The FDA has approved the dementia drug Aducanumab for clinical use for people living with Alzheimer's disease in the USA. Find out more about the drug, its path to approval, and what it means for people with dementia in the UK.
Over 850,000 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 126 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.
Over the last 18 months, the Food and Drugs Administration (FDA) - the drug regulatory body in the USA - has reviewed the evidence on how effective Aducanumab is at slowing the progression of Alzheimer’s disease. The FDA has now approved the drug for clinical use in people with Alzheimer’s disease.
‘This is the first ever Alzheimer's disease modifying drug to be approved, representing a promising step in the quest to find dementia treatments’
However, it is currently only available for use in the USA.
Biogen – the pharmaceutical company who owns Aducanumab – have also submitted an application to the European Medicines Agency (EMA), the EU equivalent of the FDA. UK regulatory bodies will also rigorously review the clinical trial data showing the effects of Aducanumab. These bodies will then make a decision as to whether to approve the drug for use in Europe and in 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 have been the results of clinical trials using this drug?
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 reported 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. It will be important to see the clinical findings of the full trials once completed in 2022. This will give us a better idea of Aducanumab’s effectiveness.
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 have now reached their final decision, approving 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 concluded that the benefits of Aducanumab for patients with Alzheimer’s disease outweigh the risk of the treatment.’
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 will be able to be accessed by people with Alzheimer’s disease in the United States.
What does this mean for people living with dementia in the UK?
Whilst exciting that research has brought us to this point, Aducanumab is not yet available to people with Alzheimer’s disease in Europe or the UK.
Biogen have also applied to the EMA for Aducanumab approval, which we await the outcome of. Any new medication will also need to be reviewed by UK regulatory bodies and by the National Institute of Health and Care Excellence (NICE) before it might be made available through the NHS in the UK.
‘It is unlikely we will know if Aducanumab will be approved and ready for use in the UK until at least 2022.’
Taking a step back
It is possible the EMA could call for further trials to provide additional evidence of the benefits of this drug for people with early Alzheimer’s disease. It is essential that regulatory authorities are confident that this drug is effective and safe before it may be made available to people with Alzheimer’s disease.
It is also important to remember that, if approved, Aducanumab has only been tested in people with early-stage Alzheimer’s disease.
Although the FDA is making the drug available to all people living with Alzheimer’s disease, it is unclear how beneficial this treatment will be in more advanced stages. Also, in the UK, the drug may only be approved for those living with the early-stages of the condition based on the current data.
‘The decision by the FDA to approve Aducanumab has not been without controversy, splitting the dementia research community.’
Some believe it will bring greater focus and investment to the field of dementia research. Others believe there is not enough evidence to demonstrate a true benefit for people with Alzheimer’s disease.
The next steps for the drug in Europe and UK are 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.
This article was first published on 8 June 2021 and last updated on 14 June 2021.