What are lecanemab and donanemab?

Lecanemab and donanemab are medications that help remove a protein called amyloid from the brain. This protein builds up in people with Alzheimer’s disease.

When and how were these drugs approved?

• Lecanemab (Leqembi™) was approved by the FDA on July 6, 2023.
• Donanemab (Kisunla™) was approved on July 2, 2024.

Both drugs were tested in clinical trials. In these trials, patients treated with lecanemab or donanemab had less amyloid in their brains compared to those who received a placebo (a treatment given in place of an active treatment). Both groups still experienced decline in thinking and independence, but the decline was less severe for those who received treatment.

Some doctors think the benefits of these drugs may not be significant for everyone, while others believe they can help certain patients.

Who should get these treatments?

These drugs are approved for patients with mild Alzheimer’s disease, specifically those with mild cognitive impairment (MCI) or mild dementia. Patients with moderate or severe dementia or other types of dementia are not eligible. Before starting treatment, your doctor will need to confirm the presence of amyloid in your brain using a PET scan or a spinal tap.

What are the risks?

The primary risk is brain swelling and bleeding from these medications. Brain swelling and bleeding related to anti-amyloid antibody therapy are called ARIA (Amyloid Related Imaging Abnormalities) and consist of either swelling (ARIA-E) or bleeding (ARIA-H). Patients on blood thinners, or with a specific genetic variation (one or two copies of APOE4) are at higher risk for these side effects. ARIA is also more likely to occur within the first 14 weeks of treatment.

Most patients who develop ARIA will show no symptoms associated with it. Those who do develop symptoms related to ARIA may experience (not an exhaustive list):

• Headache
• Confusion
• Dizziness
• Vision changes
• Nausea
• Difficulty walking
• Seizures

In rare cases, ARIA can be life-threatening. Safety monitoring for ARIA will require frequent MRI scans. For further details, please see here for the lecanemab package insert and here for the donanemab package insert.

• Lecanemab: About 20% of patients may experience brain swelling or bleeding.
• Donanemab: The risk of brain swelling and bleeding can be higher, at over 35%, but with a modified titration schedule, it can be closer to the risk posed by lecanemab.

Infusion-related reactions can also occur in about 20% of people treated with lecanemab, and most occurred with the first treatment. They occurred in almost 10% of patients treated with donanemab and typically occurred during the infusion or within 30 minutes after the infusion. These symptoms can include:

• Fever and flu-like symptoms (chills, generalized aches, feeling shaky, joint pain)
• Nausea
• Vomiting
• Low blood pressure
• High blood pressure
• Low oxygen levels in the blood
• Difficulty breathing
• Headache
• Sweating
• Chest pain
• Irritation of skin

Approximately 40% of patients treated with lecanemab also had a temporary decrease in lymphocyte count, and 20% had an increase in neutrophil counts. Safety monitoring will include laboratory blood tests. (For further details, please see here for the package insert for lecanemab and here for donanemab).

How are these drugs given?

• Lecanemab: Administered through an intravenous (IV) infusion every 2 weeks for 18 months and then every 4 weeks thereafter
• Donanemab: Will be given through an IV infusion every 4 weeks until amyloid is cleared from the brain.

Are these treatments covered by insurance?

Medicare provides coverage for lecanemab and donanemab at this time, but patients will likely need to pay a portion of the cost. Coverage for other tests and scans that are needed for these therapies may vary. In general, coverage should be confirmed with your insurance.

Is this treatment right for me?

Lecanemab and donanemab may be recommended for patients who:

• Are aged 50-90 years
• Can have frequent MRI scans
• Have mild cognitive impairment or mild dementia due to Alzheimer’s disease
• Have confirmed amyloid in their brain
• Have a support person for frequent visits
• Undergo genetic testing for apolipoprotein E (ApoE) status

These treatments are not recommended for patients with:

• A history of stroke, TIA, or seizures
• Certain MRI abnormalities
• Allergies to monoclonal antibody treatments
• Bleeding disorders or those on blood thinners
• Other conditions like cancer

What is the difference between lecanemab and donanemab?

Both drugs target brain amyloid, but at different stages. Lecanemab targets amyloid before it forms plaques, while donanemab targets existing amyloid plaques. Lecanemab is given every 2 weeks, and donanemab is given every 4 weeks. There are no head-to-head randomized trials comparing lecanemab and donanemab, but they may be comparably effective. 

What should I do if I think I qualify?

If you are a Stanford Health Care patient and believe you qualify for treatment, please contact your care team to discuss further.