We have entered a new era in the treatment of Alzheimer disease; for the first time, disease-modifying medications targeting the biological hallmarks of the disease are available for clinical use. Lecanemab (also known as Leqembi) is a new FDA-approved medication that removes amyloid plaques from the brain. It has been shown in clinical trials to slow memory decline and help maintain independence in patients with early stages of Alzheimer disease. It is administered intravenously every two weeks.
The Mass General Brigham Alzheimer Therapeutic Program (ATP) offers lecanemab to patients who are interested and appropriate for this new treatment. For additional details about how lecanemab works, its potential benefits, and its risks, please see the Frequently Asked Questions section below.
In the ATP, patients are evaluated to see if they are if they are good candidates for lecanemab treatment. This includes a personalized assessment of the potential risks and benefits of treatment, education about how lecanemab works, and a discussion about whether treatment aligns with their personal values and goals. Safety is the top priority of the ATP; the program is designed to be proactive and responsive to concerns, and careful monitoring for side effects is an essential component of treatment. We also strive to advance the growing clinical and scientific knowledge about anti-Alzheimer therapies, and patients have opportunities to participate in research if they are interested.
The ATP seeks to lead the future of dementia care by providing the highest quality clinical care with disease-modifying therapies, advancing knowledge through research, and educating medical professionals and the public about new advances. Clinical excellence is the primary driving mission of ATP.
Patients undergo an evaluation by ATP clinicians to determine if they may receive lecanemab treatment. This assessment involves gathering information from the patient, their doctors and caregivers (care partners) about symptoms, everyday functioning, and other medical information ( diagnoses, medications, etc.), a short cognitive test, neurological exam, and review of their brain MRI. Specialized Alzheimer disease testing, such as an amyloid positron emission topography (PET) scan or lumbar puncture, is also required, as is a genetic test for apolipoprotein E (APOE). The e4 variant of the APOE gene increases the risk of having treatment-related side effects, including swelling and bleeding in the brain. This risk is highest in patients with two copies of the e4 variant. This treatment-specific evaluation takes place over one to three visits within a few weeks. Some patients may be ineligible for treatment once this data has been reviewed, usually because of concerns about safety or low likelihood of clinical benefit.
Patients eligible for lecanemab and their care partners are provided a clinical overview of lecanemab to inform the decision about whether to receive the medication. This discussion includes how lecanemab works, its potential benefits and side effects, safety planning and monitoring, and an overview of the ATP structure and how to contact our team. Risk assessments are personalized based on APOE genetic testing results and other clinical factors. We strive to understand patient values, priorities, and goals of treatment, and do our best to ensure treatment works towards these goals. Personalized and well-informed decisions are crucial in helping our patients achieve the best outcome.
Infusion Visits
Lecanemab infusions are administered every two weeks at designated infusion centers. The infusion takes place over 60 minutes, with an observation period after each infusion. The observation window is longest after the first few infusions and shortens with later infusions.
MRI Monitoring
At least three MRIs are required during the first 6 months of treatment, always after the 4th, 6th and 13th infusions. These MRIs screen for areas of swelling and/or bleeding in the brain, collectively known as amyloid-related imaging abnormalities (ARIA), which can occur in patients taking lecanemab. If patients report new symptoms, additional MRIs may be recommended.
Phone Check-Ins
Patients receive periodic phone calls from the ATP staff for symptom monitoring. These may take place before (e.g., screen for symptoms suggestive of ARIA) or after an infusion (e.g., screen for symptoms suggestive of an infusion reaction). Patients are always encouraged to proactively reach out to the ATP with new symptoms or if there are other changes in their health or medications.
Follow-Up Visits
In addition to infusion visits every 2 weeks, ATP patients will follow up in the clinic for check-up every six months. Additional office visits may be needed in some cases.
ATP Clinic Care Model
The ATP is staffed by a rotating team of neurologists with subspecialty expertise in Alzheimer disease. Once a patient has established care within the ATP, there are multiple ways to contact our team, including telephone during work hours and patient portal messaging; for emergencies, the ATP on-call clinician be reached via direct page 24 hours per day, 7 days per week. ATP provides specialized care specifically related to lecanemab. Alzheimer care that does not directly relate to lecanemab treatment must be provided by the patient’s referring clinician.
The FDA has set guidelines on who will be eligible to receive this treatment, summarized in the FDA label. Only individuals who meet these guidelines will be evaluated to receive it; for safety reasons, some individuals will be ineligible to receive this treatment. Experts in the field have also published an article documenting appropriate use recommendations. Broadly speaking, it is approved for patients with early-stage cognitive impairment due to Alzheimer disease who are otherwise free of contraindications. Early-stage cognitive impairment is defined as mild cognitive impairment: cognitive decline that does interfere with a person’s independent daily functioning, or mild dementia: cognitive impairment that causes a loss of independence in complex daily activities (e.g., paying bills, driving, managing medications) but not for basic daily activities (e.g., bathing, feeding, dressing). To be diagnosed with Alzheimer disease for the purposes of lecanemab eligibility, a specific biomarker test must be performed, which includes an amyloid PET scan or a lumbar puncture for tests of amyloid and tau.
Some patients and families may decide they do not want to receive this medication for medical, personal, or other reasons. The ATP will discuss alternative care options, including clinical trials.
Lecanemab works by lowering the level of beta-amyloid protein in the brain. This approach does not stop the disease progress nor lead to improvement in symptoms or functional abilities. Rather, it slows the rate of cognitive and functional decline. In the Phase 3 research study, the group treated with lecanemab had a reliable slower decline on cognitive tests and questionnaires assessing functioning in activities of daily living than the group that received a placebo (an approximately 5-month saving over the 18 months of the trial, on average). Not all experts agree on whether this represents a clinically significant difference.
The magnitude of the effect is likely different from person to person.
The Centers for Medicare and Medicaid Services (CMS) has indicated that coverage will be provided to Medicare beneficiaries if they are enrolled in an approved Alzheimer Patient Registry. The medication costs approximately $26,500 a year. The exact cost to beneficiaries will vary by different insurance coverage plans. For example, individuals with Original Medicare will pay the standard 20% coinsurance of the Medicare-approved amount for lecanemab once they meet their Part B deductible, whereas patients with supplemental Medicare plans may have much of this deductible covered. Patients may also be responsible for some costs associated with infusions, MRI scans, health care provider appointments, and other aspects of treatment. Some private health insurance plans have announced plans to cover lecanemab with prior authorization, whereas other plans have not yet provided details.
Patient registries will collect information from providers to help ensure appropriate patient selection and use of anti-amyloid antibody treatments for AD. Data about patient outcomes and safety will be of critical importance and will help us make decisions about future treatment options.
To be considered for treatment, patients must be evaluated for cognitive changes and receive a diagnosis of mild cognitive impairment due to AD or mild AD dementia. The following elements must be completed by a primary care doctor, neurologist, psychiatrist, or other referring provider prior to referral:
Lecanemab is given every 2 weeks by a healthcare provider through a needle placed in the patient’s vein (intravenous (IV) infusion) in their arm. Each infusion will last about 1 hour, followed by a period of observation. The MGB ATP will be responsible for providing the patient a schedule of infusions. Infusions will be given at Mass General Brigham hospitals and satellite facilities. At the Brigham, infusions will take place at the Faulkner Hospital or the Main Campus. At Mass General, infusions take place at the Medical Infusion Center.
Lecanemab is currently given every two weeks for a minimum of 18 months. Additional information is being collected on the treatment period to guide decision-making once these 18 months are completed. In addition to infusion visits and regularly scheduled visits with their referring providers, patients receiving lecanemab in the ATP will be seen in the ATP clinic every 6 months (or more often, as indicated) and will have safety MRIs completed after their 4th, 6th and 13th infusion treatments (plus additional MRIs as indicated).
There are several reasons that may lead to stopping lecanemab before the treatment is completed. Examples include severe treatment-related side effects (e.g., swelling and/or bleeding in the brain) or the development of contraindication to treatment, such as being diagnosed with an unstable medical or neurologic condition, needing to start a blood thinner, or progression to moderate stages of dementia. Many other circumstances are possible, and ATP will address them on a case-by-case basis. Patients can always voluntarily stop taking lecanemab at any time during treatment.
Lecanemab can cause small areas of swelling or bleeding in the brain called amyloid related imaging abnormalities (ARIA). ARIA is usually asymptomatic and detected only by monitoring MRI scans. In the phase 3 study investigating lecanemab, only 2.8% of subjects receiving lecanemab had symptoms due to ARIA. Most symptoms were mild, involving temporary symptoms including headache, confusion, dizziness, changes in vision, nausea, or difficulty walking, and were temporary. However, ARIA-related swelling occurred in 12.6% of subjects receiving lecanemab, and 8.4% of subjects had both swelling and bleeding, often without producing symptoms. Patients will therefore need to be monitored with MRIs (usually once per month) until it resolves (usually within 6 months).
Rarely, ARIA can cause seizures or larger areas of inflammation and/or bleeding in the brain. The risks of ARIA, symptomatic ARIA, and serious symptomatic ARIA leading to hospitalization are highest in people carrying 2 copies of the APOE ε4 gene. In the phase 3 study, the rates of symptomatic ARIA with lecanemab treatment were 9.2% in participants with 2 APOE4 genes, 1.7% in participants with 1 APOE4 gene, and 1.4% in participants who did not carry an APOE4 gene. The rates of serious symptomatic ARIA were 2.1% in participants with 2 APOE4 genes, 0.4% in participants with 1 APOE4 gene, and 0.7% in participants who did not carry an APOE4 gene.
ARIA most often occurs within the first 6 months of treatment. We recommend against long distance and/or extended-duration travel during this higher-risk period.
In the first part of the lecanemab phase 3 trial where 1,795 participants received either active drug (lecanemab, 898 participants) or placebo (salt water, 897 participants) over 18 months, there was no difference in the number of participants who died (6 receiving lecanamb and 7 receiving placebo). Following this part, participants were offered to continue in an extension (open label portion) of the study where everybody received active drug (lecanemab) and nobody received placebo (salt water). During this extension, 3 participants (out of about 900) died from side effects thought to be due to lecanemab Two of the deaths were related to brain hemorrhages (bleeding), one occurring in a participant on anticoagulation (a blood thinner), the other in a patient who received tissue plasminogen activator, a medication used to break down blood clots in patients with acute stroke. The third death occurred in a patient homozygous for APOE4 (with 2 copies of the APOE4 gene) who developed swelling and bleeding in the brain similar to a condition involving excessive amyloid protein in blood vessels in the brain with associated inflammation. Under the ATP protocol, patients on anticoagulation will not be eligible to receive lecanemab, and thrombolytic (clot-busting) medications are to be avoided. A key purpose of the screening MRI prior to treatment is to identify findings such as small areas of bleeding (microhemorrhages) and other features suggesting amyloid protein in blood vessels that would lead to a higher risk of serious ARIA. Also, all patients will have APOE genotyping prior to deciding about treatment with lecanemab. This will allow us to identify patients with 2 copies of the APOE4 gene, who are at higher risk for developing side-effects.
Donanemab is another anti-amyloid monoclonal antibody for removal from the brain. It was approved by the FDA on July 2, 2024.
Donanemab is administrated intravenously every 4 weeks for 18 months, although it can be discontinued prior to 18 months once amyloid is successfully cleared from the brain. In a recently published clinical trial, donanemab was shown to reduce the progression of cognitive decline and maintain independence in everyday activities. Click here to review the full results.
The main side effects of donanemab are swelling and bleeding in the brain discovered on a brain MRI, collectively known as amyloid related imaging abnormalities (ARIA). ARIA occurred in 37% of trial participants receiving donanemab, although most ARIA did not cause symptoms. Symptoms due to ARIA developed in 6% of trial participants treated with donanemab. Serious symptoms of ARIA occurred in 1.6% of people on donanemab. ARIA was more common in people with the e4 variant of the APOE gene.
Donanemab joins lecanemab (Leqembi) as the 2nd FDA-approved anti-amyloid antibody treatment approved for Alzheimer disease in the past year. Although the medications have a similar mechanism of action, there are advantages and disadvantages to each.
The MGB Alzheimer Therapeutic Program (ATP) is enthusiastic about the FDA approval of donanemab and is seeking to add this medication to the MGB hospital formularies as quickly as possible in our preparations to deliver the medication. Like all new medications, donanemab will be carefully reviewed by the MGB Pharmacy and Therapeutics Committee, a process which can take weeks to month. If/when donanemab is approved by this committee, members of the ATP will work with eligible patients to discuss the pros and cons of treatment with lecanamab vs donanemab.
We continue to accept new referrals to determine eligibility for anti-amyloid therapies and to initiate and oversee treatment with them.
Aducanumab was studied in two phase 3 studies, that, for various reasons did not provide sufficient data to definitively determine its effectiveness for slowing symptoms of AD. It was granted accelerated approval from the FDA (rather than full approval) and is NOT covered by Medicare.
While the phase 3 study provided a preliminary analysis of selected subgroups of subjects with AD, it was not designed or powered to provide conclusive results about the effectiveness or side effects of lecanemab in these subgroups. Additional data from more subjects will be helpful to answer these important questions. This is one purpose of the registry noted above.
Deciding to start treatment is a decision each patient should make with their care partners and physician. The ATP will continue to be a resource for patients who decide not to receive treatment and will review alternative options such as research and supportive care.
Yes. Prior participation in clinical therapeutic research studies does not make patients ineligible to receive lecanemab, provided the other eligibility criteria are satisfied.
At present, most if not all clinical therapeutic studies investigating potential new treatments for AD do not allow concomitant treatment with lecanemab. This could change in the future. We recommend that patients speak with their current provider and/or contact the Center for Alzheimer Research and Treatment (CART) if there are questions about whether pursuing treatment with lecanemab or enrolling in a clinical therapeutic research study is the best option.
Patients who are currently enrolled in a clinical therapeutic study or an observational study are encouraged to contact their research site about the potential impact of pursuing treatment with lecanemab on their ongoing participation in the study.
Donanemab Receives Full FDA Approval
The US Food and Drug Administration (FDA) approved donanemab (Kinsula) on July 2nd, 2024, for the treatment of early stages of Alzheimer disease. Donanemab is a monoclonal antibody that targets beta-amyloid, one of the abnormal proteins in Alzheimer disease, for removal from the brain. It is administrated intravenously every 4 weeks for 18 months, although it can be discontinued prior to 18 months once amyloid is successfully cleared from the brain. In a recently published clinical trial, donanemab was shown to reduce the progression of cognitive decline and maintain independence in everyday activities. Click to review publication of trial data.
The main side effects of donanemab are swelling and bleeding in the brain discovered on a brain MRI, collectively known asamyloid related imaging abnormalities (ARIA). ARIA occurred in 37% of trial participants receiving donanemab, although most ARIA did not cause symptoms. Symptoms due to ARIA developed in 6% of trial participants treated with donanemab. Serious symptoms of ARIA occurred in 1.6% of people on donanemab. ARIA was more common in people with the e4 variant of the APOE gene.
Donanemab joins lecanemab (Leqembi) as the 2nd FDA-approved anti-amyloid antibody treatment approved for Alzheimer disease in the past year. Although the medications have a similar mechanism of action, there are advantages and disadvantages to each.
The MGB Alzheimer Therapeutic Program (ATP) is enthusiastic about the FDA approval of donanemab and is seeking to add this medication to the MGB hospital formularies as quickly as possible in our preparations to deliver the medication. Like all new medications, donanemab will be carefully reviewed by the MGB Pharmacy and Therapeutics Committee, a process which can take weeks to month. If/when donanemab is approved by this committee, members of the ATP will work with eligible patients to discuss the pros and cons of treatment with lecanamab vs donanemab.
We continue to accept new referrals to determine eligibility for anti-amyloid therapies and to initiate and oversee treatment with them.
To be determined - please check back!
For those concerned about memory and thinking but do not have a diagnosis:
For those not eligible for this treatment and looking for other options. Learn about research opportunities that may be available:
Brigham and Women’s Alzheimer Therapeutic Program (ATP) Clinic
Massachusetts General Hospital Alzheimer Therapeutic Program (ATP) Clinic
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