On January 6, 2023, the Food and Drug Administration (FDA) granted “accelerated approval” to lecanemab (marketed as Leqembi™) for the treatment of people in the earliest symptomatic stages of Alzheimer’s disease. This medication is one of the first disease-modifying therapies approved for the treatment of Alzheimer’s disease in the United States.

Lecanemab is not yet clinically available at UCSF. UCSF is conducting research on the potential benefits of lecanemab for the prevention of Alzheimer’s disease as part of the National Institutes of Health-funded AHEAD Study. Individuals who may be interested in participating in this study at UCSF contact our clinical trials team.

Additional information about lecanemab and its approval

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.

What does “accelerated approval” mean?

Lecanemab has an “accelerated approval” from the FDA, which differs from the FDA’s traditional full approval. The FDA sometimes grants this special accelerated approval to enable earlier access to medications for serious diseases with limited alternative treatment options. Accelerated approval is occasionally granted to drugs that clearly improve laboratory or imaging measures of a disease, even if that drug’s effects on disease symptoms are not yet firmly established. Lecanemab’s accelerated approval was based on brain imaging studies which confirmed its ability to remove amyloid beta plaques from the brain. Moving forward, the FDA will further consider the results of a recent large clinical trial that established lecanemab’s clinical benefit on the earliest symptoms of Alzheimer’s disease. The results of this new large trial were announced only in November 2023 and therefore were not included in the current FDA decision, which was based on earlier-stage trials of the drug. Based on their review, the FDA may decide to grant full approval, which is the traditional way that drugs are approved for patient use. This process is expected to take about 6 months.

Who might receive lecanemab if it becomes clinically available at UCSF?

Lecanemab is not clinically available for any UCSF patients at this time. Under its current FDA label, lecanemab should only be considered for use in people who have a firmly established 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. Lecanemab 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). 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 or an amyloid beta positron emission tomography (PET) scan of the brain. Additionally, people who carry a specific gene version called APOE-ε4 experience a higher risk of side effects from lecanemab. Testing for this gene will be recommended for everyone who is being considered for lecanemab treatment.

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. People who carry a specific gene version called APOE-ε4 are particularly susceptible to developing ARIA, especially when they have two copies of this gene version. 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. 

Anticoagulation: 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 least one person 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?

Aducanumab (marketed as Aduhelm) is a drug with a similar mechanism to lecanemab, but it targets a different version of amyloid beta and may be less effective at removing amyloid beta at its recommended dose. Two large trials of aducanumab in early symptomatic Alzheimer’s disease were discontinued prematurely, and one trial did not show a benefit in symptoms. Whereas aducanumab currently holds an accelerated approval from the FDA, the controversy surrounding this approval resulted in a formal congressional inquiry. The scope of clinical use of Aduhelm remains limited, given its unclear evidence of clinical benefit and lack of coverage by most insurers.

Next steps

Clinic providers at UCSF have not started prescribing lecanemab or similar drugs. UCSF is currently determining how lecanemab might be considered for use in appropriate patients already receiving care at the UCSF Memory and Aging Center.

Currently, the Centers for Medicare & Medicaid Services (CMS) does not cover treatment for medications like lecanemab outside of research studies. Given lecanemab’s recent evidence of benefit in slowing early Alzheimer’s disease symptom progression, CMS may elect to update its policy on drugs in this class in the next year. We don’t yet know when CMS will perform its review for lecanemab, but aspects of this review are contingent on the FDA’s ongoing consideration of a possible full approval (see discussion of accelerated approval above). Additionally, most private insurers have not yet weighed in on coverage decisions for lecanemab.

UCSF is conducting research on the potential benefits of lecanemab for the prevention of Alzheimer’s disease as part of the National Institutes of Health-funded AHEAD Study. Individuals who may be interested in participating in this study at UCSF can contact our clinical trials team here.