Research Committee

Lecanemab: Slowing Down of Cognitive Impairment Without Reversing It or Improving Cognition

By Mariya Kovaleva

Lecanemab is a monoclonal antibody medication that received accelerated approval from the Food and Drug Administration on January 6, 2023. Lecanemab has been tested in a multi-national 18-month double-blinded 1:1 placebo-controlled randomized trial (N = 1795 participants were enrolled). Lecanemab has been administered biweekly, intravenously, at 10 mg/kg.

Lecanemab cleared amyloid-β peptide – a toxic protein biomarker of Alzheimer’s disease – in a sample of people with mild cognitive impairment and mild dementia due to Alzheimer’s disease. By 18 months, 68% of persons attained total clearance of amyloid-β peptide. Additionally, lecanemab reduced the rate of cognitive and functional impairment. By 18 months, 24% of those taking lecanemab attained a decline of one “global” rating on the Clinical Dementia Rating Scale. By contrast, 32% of individuals on placebo demonstrated the same reduction. Thus, lecanemab slowed dementia progression. Importantly, lecanemab did not stop the progression of dementia, nor did it improve participants’ cognitive or functional status.

Adverse events were frequent: 88.9% of participants in the lecanemab experienced at least one adverse event ranging from anxiety to death (six people died). Fourteen percent of participants experienced serious adverse events. The most common adverse events were amyloid-related imaging abnormalities (ARIAs), including brain edema, effusions, or brain hemorrhage. Specific information was elucidated regarding the apolipoprotein E (APOE) ε4 carrier status. APOE gene encodes the data for a protein that transports cholesterol in the blood. There are three alleles (variants) of the APOE gene – ε2, ε3, and ε4. APOE ε4 confers the highest risk for Alzheimer’s disease. Among the trial participants in the experimental group, 9.2% of individuals who were homozygous for the APOE ε4 incurred ARIAs. This is compared to 1.4% of individuals who did not carry APOE ε4 and developed ARIAs.

Medicare does not currently cover lecanemab, and the cost of taking this medication is very high: $26,500 annually. For the Centers for Medicare and Medicaid to cover the cost of the drug, it must be shown as a proper and necessary treatment. This contrasts with the Food and Drug Administration approval requirement that the drug is safe and effective. High cost, modest benefit, increased risks of adverse effects, and the challenges associated with bi-weekly intravenous injections make it uncertain who will benefit from lecanemab. Total clearance of amyloid-β peptide and clinical benefits for cognition and functional status are encouraging and remarkable findings; however, longer medication trials of this medication are warranted.

Mariya Kovaleva, RN, PhD, MS, AGPCNP-BC