In the normal run of events, the approval of the first new drug for an illness in 18 years would be a cause for celebration. Especially when the drug is for the treatment of Alzheimer’s disease, which affects about 35 million people worldwide. But the recent decision by the US Food and Drug Administration (FDA) to approve the drug aducanumab – the first such drug to attempt to treat a possible cause of Alzheimer’s – has alarmed many experts.
Developed by biotechnology company Biogen, aducanumab attempts to treat a possible cause of the neurodegenerative disease, rather than just the symptoms.
Basing an Alzheimer’s drug approval on trial data that does not conclusively demonstrate that it could slow cognitive decline is seen as a dangerous precedent by many.
Aducanumab is not without significant side effects. About 40 per cent of treated participants in trials of the drug developed brain swelling
The brain is made up of billions of nerve cells that connect to each other. In Alzheimer’s disease, connections between these cells are lost. This is because proteins build up and form abnormal structures called “plaques” and “tangles”. Eventually nerve cells die and brain tissue is lost.
Current Alzheimer’s drugs address only disease symptoms, for example by delaying memory loss by a few months. Aducanumab, a monoclonal antibody given intravenously, clears out clumps of a protein in the brain called amyloid-β, which some researchers think is the root cause of Alzheimer’s. This is known as the amyloid hypothesis, but not every expert agrees that this protein is the definitive cause of the disease.
And so the FDA decision to approve the drug on the basis of its ability to reduce the levels of these plaques in the brain, rather than a demonstrable benefit in symptoms, is puzzling.
Aducanumab is not without significant side effects. About 40 per cent of treated participants in trials of the drug developed brain swelling. Most people didn’t have any symptoms related to the swelling, but they will need regular brain scans to avert potentially dangerous complications.
And it’s not as if the road to approval was a smooth one. In March 2019, two major trials into aducanumab were stopped by the company after an interim analysis suggested there was no benefit for patients with early onset Alzheimer’s disease.
But months later, Biogen brought the antibody back to the FDA, after looking at the data more closely. The slowing of cognitive decline was statistically significant in the subset of participants who received the highest dose of aducanumab, the re-analysis showed.
However, last November, 10 out of 11 independent members of a panel put together by the FDA to assess the trial data voted that it could not be considered as evidence of aducanumab’s effectiveness. And in a further twist, late last week the US regulator withdrew its blanket approval of the drug: now only patients with early-stage Alzheimer’s disease can take it, in line with the revised data supplied by Biogen showing a marginal benefit for this group.
Where does this leave patients in Europe? The European Medicines Agency (EMA) is currently considering an application, filed in 2020, to approve the use of aducanumab. A decision is expected by the end of this year. One hopes the EMA will call for further trials to provide additional evidence of the benefits of this drug for people with early Alzheimer's disease.
It is essential that European regulatory authorities are confident that this drug is effective and safe before it gets a green light. Based on current data, the only possible approval would seem to be for people with early-stage Alzheimer’s. But without additional trial data, such a decision would seem speculative, at best.
It is difficult to see how the FDA gave aducanumab its blessing. Yes, Alzheimer’s is a common condition without an effective treatment. But relying on this kind of data to see if the drug can improve cognition is risky, in my view.
Let’s hope the EMA adopts a more cautious approach in its appraisal of aducanumab.