A participant in a clinical trial for aducanumab Kayana Szymczak/New York Times/Redux/eyevine
EXPECT to see debate over a new medicine to treat Alzheimer’s disease, called aducanumab, continue into 2022. Approved in the US last June, it is the first drug designed to treat a possible cause of this form of dementia, rather than the symptoms.
Aducanumab targets beta-amyloid, a protein that makes up plaques in the brain often seen in people with Alzheimer’s disease. But the drug has its critics as well as its cheerleaders. It hasn’t so far been proven to reduce memory loss and confusion, the chief symptoms of Alzheimer’s disease. Other commonly used medicines slightly alleviate these symptoms, but they don’t work for everyone and their effects wear off.
The US drug regulatory body, the Food and Drug Administration (FDA), approved aducanumab for use to combat early Alzheimer’s on the basis that it reduces the extent of amyloid plaques. These have long been seen as a “biomarker” of Alzheimer’s – in other words, a biological indicator of disease progression or severity.
Other medicines have been approved on the basis of biomarkers – for instance, levels of “bad cholesterol” are seen as a biomarker for heart disease. But for Alzheimer’s, it is still being debated if plaques are a valid biomarker.
There is growing concern that they may not be a cause but something more like a side effect of the disease process. Targeting the plaques is “reasonably likely to have a clinical effect”, says Susan Kohlhaas at Alzheimer’s Research UK. “But that’s still to be tested.”
When the FDA approved aducanumab, it went against the recommendations of its scientific advisory panel, which it usually follows – none of the 11 members considered it ready for approval and three members resigned in protest. The agency’s acting commissioner has since asked for an investigation to take place into the approval process.
The drug’s maker, Biogen, told New Scientist: “The approval of aducanumab by the FDA came after an extensive development, clinical testing and regulatory review process, supported by data of more than 3000 patients who participated in our trials.”
“We have to leave no stone unturned in our search for treatments”
One clinical trial showed that about 40 per cent of people on the drug experienced brain swelling or bleeding visible on a scan.
The FDA has said aducanumab should now be tested in a larger clinical trial, but in practice these can take many years to produce results. Few people may want to be in a placebo-controlled trial and risk taking dummy pills after the drug has been approved.
On 17 December, the European Medicines Agency decided not to approve aducanumab. It is also under review by the UK’s Medicines and Healthcare products Regulatory Agency.
If the drug is approved in the UK, it would need to be assessed to decide whether it is cost-effective for use by the national health services. In the US, it is priced at $56,000 a year.
“We have to make sure that we leave no stone unturned in our search for life-changing treatments,” says Kohlhaas. “It’s important to respect the regulatory process that happens in the UK and elsewhere. We also need to make sure that our treatments are evaluated for safety and effectiveness.”
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