Alzheimer’s disease - Lecanemab
Lecanemab is approved to treat adults in the early stages of Alzheimer’s disease who have one or no copies of the apolipoprotein E4 gene (ApoE4). A person can have no copies, one copy or two of this gene. Approximately 15% of those diagnosed with Alzheimer’s have two copies of this gene, known as homozygous patients, and are at increased risk of developing Alzheimer’s disease, while people with one copy also have an increased risk.
In the main clinical trial of 1,795 people with early Alzheimer’s disease, including patients with mild cognitive impairment or mild dementia and confirmed presence of amyloid beta pathology, ApoE4 homozygous patients who received lecanemab were at higher risk of developing Amyloid Related Imaging Abnormalities (ARIAs), which are most commonly seen as temporary swelling in one or more areas of the brain (ARIA-E) or small spots of bleeding in or on the surface of the brain (ARIA-H).
Whilst most ARIA events were only seen on a brain scan and did not cause any symptoms, in a small number of patients serious symptoms occurred. The risk of symptomatic, serious radiographic imaging and recurrent ARIA events were higher in ApoE4 homozygous patients compared with those with one or no copies of the gene. This increased risk was 45% in the homozygous group, 19% in the heterozygous group and 13% in the non-carriers, compared to 22%, 9% and 4% respectively in the placebo group.
In addition, the level of benefit in the ApoE4 homozygous patients with 2 copies of the ApoE4 gene, was uncertain compared with ApoE4 heterozygotes, those who have one copy of the ApoE4 gene or non-carriers.
The CHM therefore advised that the risk benefit of lecanemab was favourable in the patients who were ApoE4 non-carriers or heterozygous but not in the homozygous group, and that testing for the APOE4 gene should be carried out before treatment.
Use of lecanemab in patients who are on anticoagulants (blood thinners, including warfarin) or have been diagnosed with cerebral amyloid angiopathy (CAA) on MRI before starting treatment is contraindicated as the risks in these patients are considered to outweigh the benefits.
Lecanemab is a monoclonal antibody which binds to a protein called amyloid beta In Alzheimer’s disease, clumps of amyloid beta protein form plaques in the brain. Lecanemab works by binding to these clumps and reducing them, therefore slowing the progression of the disease.
Lecanemab treatment, a 10mg/kg dose, is administered intravenously in a healthcare setting every two weeks, with each infusion lasting approximately one hour, and it is given to the patient under the supervision of a healthcare professional. If well tolerated, treatment continues until a patient progresses beyond mild Alzheimer’s disease to moderate disease.
Patients in the clinical trial were given either lecanemab (at a dose of 10 mg/kg, once every two weeks) or placebo. At 18 months lecanemab demonstrated a statistically significant reduction in clinical decline when compared with the placebo. A statistically significant reduction in amyloid beta plaque levels in the brain for lecanemab, compared to placebo, was also seen.
The most common side effects of the medicine are infusion-related reactions (which can cause fever and flu-like symptoms), headaches and ARIA.
As with any medicine, the MHRA will keep the safety and effectiveness of lecanemab under close review. To promote safe and effective use and keep the safety and efficacy of lecanemab under close review, initiation of treatment in any patients will be through a central registration system implemented as part of a controlled access programme.
A controlled post-authorisation safety study will be conducted to investigate the safety and benefit-risk profile of lecanemab in routine clinical practice, particularly in relation to incidence and severity of ARIAs and intracerebral haemorrhage, and long-term safety.
Further Information
Lecanemab (Leqembi) FAQs
Is lecanemab a cure for Alzheimer's and all other dementia?
No. Lecanemab is not a cure, but it is the first traditionally approved treatment that addresses the underlying biology of Alzheimer's and changes the course of the disease in a meaningful way for people in the early stages. Another treatment, aducanumab (Aduhelm®), has received accelerated approval.
By slowing progression of the disease when taken in the early stages of Alzheimer's, individuals will have more time to participate in daily life and live independently.
Who should take this drug?
The prescribing information specifies that lecanemab is appropriate for people with early Alzheimer's with confirmation of elevated beta-amyloid. The treatment was studied in people living with mild Alzheimer's dementia and MCI due to Alzheimer's who showed evidence of a buildup of beta-amyloid plaques in the brain. The therapy has not been tested on people with more advanced stages of Alzheimer's or those without clinical symptoms.
Will this drug restore memories or cognitive function that has been lost?
There is no evidence this or any treatment can restore or reverse lost memories or cognitive function due to Alzheimer's disease.
What type of diagnostic test are required?
There is no single diagnostic test that can determine if a person has Alzheimer's disease. Physicians use a variety of approaches and tools to help make a diagnosis. To diagnose Alzheimer's, physicians may use medical history, mental status tests, physical and neurological exams, biofluid (CSF and blood) tests and brain imaging.
Before initiating this anti-amyloid treatment, the prescribing information requires that a physician confirms the presence of beta-amyloid plaques. Tools such as an amyloid PET scan or lumbar puncture (CSF tests) are examples of tests that may be required.
Your health care provider will also do a magnetic resonance imaging (MRI) scan before starting treatment with lecanemab. Some people have a genetic risk factor (ApoE ε4 gene carriers) that may cause an increased risk for the side effect of amyloid-related imaging abnormalities (ARIA). The FDA encourages that testing for ApoE ε4 status should be performed prior to initiation of treatment to inform the risk of developing ARIA. Prior to testing, doctors should discuss with patients the risk of ARIA and the implications of genetic testing results.
How do I receive this treatment?
If you or a loved one is experiencing memory changes, the Alzheimer's Association strongly encourages speaking with a health care provider for a thorough evaluation and diagnosis. Individuals should talk with their health care provider to develop a treatment plan that is right for them, including weighing the benefits and risks of all approved therapies.
