A controversial new drug for Alzheimer’s disease, the first in nearly 20 years, was approved in the US on Monday, which will trigger pressure to make it available worldwide in spite of mixed evidence over its efficacy.
While doctors, patients and the organisations that support them are desperate for treatments that can slow mental deterioration, the usefulness of the new drug, aducanumab, is disputed by scientists. Two trials were stopped in March 2019 because the drugs appeared not to work. The manufacturer, Biogen, said the drugs were unlikely to improve people’s memory and thinking.
But the company later announced that a reanalysis of more patient data from one of the trials involving people who had taken the drugs for longer showed that a high dose could slow the decline of memory and thinking skills and the ability to carry out activities in daily life. It applied to regulators for a licence.
The US Food and Drug Administration (FDA) has now approved the drug, but only on condition that those given it are part of what is called a phase 4 trial. This means they will be monitored by researchers to see how well they do on the drug and whether it really does slow the progression of mental decline.
“This does not mean there will be wide access,” said Prof Craig Ritchie, director of Brain Health Scotland, who thought the UK and European regulators would probably take a similar view of the drug.
“Use within the NHS, though, remains some months away and it is critically important that the safe use of this intervention in those people most likely to benefit is fully considered. We also need to ensure that we collect real world data on the benefits and side effects of the medication to help us to refine how to use this intervention well. It’s certainly a new chapter but by no means the end of the story.”
Some other scientists were amazed that the drug had been approved at all.
“As a dementia clinician and researcher with personal family experience of Alzheimer’s disease, I want to see effective dementia treatments as much as anyone,” said Robert Howard, Professor of Old Age Psychiatry at UCL.
“I consider the approval of aducanumab 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.
“Amazingly, the FDA have sidestepped available clinical trial outcomes data that indicate the drug probably doesn’t work.”
The FDA rejected the application in November, when its members were split on the merits. Three of its advisers went public, writing in a scientific journal that there was not enough evidence that it worked. They were concerned that if the drug were approved largely because of the dearth of drugs for Alzheimer’s, it would lower the bar for the future.
One of the FDA advisers, Dr Caleb Alexander, a drug safety and effectiveness expert at the Johns Hopkins Bloomberg school of public health, was unhappy that the data put forward to the regulator was a reanalysis after the trial was terminated. He told the New York Times it was “like the Texas sharpshooter fallacy – the idea that the sharpshooter shoots up a barn and then goes and draws a bullseye around the cluster of holes that he likes”.
The drug is a monoclonal antibody that targets the buildup of amyloid protein plaques in the brain, which are believed to be a cause of Alzheimer’s disease. Most of the drugs designed for Alzheimer’s have attempted to clear these plaques.
Aducanumab does appear to do this in some patients, but only at an early stage in the disease. That means people have to be tested to establish that they have the disease. Many people with memory loss are reluctant to come forward for testing because, at the moment, there is little treatment.
The few Alzheimer’s medicines there are seem to have limited effects. There was a huge battle to obtain the drug Aricept, also known as donepezil, when it was approved more than 20 years ago. At that time, it was hailed as a breakthrough – but largely because of the absence of anything else. It has become clear that it slows mental decline for some months, but that over the long term it makes little difference.
The drug would have significant consequences for the NHS if it became widely prescribed. Patients with very early memory problems will need PET scans of the brain to establish whether they have amyloid plaques. That requires not only equipment but also trained staff. There would probably be debate over whether the cost to the NHS is worth what may turn out – as it has with other drugs – to be a small and short-lived improvement in symptoms.
