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 cells in the brain to get sick and eventually die, which leads to symptoms like memory loss.

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

Recently lecanemab, marketed under the trade name Leqembi, was the first disease-modifying treatment approved for use in the UK for Alzheimer’s disease. This was followed by donanemab, marketed as Kisunla, which was also approved by the Medicines and Healthcare Products Regulatory Agency (MHRA).

These two drugs are now approved for use in the UK. However, they are not recommended for use on the NHS at this stage.    

Other drugs are available which manage 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. 

Clinical trials for Alzheimer’s disease

Before a drug can be approved for use in any country, it must be shown to be safe and effective. To do this, drug companies run rounds (or phases) of clinical trials to show how well a drug works and how safe it is.  

• Phase 1:  This initial phase involves a small group of volunteers and aims to assess the drug's safety and appropriate dosage.
• Phase 2:  A larger group of participants, usually numbering in the hundreds, are involved in Phase 2 trials. This phase focuses on evaluating the drug's effectiveness, whilst continuing to monitor safety.
• Phase 3: These large-scale trials often include hundreds or thousands of participants and are designed to confirm the drug's efficacy and safety in a diverse population.

If the phase 3 trials are successful, the results are passed onto regulators, like the MHRA, who decide whether the drug should be approved for use.

Here we explore three drugs in phase 3 trials that have shown promise as treatments for Alzheimer’s disease.  

1. Remternetug and Alzheimer's disease

What is remternetug?

Remternetug is the next promising drug to come down the pipeline. Like lecanemab and donanemab before it, remternetug targets amyloid, a protein that builds up in the brain of some people with dementia. It is also made by Eli Lilly, who makes donanemab. It is 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 over the course of an hour. The trial of remternetug compares this method with injections under the skin. It is hoped that an injectable version will prove to be more effective and reduce the adverse effects seen with the other immunotherapy drugs. It also provides a more practical way of taking the drug - similar to insulin pens used for diabetes.   

What’s the latest development with remternetug?

After initial safety tests, Eli Lilly began a larger-scale phase 3 trial of remternetug (called TRAILRUNNER-ALZ 1). This was set up 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 finished collecting the data for its primary endpoint (the percentage of patients who had amyloid cleared), and the full 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 than donanemab. 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.  

2. Buntanetap and Alzheimer's disease

What is buntanetap?

Buntanetap is a new drug being investigated as a potential treatment for Alzheimer's disease. It primarily targets the amyloid protein, a key component of the plaques that form in the brains of people with Alzheimer's. It reduces the production of amyloid precursor protein (APP), which is processed into the toxic form of amyloid. In this way buntanetap aims to slow down or prevent the progression of the disease.  

What’s the latest development with buntanetap?

A recent trial has shown positive outcomes in participants with early-stage Alzheimer's disease. The trial showed significant improvements in memory and thinking scores after 12 weeks of treatment with buntanetap. Additionally, the drug was found to reduce levels of the tau protein in the blood, another key factor in Alzheimer's disease. Importantly, buntanetap treatment did not lead to any serious side effects.

Next Annovis Bio is planning to conduct a larger phase 3 study to confirm and expand on these findings. This 18-month trial will focus on individuals with early-stage Alzheimer's disease and will test whether buntanetap can help slow down the progression of Alzheimer’s disease. 

3. Semaglutide and Alzheimer's disease

What is semaglutide?

Semaglutide is a medication primarily known for its use in managing type 2 diabetes and, more recently, aiding in weight loss. It's sold as a pill and marketed under the brand names Ozempic and Wegovy. Research into people taking drugs like semaglutide for diabetes showed that they had a reduced risk of developing dementia. This led to clinical trials to test the potential role of semaglutide in helping to treat Alzheimer's disease.

Semaglutide works by mimicking a natural hormone in the body that stimulates insulin production and reduces blood sugar levels. Scientists believe that this mechanism might also be beneficial for the brain. By improving insulin sensitivity and potentially interacting with receptors involved in learning and brain cell protection, semaglutide could potentially slow the progression of Alzheimer's disease. 

What’s the latest development with semaglutide research?

Novo Nordisk, the pharmaceutical company behind semaglutide, is currently conducting multiple clinical trials to investigate its potential benefits for individuals with Alzheimer's disease.

One trial is focused on assessing the safety of semaglutide and its impact on gene expression in people with Alzheimer's. This study is nearing completion, with final results expected by September 2025.

Two other trials are examining whether semaglutide can improve memory and thinking abilities in individuals with Alzheimer's disease. One of these trials is specifically targeting people who also have conditions that affect the brain's blood vessels.

If these trials demonstrate promising results, semaglutide could represent a significant breakthrough in the treatment of Alzheimer's disease.

Who are these new drugs for?

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.   

Although they work differently remternetug and butanetap are both designed to target 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.  

Semaglutide targets insulin resistance in the brain. This means that it tries to restore how the brain balances the amount of sugar that is available to make energy. Although it is currently being tested for Alzheimer’s disease, insulin resistance may be a problem in other forms of dementia too.

Can these drugs be accessed in the UK now?

At this stage, all the drug treatments mentioned here are experimental medicines and are not available to patients in the UK outside of clinical trials. However, lecanemab and donanemab, two amyloid-targeting drugs, have been approved for use in the UK but have not been recommended for use through the NHS.

Before remternetug, butanetap and semaglutide can also become available in the UK, they must be approved by the Medicines and Healthcare Products Regulatory Agency (MHRA).

 The MHRA will make a decision as to whether or not to approve these drugs and make them available for use. These decisions will consider both the safety and the effectiveness of each drug.

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

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 needs to be recommended by the National Institute for Health and Care Excellence (NICE).  For this decision, NICE will take into account how cost-effective a treatment is.  Currently, lecanemab and donanemab were not considered cost-effective enough to be recommended for the NHS. However, we have hope that new drugs will be approved for use on the NHS in the future.

Many different brain diseases 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.