Hopes have been raised that thousands of people in Britain could soon have access to the first new drug for Alzheimer’s disease in nearly 20 years after US health officials gave it approval in what has been hailed as a “major milestone”.
Scientists remain divided over the full impact of aducanumab, with many experts calling for more trials to confirm its effectiveness — but approval of the drug is still seen as a crucial step forward in treating people with early Alzheimer’s.
Leading charities in the UK have called on the government to prioritise and accelerate research into aducanumab, which could be used by at least 100,000 people who suffer from a mild form of the disease if Britain’s regulator were to authorise the therapy.
Hilary Evans, chief executive at Alzheimer’s Research UK, said the US Food and Drug Administration’s approval “marks a pivotal moment in the search for life-changing new treatments”, but said “renewed focus and investment” into researching the condition is needed across the world.
According to the World Health Organisation, an estimated 30 million people globally suffer from Alzheimer’s. In the UK, some 500,000 people are thought to be living with the disease.
Aducanumab, given as an infusion every four weeks, targets the causes of Alzheimer’s rather than the symptoms. It appears to clear harmful clumps of a protein called amyloid that accumulates in the brain of sufferers and damages cells, triggering the memory and communication issues that define dementia.
The FDA said there was “substantial evidence that aducanumab reduces amyloid beta plaques in the brain” and that this “is reasonably likely to predict important benefits to patients”.
In the UK, an application for authorisation has already been made to the Medicines and Healthcare products Regulatory Agency (MHRA). According to reports, a decision is expected in the autumn. If aducanumab is given the green light, it will then be assessed by the National Institute of Health and Care Excellence in terms of its value for money as an NHS treatment.
Alzheimer’s Research UK meanwhile said it has written to health secretary Matt Hancock asking the government to fast track the MHRA’s review of drug in the UK. Alongside the British regulator, the European Medicines Agency is also assessing aducanumab.
However, there is uncertainty among the scientific community over the drug, with questions yet to be answered over whether its ability to clear amyloid translates to a reduction or reversal in cognitive decline among patients.
Late-stage international trials involving more than 3,000 participants was halted in March 2019 after analysis showed that aducanumab, developed by Biogen, appeared to perform no better than a placebo drug in slowing the deterioration of mental and functional decline in Alzheimer’s patients.
However, several months later, the company reversed course, announcing that a new analysis of one of the trials showed the drug was effective at higher doses and that the FDA had advised that it warranted review.
Dr Mark Dallas, an associate professor in cellular neuroscience at the University of Reading, said the clinical trials failed to present “a clear picture” that the drug will be of “tangible benefit” to people living with Alzheimer’s.
Many scientists are also in agreement that aducanumab will only help to treat carefully selected patients in the earlier stages of disease.
Alzheimer’s can accumulate for up to two decades before dementia is diagnosed. During this period, patients may have no or only mild symptoms.
“To give treatments like aducanumab or similar drugs in the UK, we will need to diagnose Alzheimer’s earlier when people have only mild symptoms,” said Dr Elizabeth Coulthard, a senior lecturer in dementia neurology at the University of Bristol.
Over the past decade, more than 100 potential Alzheimer’s treatments have failed to secure regulatory approval. The last drug to be authorised as medication for the disease was memantine in 2003.
Professor Bart De Strooper, director of the UK Dementia Research Institute, said aducanumab’s approval marked a “major milestone” in treating the disease.
“However, I fear the controversy and uncertainly surrounding the trials will limit the impact of this new treatment for the disease,” he said.
“There are still many barriers to overcome including cost, eligibility and clinicians’ enthusiasm to prescribe a medicine whose effects are far from certain.”
Aducanumab is expected to be an expensive treatment. In the US, a year’s worth of therapy could cost $50,000, according to Professor Paul Morgan, director of the Systems Immunity Research Institute at Cardiff University.
Others have condemned the FDA’s approval. It “represents a grave error that will have only negative impact on patients and their families and that could derail the ongoing search for meaningful dementia treatments for a decade,” said Robert Howard, professor of old age psychiatry at University College London.
He said the FDA had “sidestepped” data from the 2019 clinical trials, during which patients were treated over an 18-month period with the drug.
Other scientists are worried that the FDA, in authorising aducanumab without a clear picture of its clinical benefits, has lowered the bar for other regulators reviewing amyloid-targeting drugs.
Dr Richard Oakley, head of research at Alzheimer’s Society, said this was “just the beginning of the road to new treatments for Alzheimer’s disease” – regardless of the decision reached by the MHRA and other medicines watchdogs.
“As this drug will only benefit a proportion of people in the early stages of Alzheimer’s disease, there are hundreds of thousands more who may not be eligible,” he said, “so we must keep searching for drugs for all stages of Alzheimer’s disease and for other types of dementia.”