Lecanemab is available to administer to patients that meet our internal Lecanemab Review Board requirements. 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.
Donanemab The FDA approved Eli Lilly's drug donanemab, an amyloid-clearing drug similar to lecanemab (Leqembi), citing that the treatment’s benefits outweigh the risks. Donanemab is not yet available to administer at the UW Medicine clinic.
Learn more about lecanemab, a new, FDA-approved medication to slow Alzheimer’s disease. Dr. Michael Rosenbloom, a behavioral neurologist at UW Medicine's Memory & Brain Wellness Center in Seattle explains how the drug works.
What are the currently FDA-approved infusion treatments, lecanemab and donanemab?
Lecanemab is an 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. Lecanemab is available to administer to patients that meet our internal Lecanemab Review Board requirements.
The FDA has also approved donanemab (Kisluna), an amyloid-clearing drug similar to lecanemab, to treat early Alzheimer's disease. Donanemab is delivered in the form of an intravenous (IV) infusion every four weeks. Donanemab is not yet available at the UW Memory and Brain Wellness Center clinic.
How do these treatments 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 and donanemab are antibodies that specifically bind to amyloid beta and allow a person’s immune system to remove the plaques from the brain. Studies with lecanemab and donanemab consistently show marked reduction in the amount of amyloid accumulation in the brain as well as modest slowing of disease progression.
Are amyloid-clearing treatments a cure for Alzheimer’s?
No. Though amyloid-clearing treatments target the underlying biology of Alzheimer’s disease, they are not cures for this condition. 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. Clinical trials of these drugs have shown that they slow clinical decline by 27-29% relative to the placebo group, over 18 months of treatment.
It is also important to point out that amyloid clearing treatments have only been studied in people living with mild 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). Both mild Alzheimer’s disease and MCI are considered early-stage Alzheimer’s disease. 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 amyloid-clearing infusions drugs?
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 amyloid-clearing infusion drugs?
As with any medication, lecanemab or donanemab may have side effects. These medications work 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 these treatments 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 trials demonstrating benefit of these drugs, between 21.5-40% of patients developed ARIA (depending on # of ApoE4 copies), 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, but preliminary studies suggest that patients do not experience cognitive decline afterwards.
The potential risks and benefits of amyloid-clearing infusion drugs must be thoroughly considered in each person individually. Some patients with Alzheimer’s disease may not be appropriate for treatment 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 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 amyloid-clearing therapy is started, patients must receive special monitoring (including brain magnetic resonance imaging [MRI] scans) to screen for ARIA.
Are there certain advantages and disadvantages of lecanemab versus donanemab?
Whereas both drugs have similar effects on disease slowing, lecanemab is administered every 2 weeks whereas donanemab is given every 4 weeks. Donanemab has an increased risk of ARIA, both with and without symptoms, compared to lecanemab.
Are lecanemab and donanemab available to patients now?
Lecanemab is now available to administer to patients that meet our internal Lecanemab Review Board requirements at UW Medicine. Lecanemab is not yet on most formularies and important aspects of insurance coverage (e.g. some private insurance providers) have yet to be clarified. = Amyloid-PET scans are now being covered by Medicare in Washington state. 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. Donanemab is not yet available at the UW Memory and Brain Wellness Center clinic.
What is the controversy about amyloid-clearing infusion treatments?
Not everyone agrees that the efficacy of these drugs 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, but recent data suggest this is a result that occurs with removal of amyloid. The benefit of amyloid-clearing infusion therapy 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 amyloid-clearing infusion treatments cost patients?
The manufacturer is listing the cost of the Lecanemab itself as $26,500 per year and Donanemab at $32,000 per year. The Centers for Medicare and Medicaid have agreed to pay 80% of the cost of the drug itself. Private insurance coverage tends to follow Medicare’s reimbursement process but not for every carrier. Other costs will include MRI scans for monitoring of ARIA and infusion services, both covered by Medicare at the same 80% rate.
What factors will influence who will be treated with amyloid-clearing agents 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.
These drugs are indicated for patients with mild cognitive impairment due to Alzheimer’s disease or very mild Alzheimer’s disease dementia. They have 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. 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 amyloid-clearing infusion therapies are in general 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 an amyloid-clearing treatment?
Clinical investigations have shown that patients receiving this treatment obtain the benefits typically with 18 months of infusions. However, the duration of treatment beyond 18 months has yet to be defined and will require waiting for results of further studies.
What percent of patients who come to the MBWC are appropriate candidates for treatment?
Of everybody that comes into MBWC, 10 or 15% of people are appropriate for this treatment.
How soon do ARIA symptoms start after infusion?
Symptoms typically occur weeks to months after starting the infusion and are most often seen during the first 3 months of treatment.
Can I start on the Leqembi and then switch to the monthly donanemab treatment when it becomes available?
There is no current data to guide switching from one amyloid-clearing agent to another. This decision should be made after having a risk versus benefit discussion with your prescribing physician.
Can you say more about Apoe4 genotype and whether treatment is appropriate for individuals who carry 2 copies?
APOE-E4 carriers, especially those with one or two copies of the APOE-E4 allele, are at a higher risk of not only developing Alzheimer’s disease but also ARIA when treated with anti-amyloid monoclonal antibodies. Studies have shown that individuals carrying one E4 allele have a 2-3 times higher risk, while those with two E4 alleles (homozygous) have an even greater risk (up to 10 times) of developing ARIA compared to non-carriers (E3/E3).
Having two copies of E4 confers the greatest risk of ARIA in patients receiving treatment with amyloid-clearing therapies. However, the decision to treat these patients should be made on an individualized basis. There are no policies at UW where those who are E4/E4 are automatically excluded from treatment.
What other Alzheimer's medications or treatments are on the forefront waiting for FDA approval?
There are ongoing studies evaluating amyloid-clearing agents that more effectively cross the blood brain barriers in treating Alzheimer’s disease. In addition, there are also medications that stimulate the TREM2 receptor to trigger an immune response to clear amyloid in the brain. Finally, there are drugs that are being developed to reduce the amount of neurofibrillary tangles in the brain.