Research

Three promising drugs for treating Alzheimer's disease bring fresh hope

What drugs are there for people living with Alzheimer's disease?

Alzheimer’s disease causes the cells in the brain to get sick and eventually die, which leads to symptoms like memory loss.

To treat Alzheimer's disease, we need to find effective drugs that are able to slow down or stop it. These drugs are often called ‘disease-modifying' treatments.

Recently  a drug called lecanemab that slows down memory and thinking decline has been approved to treat early Alzheimer’s disease by the Medicines and Healthcare products Regulatory Agency (MHRA).  

Lecanemab, marketed under the trade name Leqembi, is the first disease-modifying treatment available in the UK for any type of dementia, including Alzheimer’s disease. 

The UK is now among the latest country to approve lecanemab, following decisions in countries including US, Japan, and China.  However draft recommendations from the National Institute for Clinical Excellence do not recommend it for use on the NHS at this stage.   

Other available drugs only treat the symptoms of Alzheimer’s disease. They do not treat the root cause of the disease and so do not slow down how quickly it gets worse.

A new type of treatment

In the brains of people living with Alzheimer’s disease, a protein called amyloid builds up into plaques. These plaques are thought to be toxic and damage the cells of the brain. 

It was Alzheimer’s Society-funded research led by Sir Professor John Hardy that first showed the importance of amyloid protein’s role in the causes of Alzheimer’s disease over 30 years ago. 

Researchers have gone on to develop drugs which can clear amyloid from the brain. These drugs are called immunotherapies. They target the amyloid plaques in the brains of people with Alzheimer’s disease to try and help break them down.

Immunotherapies are already used in medicine, for example in the treatment of some cancers. 

Researchers believe that by clearing amyloid plaques from the brain they will be able to slow down how quickly Alzheimer’s disease gets worse.

Here we explore three drugs that work in this way and have shown promise as treatments for Alzheimer’s disease. 

1. Donanemab and Alzheimer's disease

What is donanemab?

Donanemab is the most recent of the immunotherapy drugs to make headlines with the release of the full results from the large final stage trial (called TRAILBLAZER-ALZ2). The trial included 1,182 people who have amyloid in their brains and symptoms of memory and thinking problems.  

Donanemab was developed by the pharmaceutical company Eli Lilly and is given to patients by an intravenous drip, which uses liquid medicine in a bag and enters a person’s blood through a cannula.  

What’s the latest development with donanemab?

Last year the UK government announced that from January 2024 the MHRA would give “rapid, often near-automatic sign-off for medicines and technologies already approved by trusted regulators in other parts of the world such as the United States, Europe and Japan.”

In July 2024  the FDA approved donanemab, so we are now awaiting a decision by the MHRA in the UK. . We don’t know if the MHRA and NICE will make the same decisions about donanemab as they have done with lecanemab. Differences in how safe and effective the drug is, as well as its cost-effectiveness mean that the decision will be independent of the decision about lecanemab.” 

In the main clinical trial for donanemab (called TRAILBLAZER-ALZ2), the drug worked better the earlier in the disease course it was given. It appeared to slow how fast memory and thinking get worse by 20-60%, depending on the memory test used and the amount of changes in the brain associated with Alzheimer’s disease that the participant had.  

The trial also demonstrated a 40% slowing in decline of everyday activities such as driving, doing hobbies and managing finances.

Several other trials are being conducted with donanemab. A trial called TRAILBLAZER-ALZ3 is exploring whether donanemab treatment can delay or prevent the development of Alzheimer’s disease.

Another trial called TRAILBLAZER-ALZ4 has compared donanemab treatment to that of another anti-amyloid drug called aducanumab, which is currently only approved for the treatment of Alzheimer’s disease in the United States. 
 

2. Remternetug and Alzheimer's disease

What is remternetug?

Remternetug is the third of these promising amyloid targetting immunotherapy drugs and is also made by Eli Lilly, who make donanemab. It is also for people living with early-stage Alzheimer’s disease and has been described as a second generation immunotherapy as it targets the same type of amyloid as donanemab, but is hoped to perform better. It is also being given to patients in a different way.

Other immunotherapies being developed for Alzheimer’s disease are given by an intravenous drip. This requires patients to attend sessions  in a clinic to receive their medicine and can take up to an hour. The trial of remternetug is comparing this method with injections under the skin. This is in the hopes that it is more effective and reduces the adverse affects seen with the other immunotherapy drugs. It also provides a more practical way of taking the drug – that is similar to insulin pens used for diabetes.  

What’s the latest development with remternetug?

In November 2018, Eli Lilly first tested remternetug in an small phase 1 trial, giving the drug to 36 healthy participants to check that it gets into the blood stream and whether it was safe. The results were not published, but a second exploratory trial was begun in July 2020 to test the the safety of remternetug on people living with mild-to-moderate Alzheimer’s disease. This trial is due to end in January 2024.

Overlapping with this trial, in August 2022, a larger scale phase 3 trial of remternetug (called TRAILRUNNER-ALZ 1) commenced. This is to test the effectiveness and safety of remternetug in a larger group of people with mild Alzheimer’s disease. They will also compare the two different methods of giving the drug. This trial is due to end in 2025.

Whilst the full results of remternetug trials won’t be released for a while, early data has suggested that remternetug may be better at clearing amyloid that donanemab is. This data showed that after 6 months of treatment 75% of 41 people tested had amyloid cleared from their brains. This is in contrast with donanemab which took 18 months to have 72% of patients cleared of amyloid. However there we also a number of cases of people who had swelling or bleeding in their brains due to taking remternetug.

3. Blarcamesine nd Alzheimer's disease

What is blarcamesine?

Blarcamesine is a drug for Alzheimer’s’ disease developed by Anavex Life Science Corp. It works in a different way to the other drugs we’ve heard about. It activates a receptor called sigma-1 that helps prevent proteins from misfolding. It is the misfolding of amyloid that leads to it forming clumps in the brains of people with Alzheimer’s disease.

It may also stop another protein called tau from misfolding and helps protect the part of the cell that creates energy – the mitochondria.

The drug is taken as a capsule, once a day, so patients wouldn’t require weekly, or fortnightly trips to a clinic for the medicine. 

What’s the latest development with blarcamesine?

In August 2024 at the Alzheimer’s Association Interational Conference, the company announced the results of their clinical trial. Participants on the drug had a slowing of decline of memeory and thinking abilites by more than 25%. Though no difference was seen in abilities to carry out every day tasks

The side effects were mostly mild or moderate, with a minority of patients having dizziness, confusion or a fall.  

The company has announced that they plan to apply for marketing approval in Europe at the end of 2024.

The drug is also being tested for other conditions, including Parkinson’s disease dementia. 

Who are these new drugs for?

Donanemab and remternetug are designed specifically to target and clear away amyloid – a toxic protein that builds up in the brains of people living with Alzheimer’s disease. This means that they would not have any benefit for someone living with another type of dementia, such as vascular dementia or frontotemporal dementia.  

Blarcamesine works more generally to help stop proteins from misfolding. As well as being tested for Alzheimer’s disease, it is also being tested for Parkinson’s disease dementia.

These new drugs are designed to treat people living with early-stage Alzheimer’s disease. Clinical trials have suggested that they have benefits for people who have either mild cognitive impairment (MCI) or early-stage Alzheimer’s disease. However, there isn’t any evidence to suggest that they are beneficial for people living in the later stages of Alzheimer’s disease.  

Can these drugs be accessed in the UK now?

At this stage, all the drug treatments mentioned in this blog are experimental medicines and are not available to patients in the UK outside of clinical trials. However lecanemab, another drug that targets amyloid, has been approved for use in the UK.

Before donanemab, remternetug or blarcamesine can become available for use in the UK, their associated pharmaceutical companies must apply to the Medicines and Healthcare Products Regulatory Agency (MHRA) for their approval.  This UK drug regulatory body will make a decision as to whether or not to approve these drugs and make them available for use. These decisions will take into account both the safety and the effectiveness of each drug.

Until these drugs have been approved by the MHRA, donanemab, remternetug and blarcamesine remain unavailable and cannot be prescribed to patients in the UK.  

We advise that no decisions around treatment for the diseases that cause dementia should be made without discussion with a GP or dementia specialist.  

Could a new Alzheimer's disease drug become available on the NHS?

For a drug to be available on the NHS, it would also need to be approved by the National Institute for Health and Care Excellence (NICE).

For this decision, NICE will take into account how cost-effective a treatment is.

This could be the beginning of the end of Alzheimer's disease.

Now that lecanemab has been approved in the UK, drugs like donanemab, remternetug and blarcamesine represent the next step in the journey to find better drugs to slow down and one day stop Alzheimer’s disease.

But that's not all. Many different diseases of the brain cause dementia, with each disease affecting brain cells in different ways. Research must continue to uncover what is going wrong inside the brain. With this knowledge, researchers will develop new, innovative treatments to tackle every type of dementia.

Alzheimer’s Society is committed to continue investing in the best researchers who will go on to develop improved, targeted treatments that will someday benefit everyone living with dementia. 

How can I be involved in dementia clinical trials?

Clinical trials testing drugs that are designed to slow down the progression of the diseases that cause dementia are being conducted around the world. However, few of these sites are in the UK. Also, most drugs in trials are designed to treat the disease as early as possible when a person has only mild symptoms, or even before they have symptoms at all.  

For anyone interested in taking part in dementia research, we would recommend registering their interest with Join Dementia Research. 

This article was first published in December 2020 and has been updated to reflect recent research progress. Please speak to your GP if you have questions specific to your situation.