Alzheimer’s disease remains one of the most challenging neurodegenerative disorders to treat, with its progressive cognitive decline and memory loss affecting millions worldwide. Recently, a new monoclonal antibody targeting amyloid plaques in the brain, donanemab, has been developed and successfully tested.
What is donanemab?
Donanemab (Kisunla™) is a monoclonal antibody developed by Eli Lilly specifically for early-stage Alzheimer’s disease. It’s mechanism of action consists in the targeting and clearing of beta amyloid plaques, one of the key pathological hallmarks of this disease. The U.S. Food and Drug Administration (FDA) recently approved this therapy for adults with mild cognitive impairment or mild dementia due to Alzheimer’s.
How Does donanemab Work?
Amyloid beta plaques accumulate in the brain during the early stages of AD, disrupting neuronal communication and triggering inflammation. Donanemab binds to a specific form of beta amyloid, which can be found only in plaques formed in the brain, facilitating its clearance through the immune system. This slows the progression of cognitive decline, allowing patients to maintain their independence and quality of life for longer.
Clinical Trial Success
The approval of donanemab is based on data from a large Phase III clinical trial called TRAILBLAZER-ALZ 2. In this trial, participants receiving donanemab experienced a significant reduction in amyloid plaque burden compared to those on placebo. Additionally, the treatment group showed slower cognitive and functional decline, particularly in patients with lower levels of tau protein, a marker associated with Alzheimer’s progression.
Side effects
The most common side effects include infusion-related reactions and amyloid-related imaging abnormalities (ARIA), such as swelling or bleeding in the brain. Despite these severe side effects in a significant percentage of the patients, the FDA considered its potential as an Alzheimer’s disease treatment to outweigh these side effects.

Future Directions
Long-term studies are underway to better understand donanemab safety profile and efficacy over extended periods. Additionally, combining donanemab with other emerging treatments, such as tau-targeting drugs or anti-inflammatory agents, could offer a promising approach for the early management of Alzheimer’s disease. The approval of this new therapy further highlights the importance of early diagnosis for efficient treatment.
For more detailed information, refer to the original study here.
Key milestones in the development and approval of donanemab.
By Omar Ben Mariem, Department of Pharmacological and Biomolecular Sciences, University of Milan
Source: doi.org/10.1007/s40265-024-02087-4