New Alzheimer’s treatment, lecanemab, makes the headlines: what’s next?

This blog was edited on 6th January 2023 in response to the US Food and Drug Administration’s decision to approve lecanemab.

In November 2022, pharmaceutical company Eisai released the full results of a trial of a new Alzheimer’s treatment called lecanemab.

These results have been hailed as momentous by many dementia researchers, as the drug appears to be the very first that works by tackling the disease itself, rather than only treating its symptoms. We are now waiting to hear from regulatory organisations about whether lecanemab will reach patients, including in the UK.

If lecanemab is approved by the regulators that govern the UK, it would be the first new Alzheimer’s drug here for nearly 20 years.

At Alzheimer’s Research UK, we are dedicated to making life-changing breakthroughs in the treatment, diagnosis, prevention and cure of dementia. We know that this news is of huge interest to those affected by dementia, as well as the research community. That is why we’ve brought together some of the questions you asked our Dementia Research Infoline and across our social media channels.

How does lecanemab work?

Lecanemab is a type of drug called a monoclonal antibody. Antibodies form part of our immune system and bind to harmful proteins to destroy them. Lecanemab contains antibodies which bind to a protein called amyloid, which builds up in the brains of people with Alzheimer’s. Although our bodies naturally produce antibodies, the specific anti-amyloid antibodies used in this treatment are created in a lab. They are delivered via an infusion, which involves spending several hours in a clinic every two weeks.

Scientists have long suspected that clearing amyloid from the brains of people with dementia will slow down the disease, and so allow people with dementia to live independently and with milder symptoms for longer.

Is lecanemab effective?

Lecanemab was tested in a trial called CLARITY AD, which was a ‘phase 3’ trial – this is generally the final stage of testing a drug goes through (see diagram).  During the trial, around 900 people with early Alzheimer’s took lecanemab for 18 months, and a similar group of 900 people took a dummy drug (placebo).

 

The CLARITY AD results showed that lecanemab slowed the rate of decline in people’s memory and thinking over 18 months, and also slowed down the rate of decline in people’s ability to carry out day-to-day activities. In addition to this, people taking lecanemab saw a sharp reduction in amyloid levels in their brain, as measured by brain scans.

Lecanemab is the first treatment for any type of dementia to both reverse physical changes in people’s brain and also to slow decline in their memory and thinking.

When looking at what the results could mean for people living with dementia, lecanemab could slow down dementia progression, which could allow people with dementia to live independently for longer. However, more research is needed to confirm this, as the trial has so far only followed people for 18 months.

Will this drug work on other types of dementia, such as vascular dementia or dementia with Lewy bodies?

Lecanemab targets amyloid, which scientists believe to play an important role in the development of Alzheimer’s. It is not thought to be as important in other types of dementia, so it is unlikely to work against other diseases that cause dementia.

Beyond lecanemab, there are over a hundred drugs in clinical trials across the world investigating treatments for all types of dementia. At Alzheimer’s Research UK, we believe it is a question of when, not if, treatments for other types of dementia will become available.

At what stage of diagnosis could lecanemab be given?

Lecanemab has been designed for people in the early stages of Alzheimer’s disease. People included in the trials of this drug had mild cognitive impairment or mild Alzheimer’s disease, confirmed by a test of their spinal fluid or a PET brain scan showing a build-up of amyloid in their brain. Many experts suspect it would be unlikely to work in later stages of the disease, although this hasn’t been tested in trials yet.

How many people would be eligible for lecanemab?

Current statistics suggest that roughly one in three people with Alzheimer’s and one in five people with mild cognitive impairment (MCI) test positive for amyloid in the brain so could be eligible for treatment with a drug like lecanemab. Amyloid testing needs to become more widely available so that doctors are able to tell who in the UK with a diagnosis of MCI or Alzheimer’s is eligible for treatment and improve earlier diagnosis. This would result in an estimated 500,000 people being eligible to receive the treatment.

How safe is lecanemab?

There is concern about the impact of a side effect called ARIA (which stands for ‘amyloid related imaging abnormalities’). These are changes to brain structure and swelling seen on MRI brain scans.

Roughly 1 in 8 people who received lecanemab were found to develop ARIA, while less than 1 in 50 developed it among those who took the placebo (dummy) drug. However most (80%) of the people who developed ARIA did not have symptoms, and overall, less than 1 in 30 had any symptoms like as headaches or confusion.

Nevertheless, ARIA is poorly understood – including whether it can become more serious over time. So, the risk associated with lecanemab is something which is being closely monitored in longer-term studies and will be taken account by regulators when they decide whether to approve the drug.

How is this drug different to the ones we already have?

Current drugs like donepezil (Aricept) and memantine (Ebixa or Axura) are known as ‘symptomatic’ treatments – they allow our brain cells to communicate better so can counteract the damage caused by diseases like Alzheimer’s, but don’t target the underlying disease itself.  Although these treatments can make a big difference to somebody’s quality of life, they can’t slow or stop the underlying damage getting worse, and their benefits usually only last for around a year. By directly targeting amyloid, lecanemab slows down the disease, and will hopefully allow people to live independently for longer.

Find out more about treatments for Alzheimer’s disease that are currently available.

How is lecanemab different to other drugs that target amyloid, like aducanumab?

In a direct comparison to the anti-amyloid antibodies aducanumab and gantenerumab, lecanemab was reported to bind most strongly to the most toxic form of small soluble clumps of amyloid protein, while others attach to the larger, hardened amyloid plaques. It is still not clear why this makes lecanemab more successful.

Lecanemab also appears to remove amyloid much more quickly than either aducanumab or gantenerumab. Some experts think that this is why the trial of lecanemab was successful. In clinical trials lecanemab also showed lower incidence of ARIA than aducanumab.

Is lecanemab available in the USA?

The US Food and Drug Administration (FDA) granted a licence to Eisai to allow it to market lecanemab to people with a confirmed diagnosis of mild cognitive impairment (MCI) or early-stage Alzheimer’s disease in the US on January 6th, 2023. This means that US doctors can prescribe lecanemab to people with appropriate medical insurance, or who can afford to pay for it directly. However, both private and state medical insurers will need to decide whether they will cover the drug. Ultimately, this will determine who is able to access it in the US.

The FDA’s decision, made via its Accelerated Approval Programme, was based on reviewing the Phase 2 data that looked at lecanemab’s effect on amyloid removal in the brain. Since applying via the Accelerated Approval Programme last year, Eisai has announced further results from a randomised Phase 3 trial which have formed the basis of an application to the FDA for an approval of lecanemab through the agency’s regular process. You may have read about these results in the news last year.

If the Phase 3 data does not confirm lecanemab’s benefits, the FDA has regulatory procedures in place that could lead to removing the drug from the market.

Does ARUK support people travelling to the US to access lecanemab?

The health systems in the US and UK work very differently, and if people are to travel to the US to try to access treatment it would be at great personal cost. Although we realise the people with Alzheimer’s and their families in the UK are eager for effective new treatments, it’s important that the UK regulator carries out its own rigorous, independent assessment of Eisai’s data. We are urging for this to happen as quickly as possible without compromising the quality of the evaluation.

Will it be available on the NHS?

To be able to sell a drug in a particular country, a drug’s manufacturer needs to apply for a license. Eisai has submitted the data from its trial of lecanemab to the U.S. Food and Drug Administration, the European Medicines Agency, the UK Medicines and Healthcare products Regulatory Agency and other international regulatory bodies, so they can properly scrutinise it and decide whether to give it a license. If they do, it will be the first drug licenced in the UK which slows down the progression of Alzheimer’s.

To become available on the NHS, licensed drugs then need to be assessed by the National Institute for Health and Care Excellence (NICE) in England and Wales, and the Scottish Medicines Consortium in Scotland, who would decide whether the treatment is cost-effective for NHS use.

We are not yet sure when we can expect these decisions, but it is likely to be at least a couple of years before a treatment is available on the NHS.

As well as licensing and approval by organisations like NICE and Scottish Medicines Committee, the NHS itself will need to undergo significant changes in order to deliver a drug like lecanemab, such as infusion clinics in which to give the treatment to patients, and the ability to do PET scans or lumbar punctures for each patient to make sure they’re eligible for the drug. It is important to note that lecanemab requires infusions every two weeks – meaning that people would need to get to a hospital or specialist centre every other week to receive treatment. They would also need to have had a PET scan or lumbar puncture to confirm they were amyloid positive. While taking the drug, they will likely need regular monitoring for side effects like ARIA, which involves MRI scans too.

Given the large number of people who may be eligible for lecanemab in the UK, this is likely to be very expensive and require a large amount of resource. This will all need factoring into the decision and it’s likely this will not be a straightforward and quick process. Alzheimer’s Research UK will work with NICE and the Scottish Medicines Consortium to discuss these concerns and highlight ways forward that ensure patients don’t need to wait any longer than necessary to benefit from any new drug.

Alzheimer’s Research UK has written to Eisai, calling on them to put their data on lecanemab forward to the UK regulator without delay. We want Eisai to work with the UK government, the MHRA and the NHS to ensure an evidence-based decision on lecanemab’s safety and efficacy can be made as a matter of urgency.

How can I find out about taking part in research?

The best way to find out about taking part in dementia research studies is through a nationwide register called Join Dementia Research. When you register, you provide some personal details about your health, age and contact details. These details are then used to match you to studies that you are suitable to take part in.

Research studies are done online and face-to-face. Once registered, you can log into your account to take part in online studies, and you will be contacted by a researcher if you’re eligible to take part in a face-to-face study.

Join Dementia Research is not a research study itself but a place to find out what studies you can take part in and enrol to take part. Signing up to the register is not a commitment to take part in any particular study, it just allows research studies to find willing volunteers.

You find out more and register to Join Dementia Research online, or by calling the Dementia Research Infoline on 0300 111 5 111 (9-5pm Monday to Friday). The registration process takes 10-15 minutes over the phone.