What the FDA Approval of Lecanemab Means for Patients and Families: A Q&A with MBWC Clinicians

July 07, 2023

Science Updates, New FDA Drug Approvals, Care & Treatment , News

On July 6, 2023, the U.S. Food and Drug Administration (FDA) fully approved lecanemab (brandname Leqembi) to treat very early Alzheimer’s disease.  Our clinic team at the Memory and Brain Wellness Center would like to share some information about this newest therapy with our patients and community.

Lecanemab is not yet clinically available at UW Medicine MBWC, but we are hoping to make it available soon. We have joined a national clinical Registry (ALZ-NET) which will allow us to participate in the Medicare coverage of this treatment.  We will continue to update the UW Medicine community on our progress. However, the UW MBWC, home of the Alzheimer's Disease Research Center, is conducting research on the potential benefits of lecanemab for the prevention of Alzheimer’s disease with the National Institutes of Health-funded ​​AHEAD Study.  Individuals interesting in participating can contact our research team.

What is lecanemab? 

Lecanemab is a newly approved medication for the treatment of Alzheimer’s disease and is marketed under the brand name Leqembi. Lecanemab is administered in the form of an intravenous (IV) infusion every 2 weeks, for a period of up to 18 months.


How does lecanemab work?

Amyloid-beta protein accumulates in the form of plaques in the brains of people with Alzheimer’s disease. This amyloid accumulation is thought to contribute to the cognitive decline seen in the disease. Lecanemab is an antibody that specifically binds to amyloid beta and allows a person’s immune system to remove the plaques from the brain. Studies with lecanemab consistently show marked reduction in the amount of amyloid accumulation in the brain.


Is lecanemab a cure for Alzheimer’s?

No. Though lecanemab is one of the first FDA -approved treatments to favorably affect the underlying biology of Alzheimer’s disease, it is not a cure. According to the FDA, the reduction in amyloid plaques produced by this medication is reasonably likely to lead to a slowing in the clinical decline due to the disease.  In the clinical trial that led to FDA approval, clinical decline was slowed by 27% relative to the placebo group, over 18 months of treatment.

It is also important to point out that lecanemab has only been studied in people living with early Alzheimer’s disease and mild cognitive impairment (MCI) due to Alzheimer’s who showed evidence of a buildup of amyloid plaques in the brain (proven by biomarkers in spinal fluid or PET scans). The therapy has not yet been tested on people with moderate or more advanced cases of Alzheimer’s or on individuals with other forms of dementia.


What type of diagnostic testing is required before starting this medication?

A trained physician should confirm the presence of amyloid plaques in the brain before prescribing this anti-amyloid plaque treatment. The FDA requires an amyloid protein test to demonstrate that Alzheimer’s disease is present. This can be done by collecting spinal fluid through a lumbar puncture (“spinal tap”) procedure to test for amyloid or by an amyloid PET brain scan. Confirmatory tests like these make sure that the patient has brain amyloid before undergoing this specialized therapy. Before considering this 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 University of Washington Memory and Brain Wellness Center is one of many centers with expertise in diagnosing Alzheimer’s disease.


What are potential side effects of lecanemab? 

As with any medication, lecanemab may have side effects.  Lecanemab works by helping the immune system remove amyloid deposits from the brain.  In Alzheimer’s disease, amyloid protein may also accumulate in the walls of small blood vessels in or on the surface of the brain, and some  patients may experience an exaggerated immune response in the brain.  For these reasons, the action of lecanemab may cause blood vessel leakiness leading to localized brain swelling, bleeding in the brain, or both. These side effects can be seen using MRI imaging of the brain and are collectively called amyloid-related imaging abnormalities (ARIA). In the clinical trial demonstrating benefit of lecanemab, about 13% of patients developed ARIA, though most did not have any symptoms from ARIA, and most ultimately completed the course of medication.  A few percent of patients develop a more serious degree of ARIA and cannot continue the medication. Long term effects of ARIA are not well studied.

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 concerns about their individual balance of possible risks and benefits from treatment. Some patients are not eligible because they require blood thinners, or have other particular medical conditions which were excluded from the original studies.  It is strongly recommended to perform a genetic test for the APOE gene type, since a small number of patients have a higher risk of ARIA depending on their APOE genotype.  Additionally, before and after lecanemab is started, patients must receive special monitoring (including brain magnetic resonance imaging [MRI] scans) to screen for ARIA.


Is lecanemab available to patients now?

No, but availability is expected to be coming over the next several months, based on the new full FDA approval and the indication that Medicare will cover lecanemab under specific conditions.  Lecanemab is not yet on most formularies and important aspects of insurance coverage (e.g. private insurance providers) have yet to be clarified.  We are also awaiting clarity on coverage for amyloid PET scans, which are currently not generally covered by Medicare. Medicare is covering this drug when a physician and clinical team participates in the collection of evidence about how these drugs work in the real world, also known as a registry. 

Are there alternatives to lecanemab?

At this time lecanemab is the only “disease-modifying” treatment for Alzheimer’s disease that is approved for clinical use. Another medication in the same class of anti-amyloid antibodies, called donanemab, has also had very promising results in clinical trials, and is expected to be considered by the FDA this year.  We think that lecanemab and donanemab, which have the same basic mechanism of action, are probably similarly effective. Aducanumab is another “disease-modifying” treatment that received accelerated approval by FDA, but the drug will only be covered when used in the context of clinical trials.  Studies show that this drug is less effective at slowing decline and has an increased risk of ARIA side effects compared to lecanemab.


What about lecanemab at UW Medicine?

UW Medicine Neurosciences Institute and its Memory and Brain Wellness Center are currently working diligently to bring lecanemab to the UW formulary, and to establish capacity and processes for safely and effectively administering lecanemab to our patients. We are identifying appropriate candidates and initiating the needed biomarker and baseline imaging tests for them.  We have joined a national clinical Registry (ALZ-NET) which will allow us to participate in the Medicare coverage of this treatment.  We will continue to update the UW Medicine community on our progress.

What is the controversy about lecanemab?

Not everyone agrees that the efficacy of lecanemab is enough to justify cost, burden to patients, and risk of ARIA.  Long term effects of ARIA are not clear.  There are also reports of overall brain shrinkage in patients administered anti-amyloid antibodies including lecanemab, and the significance of this finding is unclear.  The benefit of lecanemab beyond the 18 month clinical trial period is not yet well-studied. Most of these questions will be clarified by more experience with the medication.  Medicare is thus making participation in a clinical registry for “Clinical Evidence Development” a condition of coverage of this medication.


How much will lecanemab cost patients?

The manufacturer is listing the cost of the medication itself as $26,500 per year. How the Centers for Medicare and Medicaid Services (CMS) decides to cover lecanemab will make a big difference in out-of-pocket costs, which may be less. Private insurance coverage will probably become clear only after CMS makes its determination. Other costs will include MRI scans for monitoring of ARIA, and infusion services.


What factors will influence who will be treated with lecanemab at the Memory and Brain Wellness Center?

There are two sets of factors – those defining the group of patients that are eligible for the medication and likely to benefit, and practical issues as eligible patients consider the logistics, costs, risks, and benefits of the treatment.

In general, lecanemab is indicated for patients with mild cognitive impairment due to Alzheimer’s disease, or very mild Alzheimer’s disease dementia. The medicine has not been tested for benefit or risk in asymptomatic persons, in those with moderate to severe Alzheimer’s disease, in mixed vascular and Alzheimer’s disease dementia, or in any other disease-causing memory loss and cognitive impairment. In order to be sure of a diagnosis of Alzheimer’s disease, one must have an Alzheimer’s biomarker test on spinal fluid or by PET scan showing amyloid in the brain. Because of possible side effects on small blood vessels in the brain causing leakage of fluid (edema) or blood (microhemorrhage), patients must be able to undergo MRI scans and must not be taking blood thinners.

Factors that are important for eligible patients to consider include: 1) understanding that the effectiveness of lecanemab in general is modest, and might be hard to notice in any given individual; 2) understanding the risk of brain edema and microhemorrhage; 3) understanding that this is a twice monthly IV infusion that will require visits to a health care facility;  4) considerations of cost.


How long do patients need to take lecanemab?

We do not yet know how long patients need to take the medication. The duration of therapy has yet to be defined, and it will require waiting for results of further studies. 


Further reading

Prescribing Information for Leqembi (Leqembi.com)

Statement on Broader Medicare Coverage for Leqembi available following FDA traditional approval (CMS.gov)

NIA statement on the report of Lecanemab reducing cognitive decline in Alzheimer’s clinical trial (National Institute on Aging)

FDA Announcement: FDA grants accelerated approval for Alzheimer’s disease treatment (FDA)

Research participant’s insights on Lecanemab and other stories (Being Patient)

Lecanemab approved for treatment of early Alzheimer’s disease (Alzheimer’s Association)

Seattle Times coverage: Explainer: New drug slows Alzheimer’s but comes with caveats (Seattle Times)