On July 6, 2023, the Federal Drug Administration (FDA) approved the Alzheimer’s drug Leqembi (lecanemab) for the treatment of Alzheimer’s disease in the mild cognitive impairment and mild dementia stage.
The Penn Memory Center and Penn Medicine have developed a plan for prescribing and administering Leqembi. The plan is currently being piloted, and we expect to expand it to qualified Penn Memory Center patients by the end of 2023. To schedule an appointment with the Penn Memory Center, please contact our clinic at 215-662-7810.
On this page are common questions about Leqembi and Penn Medicine’s answers. Click here to learn more about other disease-modifying therapies.
An Update on Anti-Amyloid Therapies for Alzheimer’s Disease
What is Leqembi (lecanemab)?
Leqembi is a drug developed by BioArctic AB, Biogen, and Eisai Co., Ltd. Leqembi has been found to slow cognitive decline in people living with early-stage Alzheimer’s disease. Lecanemab is the scientific name of the drug. It is marketed as Leqembi.
How does Leqembi work?
Patients with Alzheimer’s disease have a build-up of a protein, amyloid-beta, in their brains. These are commonly called “amyloid plaques.” Lecanemab is a human monoclonal antibody synthesized in a laboratory that selectively targets amyloid-beta.
Studies show that lecanemab reduces the build-up of amyloid-beta. It also slows the declines in a person’s ability to carry out day-to-day activities.
How is Leqembi administered?
The drug is given as an hour-long intravenous (IV) infusion every two weeks.
How much does Leqembi cost?
Eisai has set Leqembi’s annual price at $26,500.
We are awaiting guidance from Centers for Medicare and Medicaid Services (CMS) and the insurance companies on costs.
Who will be eligible for Leqembi?
Individuals with mild cognitive impairment (MCI) or mild-stage dementia due to Alzheimer’s disease are eligible to receive Leqembi. This drug is not safe for people who are on blood thinners.
How is it determined if I am eligible for Leqembi?
Several tests inform the determination:
- A history and assessment of cognition and day to day function: This assessment, done by your primary care provider or Alzheimer’s disease specialist, determines if you have mild cognitive impairment or mild-stage dementia
- Magnetic Resonance Imaging (MRI) scan of the brain: This scan determines if you have evidence of small areas of blood in the brain. These are called micro-hemorrhages. They are common in persons with Alzheimer’s Disease. They may increase the risks of Leqembi. These risks are discussed below.
- Blood work: Blood work helps to determine if there are other causes of cognitive impairments other than Alzheimer’s Disease
- Genetic testing : Your provider will order genetic testing for a gene called APOE. This test, completed using a sample of blood or saliva, assesses if you have a gene called “e4.” This gene is associated with a greater chance of the risks of treatment: micro-hemorrhages and edema in the brain. These risks are discussed below.
- A test for the presence of beta-amyloid in the brain: this test can be a Positron Emission Tomography (PET) Scan or a spinal fluid sample obtained using a lumbar puncture
What are the potential side effects of Leqembi?
The main side effects of Leqembi are microscopic hemorrhages and edema in the brain. These are described with the term ARIA which is an abbreviation for “Amyloid-Related Imaging Abnormalities.” These are abnormalities are caused by inflammation around the small blood vessels in the brain. This can cause swelling of the brain and microhemorrhages.
The FDA has labeled Leqembi with a “Warning” about this risk. This warning emphasizes that the risk of ARIA is associated with have an e4 gene. This gene-risk association is discussed below.
In a study of 1,800 participants, participants receiving the Leqembi were twice as likely to experience brain bleeding and swelling than those receiving the placebo.
In most pateints, ARIA is asymptomatic. It is detected using a MRI scan. About 25% of persons with ARIA have mild symptoms (~3% of all treated) and a small number have more serious and permanent neurological outcomes (~1%).
Other side effects include hypersensitivity reactions, headaches, diarrhea and falls.
What is the APOE gene?
The APOE gene has a well-documented association with an increased chance of developing Alzheimer’s disease. It is called a “susceptibility gene.” The APOE gene has three different versions or forms: e2, e3, and e4. Each individual has a combination of two of these forms.
The APOE gene is associated with two risks. One is the risk of developing Alzheimer’s disease and the other is the risks of ARIA. Below we discuss the first risk.
First, certain patterns of the APOE gene increase the risk Alzheimer disease. The e4 form is associated with earlier onset and in people who have the e4 allele and Alzhemer’s disease their symptoms can be more notable. Two copies of e4 causes a higher risk than one copy of e4. The general population lifetime dementia risk is about 10-12%. While the risk percentages vary based on the population studied, Qian et al. (2017) found a 31-40% lifetime risk for people with two copies of e4 to develop AD. However, there are many people who develop AD without having one or two e4 alleles, and there are people who have one or two e4 alleles who never develop dementia.
Some APOE gene variants are associated with risks for other conditions such as cardiovascular disease, ischemic stroke, increased impairment after concussion, age-related hearing loss, and age-related macular degeneration.
The APOE gene is not the only gene associated with dementia. If you have a family history of dementia, especially with onset at a young age (<65yo), it is important to share this information with your physician as a referral may be made to genetic counseling.
Why does APOE status matter for Leqembi prescription?
Individuals who receive Leqembi and who have one or two copies of the e4 allele of APOE have an increased risk of ARIA (Amyloid-Related Imaging Abnormalities). These are abnormalities caused by inflammation around blood vessels that can lead to local swelling of the brain and microhemorrhages in the brain. This increased risk was relatively mildly increased in carriers of one copy. It is significantly higher in those with two copies of e4.
These are abnormalities caused by inflammation around blood vessels that can lead to local swelling of the brain and microhemorrhages in the brain. For most persons, ARIA is asymptomatic and detected with MRI imaging. About 25% of individuals treated with Leqembi have mild symptoms and a small number have more serious and permanent neurological outcomes.
If I have one or two copies of e4, can I still be prescribed Leqembi (Lecanemab)?
There is a mildly increased risk of side effects for individuals with one copy of the APOE e4 while there is a much higher risk in individuals with two copies. You and your physician should discuss all possible risks and benefits of Leqembi before making your decision about taking Leqembi. Knowing your APOE status will help you and your physician in this decision-making process.
In addition to the infusion appointments every other week, what other requirements are there to receive Leqembi?
Patients must receive a Magnetic Resonance Imaging (MRI) scan of the brain after the 5th, 7th, and 14th infusions to ensure there is no brain bleeding and swelling.
Patients with Medicare coverage will also need to consent to data collection as part of Medicare’s Coverage with Evidence Development (CED) policy.
Where can I go for more information?
For specific questions regarding your condition or the condition of a loved one, please contact your physician or make an appointment with the clinicians at the Penn Memory Center. For general questions you can reach the Penn Memory Center at pennmemorycenter@pennmedicine.upenn.edu.
Leqembi News:
- Are we there yet with PET? Penn Memory Center
- FDA grants accelerated approval for Alzheimer’s disease treatment FDA.gov
- FDA gives green light to Leqembi, aka lecanemab Alzforum
- Dr. Karlawish answers common questions about Leqembi SciLine
- Dr. Karlawish warns of lecanemab safety concerns Science
- New Alzheimer’s Drug Shows Positive Results but Side Effects, The Wall Street Journal ($)
- Alzheimer’s drug shows modest success slowing declines in memory, thinking, NPR
- The science behind lecanemab, BioArtic AB
- APOE genotyping will play a major role in lecanemab prescribing the clinical, ethical, and financial ramifications, Neurology Today
- Shrunken FDA Advisory Committee Is Unanimous: Leqembi Works, Alzforum Networking For A Cure
- There’s finally a fully approved Alzheimer’s drug – but getting it won’t be easy, TIME