A drug called donanemab has been shown to slow cognitive decline by 35 per cent in people with early Alzheimer’s disease. However, there has been a mixed reaction as to how big of an impact this slowed decline will have on a person with Alzheimer’s life and some are concerned over the risk of serious brain swelling and bleeds.
Donanemab is an antibody treatment that is being developed by US pharmaceutical company Lilly. It binds to clumps of protein called amyloid plaques that build up in the brains of people with Alzheimer’s disease. This binding activates an immune response to clear them out.
The drug was evaluated in a clinical trial involving almost 1200 people aged 60 to 85 with early Alzheimer’s disease – defined as mild cognitive impairment and dementia due to the condition – in the US, Canada, UK, Australia, Japan and Europe. The participants received intravenous injections of donanemab or a placebo every two weeks over 18 months.
At the beginning and end of the trial, the participants were assessed on their cognitive skills and ability to discuss current events, manage their finances and conduct other everyday tasks.
Those taking donanemab had 35 per cent slower decline in their overall scores than those in the placebo group, according to a results summary released by Lilly on 3 May.
“The results of this study are very encouraging,” says Bruce Brew at the University of New South Wales, Australia. “While the full results are yet to be published, the data that have been released show it significantly slows progression of Alzheimer’s.”
Matthew Schrag at Vanderbilt University, Tennessee, has said that while the 35 per cent decline is a statistically strong effect, it may not be clinically relevant. “It doesn’t give people their memory back,” he tweeted.
Donanemab has safety concerns, with brain swelling occurring in 24 per cent of those who received the drug. This side effect was not reported among those in the placebo group. Brain bleeds affected 31 per cent of those on donanemab, compared with 13 per cent in the placebo group. These resolved with appropriate management in most cases, but three participants died.
“There are risks of serious side effects that need to be fully scrutinised before donanemab can be marketed and used,” says Kohlhaas.
In November, another experimental amyloid-clearing antibody treatment called lecanemab, developed by Japanese company Eisai, was reported to slow cognitive decline by 27 per cent in people with early Alzheimer’s disease over 18 months. It, too, was associated with brain swelling and bleeding in some people, and is awaiting regulatory approval.
There is already one amyloid-clearing antibody treatment for Alzheimer’s disease on the market: aducanumab, which was approved by the US Food and Drug Administration (FDA) in 2021. However, it has only been shown to clear amyloid from the brain rather than improving Alzheimer’s symptoms.
Lilly has said it will apply for regulatory approval for donanemab from the FDA this financial quarter.