’s disappointing that NICE and the UK have not seized this opportunity to send a clear signal to NHS that the future for Alzheimer’s Disease is starting and that they better prepare for it. We should start now to improve the diagnosis and support systems for Alzheimer’s patients. While better drugs are on the horizon, it would have been more forward-thinking to see this drug as an opportunity to begin strengthening the support infrastructure now, in preparation for a future where dementia can be effectively managed or even eradicated. It’s also unfortunate that those who could benefit from this treatment but cannot afford it will be left without access. The data and the rumours at the international Alzheimer’s Congress suggest that some patients are very much helped with this treatment. We will learn from the countries who fully support the use of the medication.”
Prof Paul Morgan, Interim Director, UK Dementia Research Institute Cardiff, Cardiff University, said:
“MHRA has today announced approval of the anti-amyloid antibody drug Lecanemab for use in mild cognitive impairment (MCI) and early Alzheimer’s disease (AD), unsurprising given that it was already approved by the FDA for use in the US. Simultaneously, NICE has issued draft guidance stating that the drug is not recommended for NHS use in treating MCI and AD.
“The FDA decision and subsequent MHRA approval was based on the trials evidence showing a modest decrease in rate of progression in MCI and early AD patients treated with Lecanemab for up to 2 years. NICE reassessed this evidence and undertook a cost-benefit analysis, concluding that the socioeconomic case for using Lecanemab was not made.
“Even in the company analysis of the first large trial results, the impact of the drug was relatively small, claiming a 27% slowing of cognitive decline; others have suggested that, when dropouts and other cofounders are taken into account, the impact may be substantially smaller.
“The NICE guidance does not specifically address risks of the drug – which are significant. As many as a quarter of treated individuals can develop signs of a brain vascular injury termed ARIA, mild in most but, in ~2%, severe and occasionally fatal. There have been several deaths from this condition in the US and there is considerable effort to identify and exclude those most at risk, including individuals homozygous for the Alzheimer risk gene ApoE4 and those with preexisting brain vascular problems.
“The anti-amyloid drugs emerged with considerable media hype, unsurprising considering that these were the first to show ANY disease-modifying effect in AD. The combination of high cost of the drug, relatively low impact on disease and significant risk likely justify the NICE guidance. It is possible that, as better ways of identifying those most likely to benefit emerge and the result of longer-term use in the US are revealed, the balance may shift and the guidance change.
“The NICE decision is likely to be disappointing to those affected by AD whose hopes may have been elevated by the early promise of amyloid-targeting therapies; however, given the many unanswered questions around patient selection, monitoring, long-term impact and side effects, the “wait and see” approach is understandable.”
Prof Vanessa Raymont, Associate Professor and Honorary Consultant Psychiatrist, Department of Psychiatry, University of Oxford; R&D Director, Oxford Health NHS Foundation Trust; and Associate Director, Dementias Platform UK, said:
“The MHRA’s approval of lecanemab is ground breaking and massively exciting news, as it is the first new drug for Alzheimer’s disease in over 20 years. It is also the first drug that is approved in the UK that has the potential to change the course of the disease and have real impact on the progression of any memory impairment. However, it is clear the NHS still isn’t ready to roll out treatments like this. More ground-breaking treatments are coming and this is a great opportunity for us to offer improved care for all patients with Alzheimer’s disease.
“New treatments bring hope but they will mean nothing if we don’t urgently fix dementia diagnosis, which is why research projects like the Blood Biomarker Challenge – which aims to bring a blood test for dementia to the NHS within 5 years – are so important. A dementia diagnosis is important because it unlocks access to personalised care and support, allowing people and their families to plan for the future.”
Prof Paresh Malhotra, Head, Division of Neurology, Imperial College London; and Consultant Neurologist, Imperial College Healthcare NHS Trust, said:
“The MHRA, in contrast to the EMA, but in keeping with the decisions made in the USA and elsewhere, have licensed lecanemab, an amyloid-clearing medication in the UK for the treatment of early Alzheimer’s Disease. This will enable patients to be treated in the UK, but the simultaneous judgement by NICE that the benefits are too small to justify cost, means that, for the time being at least, patients will not be able to access treatment via the NHS. These two decisions are reflective of the complex issues surrounding the development of this new Alzheimer’s drugs including the hope that they bring to the community, but also their cost and relatively modest effects on disease progression as well potential side effects. Lecanemab does not actually improve patients’ symptoms but appears to reduce the speed of decline and treatment comes with significant potential risks. There will be much discussion and controversy about these decisions, but for those of us who see patients with Alzheimer’s Disease, it is critical that we get across these complexities as well as the realities of treatment. If patients and families are seeking to be treated privately, it is very important indeed that the risks, potential benefits and implications of treatment (regular intravenous infusions and monitoring scans) are explained carefully, clearly and thoroughly before any treatment decision is made.”
Prof Andrew Doig, Professor of Biochemistry, University of Manchester, said:
“Lecanemab is a new drug for Alzheimer’s Disease (AD) which tackles the build-up of amyloid-b in the brain, the likely root cause of Alzheimer’s. It is an antibody that is administered through a needle inserted into a vein. Lecanemab was tested with a clinical trial on nearly 2000 people with early-stage AD, run over 18 months.
“Lecanemab shows real benefit to patients by slowing down cognitive decline. It is also the first drug that acts by targeting amyloid-b, clearing it from the brain, rather than relieving symptoms of dementia.
“The benefits are small, however, and there are concerns with the drug. Firstly, lecanemab is not a cure for AD and it does not even reverse, or even halt, the disease. All it does is to slow down the rate at which the disease progresses, as measured by cognitive ability. In effect, patients who take lecanemab see a delay in progression to more severe dementia by about six months. Secondly, carrying out a diagnosis to see who is eligible to take lecanemab can only be carried out by a PET scan, similar an MRI scan, or by analysing cerebrospinal fluid, carried out by a lumbar puncture. These diagnosis methods are expensive and can be unpleasant for patients, so are not routinely available. Thirdly, there is a small, but real risk, that lecanemab can cause brain haemorrhage. A few patients on the trial died in this way. Patients who have a higher risk of brain haemorrhage for genetic reasons would not be allowed to take lecanemab. Finally, though we are not told the cost of the drug, it is expected to be high. Given the small benefits of the drug, NICE has not approved lecanemab. NHS resources are limited and are better spent elsewhere.
“This decision will be disappointing for patients and carers who are living with the burden of this horrible disease that has no cure. Nevertheless, there is hope. Better diagnostic methods are in development, such as a simple blood test, which would mean that PET scans or lumbar punctures are not needed. Lecanemab has not been ruled out forever and this decision could change. We will continue to track how well it works over longer time periods. Costs may also come down. In addition, many other AD therapies, such as other antibodies are on the way. Some of them are likely to work better than lecanemab and could be approved.
“Lecanemab has shown that it is possible to slow cognitive decline caused by AD. It therefore points the way to a future where AD can be treated, bringing benefit to millions of people.”
Prof Robert Howard, Professor of Old Age Psychiatry, UCL Division of Psychiatry, UCL, said:
“The MHRA has decided that the benefits of treatment with lecanemab outweigh the associated risks. The unusually long time that they have spent considering the drug suggests that this has not been an easy or straightforward decision.
“NICE’s decision, that the small benefits of treatment with lecanemab do not justify the associated financial costs for the NHS, should not come as a surprise. The absolute size of the difference between people treated for 18 months with lecanemab or placebo is about half of what has conventionally been considered to represent a clinicaly meaningful or noticeable effect. That is to say, in the theoretical example of a patient who could be assessed after 18 months of treatment with lecanemab or placebo, a trained assessor would not be able to detect any difference between the two situations.
“Although it has been claimed that drugs in this class slow the course of Alzheimer’s disease and that benefits may grow with time, the clinical trials were not designed to detect a change in the clinical course of dementia. It is just as possible that the drugs improve symptoms slightly and temporarily by removing amyloid but that the deterioration of dementia continues just as rapidly in the medium to long term.
“NICE’s statement does not represent a final decision but the beginning of a period of consultation and the provision of further information. I hope that the discussions and debate that will now follow can be informed by data and realistic appraisal of what we can expect from lecanemab. This new class of Alzheimer’s drugs caused enormous excitement because we have waited decades for new approaches to the treatment of a dreaded and common condition. However, there has been unhelpful exaggeration about what the new drugs can do and it has been difficult for patients and families to work out whether they should do everything they can to gain access to treatment or if this is just another false dawn in the search for effective treatment.
“Staff who work in dementia diagnosis and treatment services in the NHS will welcome the clarity of today’s statement from NICE. Our services would have needed to completely change in order to deliver these new treatments safely to a relatively small proportion of people with dementia. This would have entailed diversion of funding and trained staff from existing dementia services and I believe colleagues will be relieved to know that they are now unlikely to have to make the difficult decisions involved.
“For patients and families who may be disappointed and even angry about today’s announcement, I would say that those of us who work in NHS services for people with dementia would want to be sure that any new treatment was more likely to help than hurt them and that it wouldn’t damage our ability to provide the very best of evidence-based services to all of our patients.”
Prof Siddharthan Chandran, Director of the UK Dementia Research Institute, said:
“Today’s approval of lecanemab by MHRA marks a significant milestone in Alzheimer’s research, demonstrating for the first time that we can modify the disease course and slow cognitive decline. However, NICE’s initial recommendation that the benefits are too small to justify NHS use highlights the challenges we face in making these breakthrough treatments better and more widely accessible. NICE will be in consultation until final decisions later in the year.
“This situation underscores the urgent need for more affordable and rapid diagnostic tools, as well as a broader range of treatment options. At the UK Dementia Research Institute, we’re making substantial progress on these fronts.
“Multiple Sclerosis was considered untreatable just two decades ago, but an early class of drugs served as a catalyst for investment and today there are more than a dozen effective treatments available. At the UK Dementia Research Institute, we are poised to capitalise on a similar momentum in Alzheimer’s research. Our research programmes are exploring innovative approaches to diagnosis and treatment, aiming to develop solutions that are both effective and accessible within the NHS framework. We’re also collaborating with the Dementia Mission to increase clinical trials in the UK, working towards personalised treatment strategies.
“Today’s news reinforces our commitment to advancing research that can truly benefit all patients. We’re closer than ever to making effective Alzheimer’s treatments a reality for everyone who needs them.”
Dr Sebastian Walsh, NIHR Doctoral Fellow, University of Cambridge, said:
“It may seem confusing that the MHRA have granted a license but NICE have rejected lecanemab. But this is consistent with their roles in the system.
“The MHRA are the regulator, they look at evidence on whether the drug works and whether it is safe. The 18-month long trials showed lecanemab to be good at clearing the amyloid protein, and those taking the drug declined a little less than those on placebo during the 18 months. The MHRA weighed this evidence against the side effects, and decided it was sufficient to grant a license for certain groups of patients.
“NICE have a different job. They consider whether the drug offers good value for money for the NHS. This is because any money and resources (e.g. brain scans, staff time) spent on this drug are not available to be used for other things, meaning other NHS patients miss out. Lecanemab is expensive (tens of thousands per person per year in the US), and requires fortnightly infusions in specialist centres with trained staff. Moreover, working out who is and isn’t eligible requires a lot of testing, including genetic testing and brain scans. The majority of people with Alzheimer’s wouldn’t be eligible for these treatments. So it is unsurprising that NICE does not consider these drugs cost-effective and recommend against use in the NHS.
“Patients and their families will be understandably disappointed by NICE’s decision, especially after reading headlines about a “wonder drug”. But this is a really fast-moving field and it will be important to keep these decisions under review. As we find out more about longer-term effects, new ways of working out who may benefit and who won’t, new ways of giving the drugs, new drugs altogether, and the side effects, these risk-benefit (MHRA) and cost-effectiveness (NICE) equations may shift. We also must keep researching other ways of tackling dementia, beyond the amyloid protein, including prevention, good quality care, and reducing inequalities.”
Prof Sir John Hardy, Group Leader at the UK Dementia Research Institute at UCL, said:
“For decades this has been an ongoing aim of research. It started here in the UK nearly 40 years ago when we found a family with amyloid mutations. Now at last we have amyloid therapies, and they work. This is why patients gave us their blood samples and participated in research. This is the long-term outcome of their sacrifice.
“I’m disappointed however that NICE has not approved the drug for use in the NHS. This now puts us in a very difficult position where access to treatments will be limited. It’s especially disappointing because the research to develop these drugs started in the UK, and patients here gave us their blood samples and made sacrifices to participate.
“I’m hopeful that as we discover more about the lecanemab with ongoing research, and make progress on affordable, scalable diagnostic tools, this decision might be reconsidered. At the same time, we are working hard to find better drugs – drugs that are more effective, drugs that you can take as pills, drugs that target different processes in the brain. There are many programmes looking at this right now and we’re already seeing promising results.”
“This is a fast developing situation and I note that NICE wish to see more real world data on lecanemab use (from clinical practices not just clinical trials). That data is being gathered now and will, I suspect be published soon. At that point, the MHRA may feel confident enough to remove the restrictions on apoe4 homozygotes and NICE may reconsider their NHS funding restrictions. Here in the UK we need to focus on preparing the NHS to effectively use these drugs.”
Prof Tara Spires Jones, Group Leader at the UK Dementia Research Institute at the University of Edinburgh, President of the British Neuroscience Association, and Director of the Centre for Discovery Brain Sciences at the University of Edinburgh, said:“The MHRA’s decision to approve lecanemab for use in the UK is a fantastic example of decades of fundamental work in neuroscience leading to treatments that make a difference in people’s lives. Despite the understandable complexities of the decision to justify the cost to the NHS, it is disappointing that NICE has deemed the benefits of the drug too small to justify the cost.
“This will see greater inequities emerging in people with dementia, as only those who are able to access private healthcare will be able to receive the drug. It also underlines the need for us to double down on our research efforts to find new, affordable diagnostic tools that the NHS can deliver at scale, and different treatment options that can be implemented more easily in our health system. As researchers, there is plenty more to do in our search for drugs to treat Alzheimer’s and other related neurodegenerative conditions. But this is an important step on that journey.”
Dr Ivan Koychev, Senior Clinical Researcher, Dementia Platform UK, University of Oxford, said:
“The approval of lecanamab by MHRA is a milestone in the treatment of Alzheimer’s disease in the UK as it is the first such therapy that has been shown to affect core Alzheimer’s disease pathology. Currently approved treatments in contrast only affect symptoms without changing the underlying disease. The MHRA’s decision concludes that the benefit for cognitive (memory and thinking) and functional abilities outweighs the risk of brain bleeds. This is the case for people with one or no versions of the Alzheimer’s disease risk gene APOE4; in those with two versions of this gene, the risk of brain bleeds is higher which led MHRA not to approve it in that group. In contrast, NICE looks at whether MHRA approved medications are good value for money in the NHS. To do this, it examines so-called quality-adjusted life years (QALYs) which look at how much a new intervention such as lecanamab benefits a patient in terms of quality of life gained relative to their expected years of life. This is done so that the NHS can have a shared benchmark for new interventions across disease areas and patient groups – this is critical in the resource constrained NHS. NICE found that lecanamab did not represent sufficiently good value for money as it stands. What follows is a period of further consultation with stakeholders and the company; a potential outcome may be that a revised, more acceptable, cost structure is put forward to NICE. Should NICE not eventually recommend lecanamab or similar therapies, access to these novel treatments will only be available through the private sector in the UK which would raise the issue of equality of access.”
Hilary Evans-Newton, Chief Executive at Alzheimer’s Research UK, said:
“Today’s news is bittersweet for people affected by Alzheimer’s disease. It’s a remarkable achievement that science is now delivering licensed treatments that can slow down the devastating effects of Alzheimer’s, rather than just alleviating its symptoms. However, it’s clear our health system isn’t ready to embrace this new wave of Alzheimer’s drugs. It means that, as things stand, people in the early stages of the disease will be denied access to lecanemab through the NHS, and it will only be available to those who can pay privately. This is deeply disappointing.
“Of course, like first-generation treatments for other diseases, lecanemab has modest benefits and side effects that need careful monitoring. It’s not a cure, but it is a real step forward – the first new dementia medicine to be licensed in more than 20 years.
“Further negotiations between NICE, Eisai and the NHS may offer a way forward. But the heartbreaking reality is that those who could benefit from drugs like lecanemab don’t have time to wait. We’ve written to the Health Secretary Wes Streeting urging him to act, and to find a solution so that people with dementia in the UK don’t continue to miss out on innovative treatments. As well as considering how to make drugs like lecanemab available, there also needs to be a real focus on improving the way dementia is diagnosed within the NHS. The shocking reality is that one in three people in England with dementia never get a formal diagnosis, leaving them unable to access the care and support they need.
“Lecanemab represents the beginning of a sea-change in how diseases like Alzheimer’s will be treated in future. There are now more than 160 trials underway testing over 125 experimental treatments for Alzheimer’s across the globe, including 30 in late-stage trials. Despite today’s frustrating news, it really is a matter of when, not if, new treatments become available.
“What people living with Alzheimer’s disease – and other forms of dementia – desperately need are new medicines that improve their lives and Alzheimer’s Research UK will work tirelessly on behalf of people affected by dementia to ensure they get them.”
Declared interests
Dr Liz Coulthard: I was one of the two clinical experts on the NICE Technology Appraisal, and I was paid by Eisai to attend an MHRA hearing on lecanemab. I have also been paid by Eisai, Lilly and Biogen for consultancy and production of educational materials.
Prof John Gallacher: No direct interest in the decision or its consideration.
Prof Bart De Strooper: “I have been consultant and advisor for many pharmaceutical companies, including EISAI, and I have been founder of two spin off companies (Augustine TX and Muna TX).”
Prof Paul Morgan: “I have no conflicts to report.”
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 Dementia Research Institute, and am the National Specialty Lead for Dementia and Neurodegeneration in the NIHR Research Delivery Network. I have sat on two NHS England policy working groups looking at diagnostic pathways and delivery issues relating to lecanemab treatment for Alzheimer’s Disease. I practise clinically at Imperial College Healthcare NHS Trust and also carry out a fortnightly private clinic at Cleveland Clinic London.”
Prof Andrew Doig: “Andrew Doig is a Professor of Biochemistry at the University of Manchester. He is a founder and director of PharmaKure, a spin-out company working on diagnostics and drugs for Alzheimer’s Disease and other neurodegenerative conditions.”
Prof Robert Howard: “No relevant COIs.”
Prof Siddharthan Chandran: “Siddharthan is the academic lead of Neurii, a £5M partnership to deliver patient focused digital health solutions for dementia, part funded by Eisai.”
Dr Sebastian Walsh: “No conflicts of interest.”
Prof Sir John Hardy: “John has consulted for Eisai and Lilly.”
Prof Tara Spires Jones: “I did consult for Eisai in 2022 on a small project making a virtual reality representation of the brain changes in Alzheimer’s disease, and I was paid just under £3000 pounds for the consulting. This was an educational project, unrelated to lecanemab. I do not have any involvement with lecanemab or any ongoing roles with Eisai or Biogen.”
Dr Ivan Koychev: “Ivan Koychev has received a grant and speaker fees from Novo Nordisk. He is a paid medical advisor for digital healthcare (Five Lives SAS, Cognes, Cognetivity, Lola Speaks, Your Patient Choice) and biotechnology (CFDX Ltd) companies in the dementia space; he has a private neuropsychiatric practice through Brain and Mind Ltd. Ivan Koychev is a former NICE Committee D member but did not take part in the lecanamab decision making on account of above conflicts of interest.”
Hilary Evans-Newton: “Nothing to declare.”
For all other experts, no reply to our request for DOIs was received.