Lecanemab

What is lecanemab?

Lecanemab is a monoclonal antibody (a protein that helps your immune system target specific proteins for removal), and it is designed to remove a protein called amyloid beta from the brain. Amyloid beta is an important protein involved in the progression of Alzheimer’s disease. Lecanemab is given intravenously (infused through a vein) every 2 weeks. Lecanemab does not cure Alzheimer’s disease, but it does modestly slow the rate of progression in the earliest stages of Alzheimer’s disease. In a large clinical study, lecanemab slowed the rate of disease progression by about 20–30% after 18 months of treatment in patients with early Alzheimer’s symptoms. This effect translated to a roughly 6-month delay in symptom progression after 18 months of consistent treatment.

Who should consider treatment with lecanemab?

Lecanemab should only be considered for use in people who have a biomarker-confirmed diagnosis of Alzheimer’s disease in its mildest symptomatic stages. This may include people with symptoms consistent with mild cognitive impairment or the very earliest stages of dementia. There is no evidence that lecanemab is beneficial for people who don’t have mild cognitive impairment or mild dementia. Before drugs like lecanemab can be considered for use, a doctor must detect evidence of brain accumulation of Alzheimer’s disease proteins with either a lumbar puncture (also known as a spinal tap) or a specialized brain scan called an amyloid beta positron emission tomography (PET) scan. Lecanemab is only helpful for the removal of amyloid proteins and should not be used in patients diagnosed with other conditions that cause cognitive impairment and dementia (e.g., Lewy body dementia, vascular dementia, frontotemporal dementia, Parkinson’s disease). People who carry a specific gene version called APOE-ε4 experience a higher risk of side effects from lecanemab. Testing for this gene is required for all patients considering treatment with lecanemab.

Before considering treatment for Alzheimer’s disease, a person must first seek care from a specialist with the expertise necessary to complete an appropriate diagnostic assessment. The UCSF Memory and Aging Center Clinic is one of many centers with expertise in diagnosing Alzheimer’s disease.

What are some potential risks of lecanemab?

In a large clinical trial, about 1–2 in 20 patients stopped lecanemab due to new symptoms that began after treatment was started. 

Infusion reactions: The most common side effect of lecanemab is an infusion reaction, experienced by a little under 1 in 3 patients, usually after the first dose. Infusion reactions involve immune responses to drugs given through the blood and may include changes in blood pressure, changes in breathing, skin changes, fevers, and chills. While infusion reactions can be dangerous, the majority of infusion reactions related to lecanemab have been easily treatable and not severe.

ARIA: About 2 in 10 people who receive lecanemab develop brain changes called amyloid-related imaging abnormalities (ARIA), which involves brain bleeding, brain swelling, or a combination of the two. Only 1 in 5 people who develop ARIA from lecanemab experience symptoms (most commonly headache, visual changes, and confusion). ARIA changes are detected on brain magnetic resonance imaging (MRI) scans. About 1 in 10 patients with ARIA may have severe changes on brain MRI scans, though severe symptoms and complications occur in less than 1 in 100 patients with ARIA. Additionally, the majority (7–8 in 10 cases) of ARIA due to lecanemab resolves within 3–4 months. People who carry a specific gene version called APOE-ε4 are more susceptible to developing ARIA as well as serious complications from ARIA (especially if they carry two copies of the APOE-ε4 gene version). All patients must receive APOE gene testing before consideration of lecanemab use, so they can understand their unique risk of ARIA before moving forward with treatment. 

Contraindicated medication: Because of the risk of bleeding associated with lecanemab, we currently do not recommend that people on strong blood thinners (“anti-coagulants”) receive this treatment. To date, there have been a handful of deaths that have occurred from brain bleeding in patients treated with lecanemab, including at people who died after receiving a “clot-busting” medication to treat a stroke.

The potential risks and benefits of lecanemab must be thoroughly considered in each person individually. Some patients with Alzheimer’s disease may not be appropriate for treatment with lecanemab, due to their doctor’s concerns about their individual balance of possible risks and benefits from treatment. Additionally, before and after lecanemab is started, patients must receive special monitoring (including brain magnetic resonance imaging [MRI] scans) to screen for ARIA. Lecamemab treatment may be halted based on MRI findings.

How does lecanemab differ from aducanumab and donanemab?

Aducanumab (marketed as Aduhelm™) is a drug with a similar mechanism to lecanemab, but it targets a different version of amyloid beta. Two large trials of aducanumab in early symptomatic Alzheimer’s disease were discontinued prematurely, and one trial did not show a benefit in symptoms. The scope of clinical use of aducanumab is extremely limited, given its incomplete evidence of clinical benefit and lack of coverage by most insurers.

Donanemab is another drug in the same class as lecanemab and aducanumab, with a similar mechanism of action but different clinical profile, requiring only once-a-month dosing. So far donanemab is still under consideration by the FDA for approval.

Next steps

If you or your loved one is worried about new and progressive concerns with memory or thinking, language, or behavior, the first best step is to consult with a doctor and specifically consider a referral to a neurologist. If you are specifically interested in receiving diagnostic assessment and care at UCSF, please contact the UCSF Memory and Aging Center Clinic for guidance on seeking a referral.