Lecanemab is the first treatment of Alzheimer’s disease licensed for use in Great Britain that shows some evidence of efficacy in slowing progression of the disease.

A large-scale trial in 2022, involving 1,795 volunteers with early-stage Alzheimer’s, found that Lecanemab was able to slow cognitive decline by 27% over the course of 18 months of treatment. It also slowed down the decline in quality of life by up to 56%.

Lecanemab was fully approved by the US Food and Drug Administration (FDA) as a treatment for early Alzheimer’s disease in July 2023.

The decision from the MHRA today follows an application from Eisai (who make Lecanemab), made in May 2023. The approval was given as a result of expert scientific advice on the benefit risk of Lecanemab from the Commission on Human Medicines (CHM), the government’s independent advisory body.

However, the National Institute for Health and Care Excellence (NICE) – who decide whether drugs should be made available on the NHS – have published draft guidance today, advising that the benefits of Lecanemab are too small to justify the cost to the NHS.

The decision will be reviewed following a public consultation and a second independent committee meeting later this year.

Director of the Dementia Research Centre, UCL Queen Square Institute of Neurology, and Group Leader at the UK Dementia Research Institute at UCL, Professor Nick Fox said: “This is a momentous occasion. The MHRA approving Lecanemab brings us closer to providing a therapy that slows the progression of Alzheimer’s for the first time. This will be a great source of hope to people living with Alzheimer’s and their families. 
“However, the next hurdle is approval by NICE. It would further increase current inequities if this was only available to those who could pay privately.
“The NHS will face huge challenges in delivering the drug. At the moment, it is typically three years between symptom onset and clinical diagnosis. We need to ensure that diagnosis happens earlier - early enough for people to still be eligible for treatment with Lecanemab. Additionally, when given the drug, people need careful monitoring via MRI scans, and the NHS lacks capacity to offer these at scale. I support Alzheimer’s Society who are calling on the government to make dementia a priority.
“We need to improve access to biomarker testing and brain imaging. The UK Dementia Research Institute are developing blood biomarker testing which could revolutionise the diagnosis of Alzheimer’s. In addition, UK DRI researchers are accelerating MRI scans so that they can be done in a shorter time to allow more people to benefit from this scarce resource that will be critical to ensuring the drug is delivered safely.”

Lecanemab works by targeting beta amyloid – a plaque that builds up in the brains of people with Alzheimer’s disease.

This was an idea pioneered by Professor Sir John Hardy when he began researching genetic Alzheimer’s Disease alongside Professor Martin Rossor (both UCL Queen Square Institute of Neurology).

After working with the Jennings family*, Professor Hardy discovered that a mutation to the amyloid precursor protein (APP) gene, creates the amyloid plaques that form in the brain during Alzheimer’s disease.

Amyloid affects brain cells by causing them to become overactive and signalling for ongoing inflammation, which can disrupt normal processes in the brain.

Blood flow can also be affected and other proteins in the brain can become involved. For example, when too much amyloid is deposited, it can react with another toxic protein called tau, which causes neuronal death.

In those with genetic Alzheimer’s this happens early because the patient makes too much APP. However, it also happens in those with non-genetic Alzheimer’s but at a slower rate.

As a result of these findings, in 1992, Professor Hardy and his colleague Professor David Allsop published the amyloid cascade hypothesis, which they hoped would “facilitate rational design of drugs to intervene in this process.”

The theory helped to explain the three key features seen in the brains of people with Alzheimer’s disease, including the brain appearing smaller due to the death of brain cells, the build-up of amyloid protein and tangles with tau.

Over the years, the amyloid cascade hypothesis was built upon, modified, and challenged by researchers. However, the development of anti-amyloid drugs continually proved to be difficult.

For example, only last month, the European Medicines Agency rejected approval for Lecanemab amid debate over its efficacy and safety.

Consequently, today’s MHRA decision has been hailed as “momentous” by dementia researchers.

Professor Sir John Hardy 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.
“The major challenge now will be to get much better at diagnosis. We are making good progress in both genetics and fluid biomarkers, but there is still much work to do to improve our predictions of risk in non-white populations. Implementing new diagnostic tools will also be a huge challenge organisationally for the NHS.
“I really believe that this is just the beginning. If we can get better at early diagnosis, we will stop the disease more effectively, and there’s good reason to think we’ll also reduce those worrying side effects. That’s what will bring the quickest improvement for people.”

UCL has continued to be at the forefront of trialling the efficacy of new drugs, such as Lecanemab.

And Professor Cath Mummery, who is Head of Clinical Trials at the Dementia Research Centre, UCL Queen Square Institute of Neurology, is the UK lead for a trial of Lecanemab in combination with an anti-tau immunotherapy in genetic Alzheimer’s disease, aiming to prevent symptom onset in this group.

It is hoped that the results will inform future use of Lecanemab and other therapies, not just in this group but in the wider Alzheimer’s population.

Links

* The Jennings vs Alzheimer’s: Shaping a new “treatment era” through discovery