Key Points:
- A third Alzheimer’s drug, donanemab, is on its way to approval by the FDA.
- In trials, it slowed cognitive decline by 35% compared with placebo patients.
- However, there are side effects and, like the other two drugs, donanemab is only effective at the earlier stages of Alzheimer’s.
Donanemab is on its way toward approval as an Alzheimer’s drug by the FDA. If that happens, it will be the third drug approved for the neurodegenerative disease.
Donanemab is a monoclonal antibody, like the two earlier Alzheimer’s drugs—aducanumab (Aduhelm) and lecanemab (Leqembi). These drugs attack plaques in the brain that are made of amyloid, which disrupt cell function and lead to the rapid spread of tau. Both amyloid and tau contribute to the development of Alzheimer’s disease.
The clinical trial showed donanemab slowed cognitive decline by 35% compared with placebo in patients with low-to-intermediate levels of tau in the brain. These results are similar to those reported with Leqembi, which received FDA approval earlier this month. In the donanemab trial, patients also experienced a 40% lower risk of progressing from mild cognitive impairment to mild dementia, or from mild-to-moderate dementia.
Additionally, donanemab was better at removing amyloid plaques compared to Aduhelm and Leqembi. It reduced tau concentrations in the blood, but not in a key area of the brain.
As with the other two medications, patients with more advanced disease showed little to no benefit compared with those who received the placebo. Indeed, all three drugs work best for those in the earliest stages of Alzheimer’s.
Like the two other new Alzheimer’s drugs, donanemab was associated with ARIA, amyloid-related imaging abnormalities that may include brain swelling and microbleeds. Serious ARIA occurred in 3.7% of patients, including three deaths. Risks were higher among patients with the APOE4 gene, which is related to an increased risk for Alzheimer’s.
In a new article, Gil Rabinovici, MD, director of the UCSF Alzheimer’s Disease Research Center, said the clinical trial results are encouraging but an in-depth analysis is still needed to understand how these findings affect patient outcomes. While ARIA has generally been managed safely in clinical trials, Rabinovici urged caution as these drugs enter into real-world practice. He suggested limiting access to patients with normal pre-treatment MRIs, repeating MRIs at regular intervals and stopping or suspending treatment when ARIA occurs.
Given the anticipated high cost of donanemab and high patient demand, Rabinovici said it might make sense to limit the treatment duration to the time needed to clear amyloid plaques from the brain, which is the approach pioneered in the trial. He said this could “greatly enhance the feasibility of treatment for patients, clinicians, insurers and health systems.”