In January, the FDA approved lecanemab (brand name Leqembi™) under the Accelerated Approval Pathway for the treatment of Alzheimer’s disease (AD). On March 27, Appropriate Use Recommendations (AURs) for the drug were published in the Journal of Prevention of Alzheimer’s Disease (JPAD). AURs are intended to help guide the introduction of new therapies into real-world clinical practice.
The lecanemab AURs were co-authored by Stephen Salloway, MD, MS, founder of the Memory and Aging Program at Butler Hospital. In fact, Butler Hospital was among the research sites that carried out studies of lecanemab. Dr. Salloway is also “Martin M. Zucker Professor of Psychiatry and Human Behavior Professor of Neurology” at Alpert Medical School of Brown University and Associate Director of the Brown Center for Alzheimer’s Disease Research.
In a phase 2 trial, lecanemab was observed to produce a marked lowering of amyloid plaques based on evidence derived from amyloid PET. Lecanemab has completed a confirmatory phase 3 trial (CLARITY-AD), and the FDA will review data from that trial to determine if standard approval based on the clinical outcomes of the trial is warranted. A decision is expected sometime in 2023.
Overview of Lecanemab (Leqembi™) Appropriate Use Recommendations
Lecanemab is given intravenously every other week. The AURs for lecanemab adhere closely to the inclusion and exclusion criteria of the drug’s phase 2 and 3 trials. They state that lecanemab may be an appropriate treatment for patients who:
- Have a diagnosis of mild cognitive impairment (MCI) or mild Alzheimer's disease (AD).
- Have evidence of amyloid pathology (the “plaques” in the brain associated with the development of Alzheimer’s disease) as confirmed by PET imaging or cerebrospinal fluid (CSF) testing.
- Are between the ages of 50 and 90.
The AURs recommend that, in most cases, clinicians should avoid prescribing lecanemab to patients who:
- Are younger than 50 or older than 90 years old.
- Have immunologic disorders that were not adequately controlled or require therapy with immunoglobulins, systemic monoclonal antibodies, systemic immunosuppressants, or plasmapheresis.
- Have or have had other unstable medical conditions, stroke, transient ischemic attacks, or bleeding disorders in the previous 12 months.
- Are taking blood thinners such as warfarin.
- Have a history of seizures.
- Have depression that scored greater than 8 on the Geriatric Depression Scale or had a body mass index (BMI) greater than 35 or less than 17.
The AURs also outline screening and monitoring guidelines to reduce the risk of adverse events that may rarely occur with lecanemab including amyloid-related imaging abnormalities (ARIA) and infusion reactions. In addition, it is recommended that all patients be tested for APOE genotyping prior to starting treatment because APOE4 gene carriers are at higher risk for the occurrence of ARIA.
The full Appropriate Use Recommendations for lecanemab may be viewed here.
Study of Lecanemab in Preventing Cognitive Decline Now Enrolling
The Memory and Aging Program at Butler Hospital is currently enrolling cognitively normal participants for another study of lecanemab called the AHEAD Study. This study is evaluating how effective lecanemab is at maintaining normal cognitive abilities and reducing levels of amyloid and tau plaques in the brain.
To learn more information about the AHEAD study while also learning more about Alzheimer’s disease risk, click here.
Disclaimer: The content in this blog is for informational and educational purposes only and should not serve as medical advice, consultation, or diagnosis. If you have a medical concern, please consult your healthcare provider, or seek immediate medical treatment.