Alzheimer’s drug donanemab helps most when taken at earliest disease stage, study finds

But the drug, an antibody that attacks the protein amyloid, does not work as well in people with more advanced disease.

• Sara Reardon

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A scan (artificially coloured) of the brain of a person with Alzheimer’s disease.Credit: K H Fung/Science Photo Library

An experimental drug can slow progression of Alzheimer’s disease in those who start taking it when the disease is still in its early stages. The drug, a monoclonal antibody called donanemab, does not improve symptoms. But among people who started taking it at the earliest stages of Alzheimer’s, 47% had no disease progression on some measures after one year, compared with 29% who took a placebo.

The drug does not provide as much benefit to people at later stages or those with a common genetic variation that raises the risk of the disease.

The results are “very encouraging”, says neurologist Reisa Sperling at Harvard Medical School in Boston, Massachusetts, particularly because they are similar to those of a similar drug called lecanemab. “It makes me feel we are on the right track.”

Donanemab’s manufacturer Eli Lilly, based in Indianapolis, Indiana, presented the results of the 1,736-person trial today at the Alzheimer’s Association International Conference (AAIC) in Amsterdam, and published them¹ in JAMA. The company released partial results in May, but researchers still had questions about the drug’s safety and efficacy in certain groups.

Sticky target

Like many others in the newest generation of Alzheimer’s drugs, donanemab is a monoclonal antibody that targets amyloid, a sticky, neuron-damaging protein, in the brains of people with dementia. Donanemab, like lecanemab and the related drug aducanumab, can cause a condition called amyloid-related imaging abnormalities (ARIA), which sometimes leads to potentially fatal brain bleeding and seizures. Around one-quarter of the participants in Eli Lilly’s phase III trial developed ARIA, and three died of the condition. ARIA was most common among study participants who carry the APOE4 genetic variation, which raises the risk of developing Alzheimer’s.