NIA statement on donanemab results: More Alzheimer’s research progress
Eli Lilly and Company recently shared results of its TRAILBLAZER-ALZ 2, phase 3, 18-month Alzheimer’s disease clinical trial. Published in JAMA, Eli Lilly researchers found that the drug donanemab slowed the rates of cognitive and functional decline in participants who have early symptoms of Alzheimer’s. Specifically, 47% of those who received the drug, compared to 29% who received a placebo, showed no signs of cognitive decline after one year of treatment. Donanemab is an antibody developed by Eli Lilly to reduce the harmful effects of beta-amyloid, a protein often found in the brains of people with Alzheimer’s.
This is another set of promising results to recently come out of an anti-amyloid therapy clinical trial. These follow last year’s published results from Eisai and Biogen showing that lecanemab-irmb (Leqembi), another anti-amyloid therapy, also slowed cognitive decline in people who have early forms of Alzheimer’s. Earlier this month, on July 6, the U.S. Food and Drug Administration granted traditional (full) approval for lecanemab-irmb for the treatment of Alzheimer’s disease.
The TRAILBLAZER-ALZ 2 trial recruited participants, 60 to 85 years of age, with early symptomatic Alzheimer’s, specifically either mild cognitive impairment or Alzheimer’s disease with mild dementia. The trial’s results met the primary endpoint and the secondary endpoints measuring cognition and function. The combined treatment group showed a slowing of clinical decline by 22.3% compared to the placebo group. The incidence of serious adverse events was 17.4% for those who received donanemab and 15.8% for those who received a placebo. Four treatment-related deaths occurred during the trial: three were people who received donanemab and one an individual who received the placebo. The three donanemab-related deaths were attributed to factors detected by neuroimaging known as amyloid-related imaging abnormality (ARIA). Some participants in other anti-amyloid trials have also experienced serious side effects.
Alzheimer’s disease and related dementias are complex disorders, caused by a constellation of overlapping and intertwined chains of biochemical reactions that wreck the brain. Successfully treating each individual’s dementia will likely require a diverse set of preventative and diagnostic therapies. The data reported in these donanemab and lecanemab studies suggest that anti-amyloid therapies may, at least, be the first of many other treatments.
NIA currently funds a diverse portfolio of more than 450 active clinical trials on Alzheimer’s disease and related dementias. In the coming years, we anticipate results from these trials will sharpen our view of how the anti-amyloid therapies, as well as novel therapeutic strategies, may be harnessed, either alone or in combination, to reduce the burden of these conditions.
For example, later this year we anticipate the publication of results from the Hope 4 MCI study phase 3 clinical trial. This study tested whether levetiracetam (AGB101), a drug traditionally used to treat some forms of epilepsy, can also slow cognitive and functional impairment in people who have mild cognitive impairment due to Alzheimer’s disease.
Another example is the Metformin in Alzheimer’s dementia Prevention (MAP) study. Researchers are testing whether the diabetes drug, metformin, may be effective at slowing cognitive decline in people who have early and late amnestic mild cognitive impairment, a precursor to Alzheimer’s. A phase 3 clinical trial is expected to be completed in April 2026.
NIA continues to enhance and expand our diverse dementia research portfolio. We extend sincere and grateful thanks to those who participate in dementia clinical trials as well as to all researchers who are searching for effective dementia treatment and prevention approaches.
Richard J. Hodes, M.D.
Director, National Institute on Aging
National Institutes of Health