In the donanemab trial, 47 percent of people on the drug did not get significantly worse over a year. On placebo, the figure was 29 percent. That gap is the headline result behind the second Alzheimer’s antibody to win approval, and it is a modest one.
Donanemab, sold as Kisunla and made by Eli Lilly, is a monoclonal antibody. So is lecanemab, sold as Leqembi, which got there first. Both bind to amyloid, the protein that builds up in the brain early in Alzheimer’s. Unlike older treatments, which only ease symptoms, they go after the underlying disease. The FDA approved lecanemab on July 6, 2023 and donanemab on July 2, 2024. Britain’s MHRA licensed donanemab on October 23, 2024.
What the trial showed
Lilly’s TRAILBLAZER-ALZ 2 trial enrolled more than 1,700 people with early Alzheimer’s and compared the drug with a dummy infusion. Among patients with low to medium levels of tau, a second Alzheimer’s protein, donanemab slowed decline in memory and thinking by about a third, 35 percent, over 18 months. Those patients also saw 40 percent less worsening in everyday tasks such as managing money, driving and keeping up hobbies. Across the group, donanemab cut the risk of moving to the next stage of the disease by 39 percent.
It did nothing measurable for people with high tau. Tau builds up later than amyloid, which suggests the drug works best at the earliest stage.
A small subgroup of about 200 people in the very earliest stage seemed to do far better, with a 60 percent slowing. Alzheimer’s Research UK warns that the group was too small to trust that number. Some newspapers led with it anyway in May 2023. Lilly is now testing the drug in a bigger group to check.
How the two drugs differ
Stanford Health Care, whose neurologists prescribe both, says lecanemab targets amyloid before it forms plaques while donanemab goes after plaques already formed. No head-to-head trial exists, though the two may work about equally well.
Dosing differs. Lecanemab is an infusion every two weeks for 18 months and every four weeks after that. Donanemab is given every four weeks, and patients can stop once amyloid is cleared. In the trial, almost half of those on donanemab were able to stop within a year. Alzheimer’s Research UK says that could make its long-term cost lower.
Risks and who qualifies
Both drugs can cause ARIA, swelling or bleeding in the brain that shows up on MRI scans. In the donanemab trial, swelling appeared on the scans of one in four participants, and one in 20 had symptoms. Less than two in 100 had serious swelling, and that included two deaths attributed to it, plus a third patient who died after a serious episode. Stanford puts the swelling and bleeding risk at about 20 percent for lecanemab and over 35 percent for donanemab, though a modified dosing schedule can bring the latter closer to lecanemab.
People on blood thinners or with one or two copies of the APOE4 gene face higher risk. Anyone with two copies is ruled out of donanemab on safety grounds. Treatment is limited to mild cognitive impairment or mild dementia, and a PET scan or spinal tap has to confirm amyloid first. Patients need frequent MRIs.
The trial had limits. Nine in 10 participants were white, and it lasted only 18 months, so long-term effects are unknown.
In the UK, NICE rejected donanemab for England and Wales in June 2025, and the Scottish Medicines Consortium reached the same conclusion. NICE judged the modest benefit did not justify the cost of overhauling diagnosis, and Alzheimer’s Research UK notes that only one in 50 people diagnosed with Alzheimer’s has had the detailed testing needed. In the US, Medicare covers both drugs, though patients will likely pay part of the cost. Stanford advises patients to ask their care team whether they qualify.
Sources
- New Alzheimer’s drug, donanemab – what is it and how does it work? – Alzheimer's Research UK
- Antiamyloid
