What is donanemab? A Guide to the New Alzheimer's Drug

October 7, 2025 •

3 min read

In July 2024, the FDA granted traditional approval for donanemab (marketed as Kisunla™), a monoclonal antibody that targets and helps clear amyloid plaques in patients with early symptomatic Alzheimer's disease. This represents a significant advancement in treating the underlying pathology of the disease rather than just managing symptoms.

Quick Summary

Donanemab is an FDA-approved monoclonal antibody treatment for early-stage Alzheimer's disease, targeting and clearing amyloid plaques from the brain to slow cognitive decline.

Key Points

What is donanemab?: It is an FDA-approved monoclonal antibody (Kisunla™) that targets and clears beta-amyloid plaques in the brains of patients with early Alzheimer's disease.
Mechanism of Action: Donanemab binds to a specific pyroglutamate-modified form of amyloid, triggering microglial cells to clear the plaques from the brain.
Clinical Efficacy: In the TRAILBLAZER-ALZ 2 trial, donanemab slowed cognitive and functional decline by up to 35% in patients with low-medium tau pathology.
Discontinuation of Treatment: Unlike other similar therapies, donanemab treatment can be stopped once brain amyloid plaque levels are significantly cleared, based on monitoring with PET scans.
Significant Risks: The main safety concern is Amyloid-Related Imaging Abnormalities (ARIA), which includes brain swelling (ARIA-E) and bleeding (ARIA-H), and requires regular MRI monitoring.
Patient Eligibility: Donanemab is indicated for patients with mild cognitive impairment or mild dementia due to Alzheimer's who have confirmed amyloid plaques and are carefully screened for risk factors.
Comparison to Lecanemab: Donanemab is a monthly infusion that targets mature plaques, while lecanemab is a biweekly infusion targeting earlier amyloid forms.

Understanding Donanemab: Mechanism of Action

Donanemab (Kisunla™) is a humanized monoclonal antibody developed by Eli Lilly that is designed to target and clear amyloid-beta (Aβ) plaques from the brain. It targets a modified form of amyloid known as N3pE-Aβ, present in mature plaques. When donanemab binds to these plaques, it's thought to activate microglia, the brain's immune cells, to clear the Aβ-antibody complexes, reducing the overall amyloid plaque load.

How Donanemab Targets Amyloid Plaques

Monoclonal antibodies are lab-produced antibodies engineered to target specific biological markers, such as the N3pE-Aβ form of beta-amyloid. By binding to this form, donanemab initiates a response leading to the degradation of the plaque structure by microglia, sometimes called "bystander clearance".

Clinical Efficacy and Patient Outcomes

The efficacy of donanemab was shown in the Phase 3 TRAILBLAZER-ALZ 2 trial with over 1,700 participants with early symptomatic Alzheimer's. The study found that donanemab significantly slowed cognitive and functional decline. For the low-medium tau population, decline was slowed by 35% compared to placebo at 18 months. The combined tau population saw a 22% slowing of decline.

Key findings from the TRAILBLAZER-ALZ 2 trial included significant plaque reduction, stabilized cognition at one year, delayed progression to the next stage, and the potential to stop treatment once brain plaque levels are below a threshold.

The Administration Process

Donanemab is administered via intravenous (IV) infusion every four weeks.

Dosing Schedule: Donanemab is administered according to a specific schedule outlined by healthcare providers.
Infusion Duration: Each infusion takes about 30 minutes, with potential monitoring afterward.
Monitoring: Regular MRI scans are necessary to check for amyloid-related imaging abnormalities (ARIA).

Potential Risks and Side Effects

Amyloid-Related Imaging Abnormalities (ARIA)

ARIA is a common side effect of anti-amyloid therapies detected by MRI. It includes:

ARIA-E (edema/effusion): Swelling in the brain.
ARIA-H (hemorrhage): Microscopic or larger bleeding.

ARIA can be asymptomatic or cause symptoms like headache, confusion, or dizziness. Severe cases are rare but possible. Risk is linked to the APOE ε4 genotype. The FDA has issued a boxed warning about ARIA risk.

Infusion-Related Reactions

Infusion reactions can occur, with symptoms including fever, chills, nausea, headache, or rash. These can often be managed with pre-medication.

Donanemab vs. Lecanemab: A Comparison


Feature	Donanemab (Kisunla™)	Lecanemab (Leqembi™)
Mechanism	Targets a modified form of Aβ in mature plaques.	Targets soluble amyloid-beta protofibrils.
Dosing Frequency	Monthly IV infusion.	Biweekly IV infusion.
Treatment Duration	Can be stopped once amyloid plaque levels are reduced.	Requires ongoing treatment.
Clinical Trial Efficacy (Slowed Decline)	Up to 35% in low-medium tau patients.	Approximately 27% in early-stage patients.
ARIA Rates (Phase 3 Trials)	ARIA-E: ~24%; ARIA-H: ~31%.	ARIA-E: ~13%; ARIA-H: ~17%.
Symptomatic ARIA Risk	~22% of ARIA events were symptomatic.	~2.8% of patients experienced symptomatic ARIA.

Who is an Eligible Candidate for Donanemab?

Donanemab is for patients with early symptomatic Alzheimer's with confirmed amyloid plaques. This includes individuals with mild cognitive impairment or mild Alzheimer's dementia. Confirmation of plaques via PET scan or CSF testing and a screening MRI are required before treatment. It is not for moderate-to-severe dementia.

Conclusion: The Future of Alzheimer's Treatment

Donanemab offers a significant advancement in Alzheimer's treatment by targeting amyloid pathology and potentially allowing treatment to stop once plaques are cleared. However, ARIA is a key risk, requiring careful screening, APOE4 testing, and monitoring. Continued research may lead to earlier use and combination therapies, offering hope for delaying progression. For more information, consult official resources like the FDA website {Link: FDA website https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-treatment-adults-alzheimers-disease}.

Frequently Asked Questions

Donanemab is administered as an intravenous (IV) infusion every four weeks. The dosing schedule is determined by a healthcare provider.

ARIA, or Amyloid-Related Imaging Abnormalities, refers to swelling (ARIA-E) and/or bleeding (ARIA-H) in the brain detected by MRI. It is a known side effect of anti-amyloid therapies like donanemab and is more common in individuals with the APOE ε4 gene.

The FDA approved donanemab for people with early symptomatic Alzheimer's, including those with mild cognitive impairment (MCI) or mild dementia, and confirmed amyloid pathology.

No, donanemab is not a cure for Alzheimer's disease. It is a disease-modifying therapy designed to slow the progression of cognitive and functional decline by targeting the underlying amyloid pathology.

While both are anti-amyloid monoclonal antibodies, donanemab targets mature plaques monthly, whereas lecanemab targets earlier amyloid protofibrils biweekly. A key difference is that donanemab treatment may be stopped after plaques are cleared, while lecanemab is ongoing.

Patients receiving donanemab require regular MRI scans, especially during the initial months of treatment, to monitor for ARIA. Genetic testing for the APOE ε4 allele is also recommended to assess ARIA risk.

One of the unique aspects of donanemab is that treatment can be discontinued once amyloid plaques are reduced to minimal levels, as confirmed by an amyloid-PET scan. Patients in clinical trials who reached this point and stopped infusions showed continued slower decline compared to placebo.