What are Lecanemab and Donanemab?

 Lecanemab and Donanemab are drugs that target removal of brain amyloid, one of the proteins that builds up in the brain in people with Alzheimer’s disease. 

When were Lecanemab and Donanemab approved and what were the results of the clinical trials?

The FDA granted traditional approval for Lecanemab (Leqembi^TM) on July 6, 2023, and they granted traditional approval to Donanemab (Kisunla^TM) on July 2, 2024. The Lecanemab approval was based on data from a phase 2 clinical trial followed by a larger phase 3 clinical trial. In the phase 3 trial, approximately 1,800 patients with Alzheimer’s disease were treated for 18 months with either Lecanemab or placebo. Similarly, the data for Donanemab approval emerged from a phase 2 clinical trial as well as a phase 3 trial. In the phase 3 Donanemab trial, nearly 1750 patients with Alzheimer’s disease were treated for 76 weeks (17.5 months) with Donanemab or placebo.

In both the Lecanemab and Donanemab clinical trials, the group of patients who received treatment showed a reduction in amyloid plaque on PET scans compared with the group of patients who received placebo. In both trials, the treatment groups and placebo groups continued to experience decline in both cognition and independence, but the decline was less pronounced for patients who received treatment.

Some neurologists believe the differences between the treatment groups and placebo groups are too small to be meaningful in these trials. Others believe there may be a benefit for select patients.

Who should get Lecanemab or Donanemab? 

These drugs are approved only for patients with mild disease with a diagnosis of mild cognitive impairment due to Alzheimer’s disease or mild dementia related to Alzheimer’s disease. Patients with moderate or severe dementia or other types of dementia are not eligible. Before starting Lecanemab or Donanemab, your doctor will need to confirm the presence of amyloid in your brain. Your doctor will order either an amyloid PET scan or spinal tap.

What are some potential risks of Lecanemab and Donanemab? 

TLecanemab is known to cause brain swelling or bleeding (hemorrhage) in about 20% of patients. This risk is just above 35% with Donanemab. These conditions may be diagnosed as either:

• Amyloid related imaging abnormality-edema (ARIA-E)
• Amyloid related imaging abnormality-hemorrhage (ARIA-H)

Patients on blood thinners may be at a higher risk for more serious side effects. Patients who have a specific genetic variation, APOE4 are also at higher risk for ARIA, so genetic testing prior to receiving treatment is required.  ARIA is also more likely to occur within the first 14 weeks of treatment. A majority of 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.

Infusion-related reactions can occur in about 20% of people treated with Lecanemab and most occurred with the first treatment. They occurred in almost 9% 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 Lecanemab and Donanemab administered?

Lecanemab requires an intravenous (IV) infusion every 2 weeks at Stanford Health Care. Donanemab, once available at Stanford, will require an intravenous infusion every 4 weeks. Patients will need to go to a Stanford infusion center for these infusions.

Are Lecanemab and Donanemab covered by insurance or Medicare?

A statement on Medicare coverage for Lecanemab can be found here. Patients will need pay 20% co-insurance for Lecanemab, which will be $5300 annually as of 2024 (subject to change). Medicare will also pay for Donanemab with a similar co-insurance ($6400 as of 2024, subject to change). This will require a patient to: 1) have Medicare coverage, 2) have the correct diagnosis of mild cognitive impairment due to Alzheimer’s disease or mild dementia due to Alzheimer’s disease, and 3) participate in a registry. Additionally, coverage may or may not be complete for required safety MRI scans, genetic tests, blood tests, and other testing. Coverage by other insurance providers will depend on the plan.  

Is Lecanemab or Donanemab right for me?

Given certain questions about safety and monitoring, Lecanemab or Donanemab may be recommended only for patients who meet certain criteria. (For further details, please see the package insert for Lecanemab  and here for Donanemab)

Our neurologists will consider treatment for Stanford Health Care patients who are:

• Age 50-90 years
• Able to undergo frequent MRI scans
• Diagnosed with mild cognitive impairment or mild dementia due to Alzheimer’s disease
• Have PET scans or cerebrospinal fluid (CSF) which confirms the presence of brain amyloid
• Have a care partner or support for frequent visits (recommended)
• Undergo ApoE4 genotype testing

These treatments are not recommended for patients with:

• A history of stroke, TIA, or seizure
• MRI abnormalities with evidence of tumor or hemorrhage
• Hypersensitivity to monoclonal antibody treatment
• Bleeding disorders or those on blood thinners
• Immune conditions or those taking antibodies, immunosuppressants, or receiving plasmapheresis
• Other serious conditions such as cancer

What is the difference between Lecanemab and Donanemab?

Although both drugs target amyloid protein, one of the two proteins that accumulate in the brain in Alzheimer’s disease (the other protein is called tau), they target amyloid protein at different stages. Lecanemab targets amyloid fibrils before plaque formation, and Donanemab targets amyloid plaques (clumped fibrils). Additionally, Lecanemab is given every 2 weeks, while Donanemab is given every 4 weeks. As detailed above, the rate of ARIA is higher in Donanemab. Donanemab is also more expensive than Lecanemab (subject to change). Lecanemab slowed the rate of clinical decline by 27% while Donanemab slowed the rate of decline by 22% in their respective clinical trials. However, each trial used different measures of decline, and the patients recruited for each trial were not the same.

What should I do if I am Stanford Health Care patient and believe I qualify?

If you are a Stanford Health Care patient and believe that you qualify, please contact your care team and we will place you on a list to discuss further with your care team.