Here, UK DRI researchers respond to the news.
Prof Siddharthan Chandran, UK DRI Director, 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. The UK DRI is 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."
Prof Tara Spires-Jones, Group Leader at the UK DRI at 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.”
Prof Sir John Hardy, Group Leader at the UK DRI at UCL, and Chair of Molecular Biology of Neurological Disease at the UCL Queen Square Institute of Neurology, 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.”
Prof Paul Morgan, Interim Director, UK DRI at Cardiff, 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 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.”
Declared interests
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 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.”
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.”
Links
MHRA press release
NICE press release
Media coverage
BBC Breakfast
BBC Radio 4 Today - listen from 01:09:08
BBC Radio 5 Live - listen from 2:25:00
BBC Radio 5 Live - listen from 14:20
LBC
Guardian
Daily Mail
Sun
Article published: 22 August 2024
Banner image: Shutterstock/Fizkes
