May 4, 2023 — The investigational drug donanemab significantly reduced the decline in Alzheimer’s patients’ ability to think clearly and perform daily tasks in a large study of adults with early signs of the disease, according to first results.
Donanemab, made by Eli Lily and targeting amyloid plaques, a hallmark of Alzheimer’s disease, met the study’s primary and secondary endpoints involving measures of cognitive and functional decline, showing “significant clinical benefits,” the study said. drug maker in a press release.
Based on the results, Lilly said it plans to apply to the FDA for approval of the drug by the end of June.
In the randomized, double-blind, placebo-controlled trial, almost half (47%) of patients taking donanemab had no clinical progression at 1 year, compared with 29% of patients taking placebo.
Donanemab also slowed clinical decline by 35%, compared to placebo, and resulted in 40% less decline in the ability to perform daily activities.
Patients taking donanemab had a 39% lower risk of developing the next stage of the disease, compared with placebo.
In addition to slowing cognitive and functional decline, donanemab produced significant reductions in brain amyloid plaque levels as early as 6 months after treatment initiation.
As a result of achieving a specific level of amyloid plaque clearance, 52% of people in the study completed their treatment cycle after 1 year and 72% completed treatment after 18 months, Eli Lilly said..
“These are the strongest Phase 3 data for the treatment of Alzheimer’s disease to date,” Maria C. Carrillo, PhD, Alzheimer’s Association chief scientific officer, said in a statement.
People studied in the trial were classified into groups based on their level of the brain protein tau, a predictive biomarker of Alzheimer’s disease progression. The primary analysis population of 1,182 patients consisted of individuals with intermediate tau levels and clinical symptoms of Alzheimer’s.
The study also enrolled 552 people with high tau levels at the start of the study, representing a later stage of the disease.
In an analysis combining 1,736 participants with high and intermediate tau, donanemab also showed “significantly positive” results across all clinical endpoints, Eli Lilly said.
However, there were some side effects, consistent with earlier phases of the research, such as swelling of the brain and mini-brain bleeds, known as amyloid-related imaging abnormalities, or ARIA. Three deaths were attributed to varying degrees of the condition.
In the general donanemab treatment group, brain swelling occurred in 24% of people, and 6% had symptomatic abnormalities.
Mini-cerebral hemorrhages occurred in approximately 31% in the donanemab group and approximately 14% in the placebo group. Most cases of the disorder were mild to moderate and resolved or stabilized with appropriate treatment.
‘Encouraging’ results, long-awaited full data
In a statement from the nonprofit UK Science Media Center, Paresh Malhotra, PhD, professor of clinical neurology at Imperial College London, said these new findings “provide further evidence that antibody treatments that reduce amyloid in the brain may delay the decline in thinking and the ability to carry out activities of daily living in people with early Alzheimer’s disease.”
“These are really encouraging results and show that targeting the fundamental mechanisms of Alzheimer’s can make a difference in people’s lives,” he said.
Also opining, Catherine Mummery, MD, PhD, from University College London Hospitals NHS Foundation Trust, said the results confirm that “we are now entering the era of Alzheimer’s disease treatment.”
“After many years of negative assays, we now have consistent results across various anti-amyloid antibodies showing that removal of amyloid changes the course of the disease,” he said..
Mummery also noted that the way the drug is delivered could reduce the burden and cost of treatment.
“This drug was only given until the amyloid was reduced to a low enough point and then it was stopped, which was 52% over 12 months and 72% over 18 months. This may provide a way to ‘induce remission’ in Alzheimer’s disease and then monitor without treatment,” she said.
Liz Coulthard, PhD, associate professor of dementia neurology at the University of Bristol, took a more cautious view of the results. “At first glance, these data seem positive, but we need to see the full data set,” she said.
“There are significant side effects, and we need to know more about how they have affected people. We also need to know the long-term effects of donanemab,” he said.
More data from the study trial will be presented at the Alzheimer’s Association International Conference in July..
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