By Siân Gregory
There are 141 drugs being tested in clinical trials for the treatment of Alzheimer’s disease. 78% of these drugs are designed to try and slow down how quickly the disease progresses. We examine the three most promising drugs, Donanemab, Lecanemab and Remternetug and summarise their journeys so far.
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.
Alzheimer’s disease causes the cells in the brain to get sick and eventually die, which leads to symptoms like memory loss.
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 topline results from its clinical trial. The drug is given to patients by an intravenous drip, which uses a liquid medicine in a bag and enters a person’s bloodstream through a catheter.
What’s the latest development with Donanemab?
Eli Lilly, the pharmaceutical company that developed Donanemab, has just announced the first topline results from the final stage (phase 3) clinical trial of Donanemab called TRAILBLAZER-ALZ 2. The trial included 1,182 people who have amyloid in their brains and symptoms of memory and thinking problems.
The trial showed that Donanemab can slow down how quickly memory and thinking skills get worse by 36% in people living with early Alzheimer’s disease.
Promisingly, the trial also demonstrated a 40% slowing in decline of everyday activities such as driving, doing hobbies, and managing finances. Donanemab successfully removed amyloid from the brains of more than 70% of participants in the 18 months of the trial.
Following the positive results, the company that makes Donanemab are likely to apply the Medicines and Healthcare Products Regulatory Agency (MHRA) for the approval of Donanemab in the UK. If approved, it will then be reviewed by the National Institute for Health and Care Excellence (NICE). Donanemab would need to be approved by both the MHRA and NICE before becoming available in the UK through the National Health Service (NHS).
2.Lecanemab and Alzheimer’s disease
What is Lecanemab?
Lecanemab (marketed under the name Leqembi) is another immunotherapy drug, developed by the pharmaceutical company Eisai. It is designed for people living with early-stage Alzheimer’s disease and is given to patients by an intravenous drip.
It has already been shown to be effective at slowing the progression of Alzheimer’s disease, and has already been approved in the US, with decisions by the EU and UK regulators due in 2024.
What’s the latest development with Lecanemab?
Lecanemab was approved by the US Food and Drug Administration (FDA) as a treatment for early Alzheimer’s disease in January 2023. This means that it can now be given to patients with early Alzheimer’s disease in the USA. It was also announced that the drug will be marketed under the name Leqembi and that an application had been made to the European Medicines Agency for approval in the EU.
Before the announcement of Lecanemab’s approval, the full results from a final (3rd) stage clinical trial on Lecanemab, called ClarityAD, were released at the Clinical Trials on Alzheimer’s Disease conference on 29th November 2022.
The results showed that Lecanemab successfully removed amyloid and tau proteins from the brains of people living with early Alzheimer’s disease.
For the people taking Lecanemab, this meant that the decline in their thinking and memory skills was slowed down by 27%. It also slowed down the decline in quality of life by up to 56%.
These exciting results could be game-changing. They give us hope that in the future, people with early Alzheimer’s disease could have more time with their loved ones.
Where could Lecanemab become available?
Before Lecanemab can become available for use it will have to be approved as a safe and effective treatment by drug regulatory bodies.
United States of America
After approval by the FDA in January 2023, it can now be given to patients with early Alzheimer’s disease in the USA. However, this does not affect whether Lecanemab will be available in other countries.
Europe
The drug company submitted an application to the European Medicines Agency (EMA) for approval of Lecanemab in the EU. We expect the EMA to make a recommendation to the European Commission on whether Lecanemab should be approved for use in Europe in the first half of 2024.
United Kingdom
For Lecanemab to be available in the UK, it would have to be approved by the Medicines and Healthcare Products Regulatory Agency (MHRA) in the UK. Following Brexit, the Government has stated that the MHRA will follow decisions made by the European Commission until January 2024. We do not yet know whether Lecanemab will be approved for use in the UK.
3.Remternetug and Alzheimer’s disease
What is Remternetug?
Remternetug is the third of these promising amyloid targeting immunotherapy drugs and is also made by Eli Lilly, who makes 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 effects 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 a 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 began in July 2020 to test 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 than 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.
What does this mean for people living with Alzheimer’s disease in the UK?
It is an incredibly exciting and hopeful time for dementia research, with both Lecanemab and Donanemab proving that Alzheimer’s disease can be slowed by targeting amyloid.
These trials will teach us a great deal about the benefits of removing amyloid protein from the brain using immunotherapies.
For any drug to become available in the UK, it must be approved by the MHRA. The MHRA scrutinise the clinical trial data of every drug and uses this data to determine whether the drug is safe and effective as a treatment.
Beginning of the end of Alzheimer’s disease?
This could be the beginning of the end of Alzheimer’s disease.
Lecanemab and Donanemab represent the exciting first steps in our journey to develop new treatments to slow down and stop the diseases that cause dementia. More research will improve upon these drugs to make better treatments to slow down or stop Alzheimer’s disease in its tracks.
But that’s not all. There are many different diseases of the brain that cause dementia, with each disease affecting brain cells in different ways.
It is crucial that research continues 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.
source: alzheimers.org.uk
Download the full issue of the July-August 2023 Healthy Options News Digest here.
