Aducanumab is a drug that has been developed as a potential treatment for Alzheimer’s disease. Find out more about the drug, its path to approval in the US, and what it means for people with dementia in the UK.
Over 900,000 people are living with dementia in the UK and sadly there are no treatments that can slow down or stop it from progressing.
Research is providing hope. Today there are 125 drugs in clinical trials to treat Alzheimer’s disease - one of the main causes of dementia.
There are still major challenges in developing treatments. Unfortunately, many drug trials have not shown significant benefits for people with dementia. However in 2019, results from clinical trials testing a drug called Aducanumab showed some promise in slowing the progression of symptoms in people with early-stage Alzheimer’s disease.
In June 2021, the Food and Drugs Administration (FDA) - the drug regulatory body in the USA - approved Aducanumab for clinical use in people with Alzheimer’s disease in the USA.
The European Medicines Agency (EMA) has now reviewed the data and in December 2021 made the decision to refuse the licence for this drug in Europe stating that there was currently insufficient evidence that Aducanumab was safe, effective and had clinical benefit for people living with Alzheimer’s disease.
Aducanumab remains unavailable in Europe and the UK.
What is Aducanumab?
Aducanumab is an antibody therapy that targets amyloid beta protein. This protein accumulates in clumps in the brains of people with Alzheimer’s disease.
Researchers believe these clumps play a role in damaging brain cells, ultimately causing them to stop working and die. This gradually leads to the symptoms we see in people with Alzheimer’s disease, such as dementia.
Alzheimer’s Society funded work leading to the discovery of the first Alzheimer’s gene in 1991. This work, led by Professor John Hardy, provided the first piece of strong evidence that a build-up of amyloid in the brain may play a pivotal role in the development of Alzheimer’s disease and could the trigger the disease.
The “amyloid hypothesis” has hugely influenced Alzheimer’s disease research. Now, nearly 30% of current disease-modifying treatment in phase III trials – including Aducanumab – aim to prevent the disease through targeting amyloid.
What were the results of clinical trials using Aducanumab?
Early stage, smaller trials
After initial trials showed that Aducanumab was safe to use in humans, a further trial called PRIME assessed if the drug could slow the progression of Alzheimer’s disease in people who were in the early stages of the disease. This included people who had mild cognitive impairment (MCI) or early-stage dementia.
The PRIME trial started in 2012. Biogen, the pharmaceutical company who developed the drug, reported that treatment led to a reduction in amyloid levels in the brain. The company said the drug appeared to slow the rate of cognitive decline for people with mild Alzheimer’s disease receiving the drug.
Large and longer trials
These findings allowed Biogen to conduct larger clinical trials of Aducanumab. Two trials, called ENGAGE and EMERGE, collectively enrolled over 2,500 people with MCI or early-stage dementia caused by Alzheimer’s disease.
The changes in the brain caused by Alzheimer’s disease tend to start many years before symptoms show. This means that earlier treatment is likely to have a better chance of being effective. The main aim of the ENGAGE and EMERGE trials was to see if Aducanumab could reduce signs of cognitive decline in the people with MCI and mild dementia. Participants received different doses of the drug and were compared to people receiving a placebo treatment. The placebo contained no active ingredient.
The two large Aducanumab trials began in 2015 but were cut short in March 2019. Although the EMERGE trial was said to be ‘trending positive’ in terms of potential outcomes, early results indicated the ENGAGE study was not going to be successful. In order to progress, Biogen had specified that both trials needed to be heading in the right direction. The results meant that both trials were terminated.
However, further analysis using data from more participants changed Biogen’s initial conclusions. The EMERGE trial data showed a positive effect in people given Aducanumab compared to placebo. The ENGAGE trial however only demonstrated a clinical benefit in a subgroup of people on a higher dose of Aducanumab – only specifically in relation to memory and thinking skills. As a result, Biogen restarted enrolment of participants back into the clinical trials, which are now due to finish in 2022.
Both trials showed a reduction in the levels of amyloid beta in the brain of those treated.
The reanalysis of EMERGE and ENGAGE suggested some reduction in cognitive decline in people taking the higher dose of Aducanumab.
Are there any known side effects from Aducanumab?
From the clinical trials, the main side effect of Aducanumab treatment reported was amyloid-related imaging abnormalities (ARIA). These are thought to be micro-bleeds or swelling in the brain and have been reported in other anti-amyloid trials, particularly following high-dose treatment.
Biogen reported individuals with ARIA showed mild to moderate symptoms, with some displaying dizziness, headaches and nausea. These effects mean it will be important to continually monitor patients on undergoing Aducanumab treatment.
How has the research progressed for Aducanumab?
Biogen announced they would be submitting an application to the FDA to license Aducanumab.
The FDA brought together and publicly broadcast an independent advisory committee meeting to discuss the evidence. The advisory committee voted against the approval of Aducanumab as a treatment for people with early Alzheimer’s disease. The committee felt there was insufficient evidence to show it is effective.
The FDA reached their final decision and approved the drug for use as a treatment for people living with Alzheimer’s disease at any stage. This decision was largely made on the drug's ability to reduce amyloid in the brain. However, it is still unclear whether this action will provide a clinical benefit.
The FDA used the ‘Accelerated Approval pathway’ for this decision. This pathway enables earlier access to treatments which could benefit people living with serious diseases like Alzheimer’s disease. The FDA uses the pathway where there are very few other treatments available and where a new treatment is expected to have a beneficial effect.
The FDA has also requested a further clinical trial after this approval to ensure Aducanumab really is beneficial for people living with Alzheimer's disease. The approval means Aducanumab is available to people with Alzheimer’s disease in the United States.
The EMA announced their decision on Aducanumab and recommended the refusal of the application to license the drug for use as a treatment for Alzheimer’s disease in Europe. They concluded that there was currently insufficient evidence that Aducanumab was safe, effective and had clinical benefit for people living with Alzheimer’s disease.
The EMA noted some concerns around the safety of the drug in their decision and took the opinion that the benefits of Aducanumab did not outweigh the risks.
The EMA’s recommendation will now be passed to the European Commission, who will formalise the decision.
What does this mean for people living with dementia in the UK?
In light of this decision, Aducanumab remains unavailable for people living with Alzheimer’s disease in Europe and in the UK.
The UK has a medicines regulation body called the Medicines and Healthcare products Regulatory Agency (MHRA). Although the EMA have made their decision for Europe, we await the decision by the MHRA, on whether or not Aducanumab will be approved as a treatment for Alzheimer’s disease in the UK.
However, in Government guidance published in January 2021 it is stated that the MHRA may rely on decisions taken by European Commission for the next two years. This suggests that Aducanumab may not be approved for use in the UK, however we will need to wait for the MHRA to announce their official decision.
It’s disappointing that there are still no treatments that can slow down the progression of Alzheimer’s disease available in the UK. However, it is crucial that any new treatment is safe and provides clinical benefit for people living with Alzheimer’s disease before it is made available. It is essential that regulatory authorities are confident that Aducanumab is both effective and safe before it can be made available as a treatment.
Aducanumab is likely to continue to split opinion. However, the results of additional clinical trials will help to bring clarity to the effectiveness and benefits of Aducanumab.
Biogen has 60 days to appeal the decision made by the EMA.
We await the decision by the MHRA on whether or not Aducanumab will be approved as a treatment for Alzheimer’s disease in the UK. If approved by the MHRA, Aducanumab will also need to be reviewed by the National Institute of Health and Care Excellence (NICE) before it can be made available through the NHS in the UK.
Aducanumab may be the first drug which aims to slow the progression of Alzheimer’s disease to reach this stage, but it will not be the last. Even when clinical trials are unsuccessful, researchers learn more and more about Alzheimer’s disease and how we might be able to treat it in the future.
This article was first published on 8 June 2021 and last updated on 22 December 2021.