Leqembi and Down Syndrome
The NTG has accumulated a selective library of publications and news regarding Leqembi (lecanemab) and Down syndrome.
On January 6, 2023 the U.S. Food & Drug Administration (FDA) granted accelerated approval for lecanemab, an anti-amyloid drug designed to treat Alzheimer’s disease that was developed by the pharmaceutical firms Eisai and Biogen. Lecanemab, branded as Leqembi, is approved to treat adults in the mild stage of Alzheimer’s dementia who also have “confirmed presence of amyloid beta pathology” in the brain. The presence of these amyloid beta plaques in the brain is one of the hallmarks of Alzheimer’s disease.
A Step Forward in the Fight Against Dementia -- Are We There Yet?
This viewpoint reports on the results of the Clarity AD trial, a phase 3 randomized clinical trial of lecanemab for patients with early Alzheimer disease, in which lecanemab’s clinical efficacy was demonstrated using well-established outcome measures. Authors discuss the implications of the findings and the reported risks. From a clinician's perspective, they comment that persons diagnosed with Alzheimer's disease should have access to this drug, although no mention is made of its safety or applicability to adults with intellectual disability. The authors note the work that still remains to be undertaken, lecanemab's success represents a major milestone for the field, and what they consider as a moment of great hope for patients and families living with Alzheimer's disease.
Source: Wolk DA, Rabinovici GD, Dickerson BC. A Step Forward in the Fight Against Dementia-Are We There Yet? JAMA Neurol. 2023 Mar 13. doi: 10.1001/jamaneurol.2023.0123. Epub ahead of print. PMID: 36912845.
F.D.A. Approves Lecanemab as New Treatment for Early Alzheimer’s
Food and Drug Administration on January 7, 2023, approved another Alzheimer’s drug that may modestly slow the pace of cognitive decline early in the disease, but also carries risks of swelling and bleeding in the brain.
Lecanemab For Treating Alzheimer’s Disease: New Clinical Trial Results from Patients with Early-Stage Disease
LuMind IDSC has noted that there remain substantial barriers to Leqembi being deemed safe and accessible for people with Down syndrome, as no one with Down syndrome was included in the Leqembi clinical trials to date. LuMind IDSC recommends that a safety study specifically geared to people with Down syndrome should take place prior to widespread use in the Down community.
Lecanemab: Appropriate Use Recommendations
Lecanemab (Leqembi®) is a therapeutic approved in the United States for the treatment of Alzheimer’s disease (AD) to be initiated in early AD (mild cognitive impairment [MCI] due to AD or mild AD dementia) with confirmed brain amyloid pathology. Appropriate Use Recommendations (AURs) are intended to help guide the introduction of new therapies into real-world clinical practice. Adverse events may occur with lecanemab including amyloid related imaging abnormalities (ARIA) and infusion reactions. Monitoring guidelines for these events are detailed in this AUR. Most ARIA with lecanemab is asymptomatic, but a few cases are serious or, very rarely, fatal. Microhemorrhages and rare macrohemorrhages may occur in patients receiving lecanemab. Anticoagulation increases the risk of hemorrhage, and the AUR recommends that patients requiring anticoagulants not receive lecanemab until more data regarding this interaction are available. Patients who are apolipoprotein E ε4 (APOE4) gene carriers, especially APOE4 homozygotes, are at higher risk for ARIA, and the AUR recommends APOE genotyping to better inform risk discussions with patients who are lecanemab candidates. Patients and their care partners must understand the potential benefits, the potential harms, and the monitoring requirements for treatment with this agent.
“Persons with Down syndrome develop AOAD and are amyloid positive. There is an increased occurrence of CAA in patients with Down syndrome and they should be excluded from treatment with lecanemab. Clinical trials for patients with Down syndrome are under consideration and additional data including information that may guide the use of lecanemab in this population are expected.” [p. 13]
Source: Cummings, J., Apostolova, L., Rabinovici, G.D. et al. Lecanemab: Appropriate Use Recommendations. J Prev Alzheimers Dis (2023). https://doi.org/10.14283/jpad.2023.30
Legembi - FDA Prescriptive Information
Drug label information
The F.D.A. included narrower and more cautionary language on the drug label than it initially had with Aduhelm. The Leqembi label says the drug should be used only for patients in early and mild stages of Alzheimer’s disease, matching the status of patients in the clinical trials of the drug. It instructs doctors not to treat patients without doing tests to confirm that they have one of the hallmarks of Alzheimer’s: a buildup of the protein amyloid, which Leqembi is designed to reduce.