Alzheimer’s Drug Donanemab Might Slow Down Cognitive Decline


As per Nature, pharmaceutical company Eli Lilly announced on May 3 that its experimental drug donanemab had been shown to reduce the cognitive decline associated with Alzheimer’s disease. This is the second time an experimental drug has shown such a reduction, with competitor lecanemab having already shown similar results.  

Donanemab and lecanemab both target the amyloid protein that is thought to cause dementia by accumulating in the brain and damaging neurons. The trial results for donanemab provide strong evidence that amyloid is a crucial driver of Alzheimer’s, according to Jeffrey Cummings, a neuroscientist at the University of Nevada, Las Vegas. He adds that the results are “transformative in an enormously important way from a scientific point of view” and “terrific.”  

However, some researchers warn that until the full results are published, questions remain about the drug’s clinical usefulness and whether the modest benefit outweighs the risk of harmful side effects. Marsel Mesulam, a neurologist at Northwestern University in Chicago, is more cautious and says, “the results that are described are extremely significant and impressive, but clinically their significance is doubtful.” He adds that the modest effect suggests that factors other than amyloid contribute to Alzheimer’s disease progression and that there will be no magic bullet for the disease.  

Eli Lilly said in a press release that people with mild Alzheimer’s who received donanemab showed 35% less clinical decline over 18 months than those who received a placebo. They also showed a 40% decline in their ability to perform daily tasks. The company plans to present the full results at a conference in July and publish them in a peer-reviewed journal. It plans to apply for approval by the US Food and Drug Administration (FDA) in the next two months.  

FDA approval would make donanemab the third new Alzheimer’s treatment in two years. In January, the agency granted accelerated approval to lecanemab, made by Biogen in Cambridge, Massachusetts, and Eisai in Tokyo. A study published in November showed that lecanemab slowed cognitive decline in 1,800 patients by 27% over 18 months. Based on evidence that it could reduce amyloid plaques in the brain, the FDA had previously approved aducanumab, also made by Biogen and Eisai. However, whether this leads to a meaningful clinical benefit for people with the disease is still unclear. 

Donanemab’s trial differed from lecanemab’s in that people stopped taking the drug once their amyloid levels had dropped below a certain threshold. About half of the trial participants were able to stop taking the drug in less than one year. However, some experts worry that stopping the drug could cause the disease to rebound or worsen, as with many psychiatric drugs. They warn that longer-term follow-up studies will be needed.  

Eli Lilly also found that donanemab worked best in people whose brains contained only moderate levels of tau protein, which is also associated with Alzheimer’s progression. The company had calculated its results among its 1,182 trial participants who had moderate tau levels. However, it said that the improvement was still statistically significant when they combined these patients with the 552 who had high levels of tau.  

However, donanemab and lecanemab carry a high risk of side effects, particularly a set of conditions called amyloid-related imaging abnormalities (ARIA) that can lead to seizures and bleeding in the brain. Researchers think that by attacking amyloid plaques, the antibodies inadvertently weaken blood vessels in the brain, and the effects are especially pronounced among people taking anticoagulant drugs. Eli Lilly’s press release said that ARIA rates were several. 

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