Aducanumab: Where do we go from here?
By Hilary Evans | Friday 17 December 2021
Today a key committee for the EU drug regulator, the European Medicines Agency (EMA), has announced that it has recommended refusing a licence for the Alzheimer’s drug aducanumab.
We know today’s announcement will come as bitterly disappointing news for people with Alzheimer’s and their families, many of whom have been waiting for the outcome of this announcement for some time.
The drug was reviewed by the EMA’s Committee for Medicinal Products for Human Use (CHMP). They concluded that although aducanumab could reduce a key Alzheimer’s protein called amyloid in the brain, the data they reviewed didn’t show a clear link between this effect and benefits to patients’ lives.
The committee’s view was that results from the main clinical studies were conflicting and did not show overall that the drug was effective at treating people with early Alzheimer’s disease.
In addition, the committee raised concerns that the studies did not show that the medicine was sufficiently safe. Evidence from the clinical trials show that the drug can cause swelling and bleeding in the brain, which could potentially cause harm.
What is aducanumab?
Current treatments for Alzheimer’s work to reduce the symptoms for a time. But if approved, aducanumab would have been the first new Alzheimer’s drug in the EU for nearly 20 years, and the very first with the potential to tackle the underlying disease.
Aducanumab is an antibody designed to target amyloid, a protein that builds up in the brain at an early stage of Alzheimer’s disease. It is given by an infusion (IV drip into the bloodstream), and was trialled in people with mild cognitive impairment (MCI) and early Alzheimer’s.
But the decision to file for regulatory approval took the dementia research community by surprise.
Biogen, the company behind aducanumab, had stopped its phase III trials early in 2019, after an interim analysis suggested the drug would not be effective. But later that year, the company revealed that a new analysis with more long-term trial data had shown that it could successfully clear amyloid from the brain. That data showed that in one of the two trials, people on higher doses of the drug also had a slower decline in their memory and thinking.
Over recent months, the trial results and regulatory submissions have sparked debate about how to judge the effectiveness of new Alzheimer’s treatments, and how meaningful the impact of a drug would need to be on someone’s day-to-day life to meet that threshold.
What people with Alzheimer’s need is a medicine that improves their lives. The EMA committee’s decision reflects a lack of sufficient evidence that any potential benefits of aducanumab would outweigh its risks.
Why did two regulators come to different conclusions?
The EMA’s recommendation follows a decision by the US Food and Drugs Administration (FDA) in June to approve the drug for use in the US. People watching these decisions may be wondering why two different regulators could make such different rulings.
The FDA approved aducanumab via its Accelerated Approval Pathway. This means a licence can be granted based on a drug’s effect on a biological marker of disease, rather than its proven ability to improve people’s day-to-day lives.
This meant the FDA was able to consider aducanumab’s effect on amyloid levels in the brain, rather than how it affected people’s memory and thinking. The FDA now requires a post-approval trial to verify that the drug provides the benefits that patients and doctors would expect.
The EMA does not have a similar pathway to approval. Under its pathway, its committee considered whether the trial results showed evidence that the drug was safe for use, and whether it was able to effectively slow the decline in people’s memory and thinking.
In response to today’s decision, Biogen has announced they will ask the EMA committee to re-examine their decision. If this is unsuccessful, the company may decide to submit a separate application to the UK regulator, the Medicines and Healthcare Products Regulatory Agency (MHRA), to seek a licence for aducanumab here in the UK.
What does this mean for research now?
Around two thirds of the almost one million people living in the UK with dementia have Alzheimer’s disease and current treatment options are limited.
Alzheimer’s Research UK remains committed to finding safe, effective treatments that will significantly improve people’s lives. Thanks to your unwavering support, our scientists continue to make progress and each new research discovery brings us closer to making those breakthroughs possible.
With over 125 drugs for Alzheimer’s currently in clinical trials, it’s a question of when, not if, new treatments will come. But today’s decision needs to be a catalyst for increased and sustained investment into this area.
It’s vital that regulators agree that any new treatment is safe and effective before granting a licence. What people with Alzheimer’s need is a medicine that improves their lives. But when dealing with first-in-kind drugs for any disease, it’s not unusual for the benefits to be small, or the side effects to be big, and regulators need a clear way of assessing whether a new drug brings real improvements to people’s day-to-day lives.
All of this means government, regulators, and life sciences companies must work together to speed up access to future Alzheimer’s treatments. We will continue our work with key decision-makers so that when an effective drug does become available, it can be rolled out as quickly and safely as possible so that people with dementia can benefit without delay.
With a disease as complicated as Alzheimer’s the answers won’t be easy, but we don’t doubt for a second that we will find them. With you by our side, our scientists are making incredible discoveries. And for as long as there are people and families affected by dementia, our scientific research goes on.
Research needs all of us, thank you for your continued support.
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