FDA to announce its decision on new Alzheimer’s drug

By Sarah Boseley

A new drug for Alzheimer’s disease, the first in nearly 20 years, may be approved in the US on Monday, which would trigger pressure to make it available worldwide.

Any decision is likely to be controversial. 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.

In November, the US Food and Drug Administration (FDA) rejected the application, but it is 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 are concerned that if the drug is approved largely because of the dearth of drugs for Alzheimer’s, it will lower the bar for the future. Alzheimer’s Research UK points out that there are 126 agents in 150 clinical trials at the moment.

Hilary Evans, the chief executive of Alzheimer’s Research UK, said: “Today’s decision from the FDA could be historic for people with early Alzheimer’s disease and their families in the US, and the outcome will be pivotal for dementia research. If aducanumab is approved in the US, it will be the first new drug licensed for nearly 20 years and the first ever to act on the underlying disease itself. Approval would bring renewed hope to many around the world, but UK regulators will still need to complete their own rigorous assessment of the data to decide whether aducanumab should be licensed in the UK.”

One of the FDA advisers, Dr Caleb Alexander, a drug safety and effectiveness expert at the Johns Hopkins Bloomberg school of public health, is unhappy that the data put forward to the regulator is 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 that if it is approved and comes into use, people would 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 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.

If aducanumab is approved by the FDA, licensing in the UK and Europe, where Biogen has also filed applications, could follow. But the bigger 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. It’s important we see a robust and evidence-based decision from regulators on whether any new medicine is safe and effective.

“If the FDA rejects the licence for aducanumab, it would be bitterly disappointing news for many, but not the end of the road in the search for life-changing new treatments for Alzheimer’s. With over 150 clinical trials currently testing a variety of different treatments for the disease, there is still reason to be hopeful.”