A controversial new drug for Alzheimer’s disease, the first in nearly 20 years, was approved in the US on Monday, triggering 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, even though it 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 was approved largely because of the dearth of drugs for Alzheimer’s, it will 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.
Now that the drug has a licence, the battle will be over making it available. The UK’s memory clinics are already overburdened with dementia patients, as the population of elderly people increases.
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 may 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.
Evans said: “People with dementia and their families have been waiting far too long for life-changing new treatments but they need treatments that are safe and effective. Biogen’s decision to file for a licence for aducanumab came as a surprise to some doctors and researchers who had voiced concerns that the data is not yet strong enough to suggest aducanumab brings the benefits that people with Alzheimer’s and their families would rightly expect.”
If the FDA had rejected the licence for aducanumab, it would have been bitterly disappointing news for many, but not the end of the road in the search for life-changing new treatments for Alzheimer’s, she said. There are over 150 clinical trials currently testing a variety of different treatments for the disease.
