On July 6, 2023, the FDA announced the traditional approval of lecanemab (Leqembi) for treatment of Alzheimer’s disease. The AAN is preparing resources to guide members about this drug.
What is the difference between lecanemab (Leqembi) and aducanumab (Aduhelm)?
While both products target amyloid beta plaque, the most significant difference is highlighted in the New England Journal of Medicine in late 2022, finding that lecanemab was able to moderately slow decline on measures of cognition and function in patients with early AD and MCI relative to placebo at 18 months of treatment. The FDA announced traditional approval for lecanemab on July 6, 2023. Aducanumab is not being considered for traditional approval.
What are the side effects of lecanemab (Leqembi)?
Amyloid-related imaging abnormalities (ARIA) are the most common side effect in clinical trials. ARIA was more common in patients with ApoE4 genotype. There are two types of ARIA, ARIA-E refers to vasogenic edema identified on FLAIR MRI sequences, and ARIA-H microhemorrhages and hemosiderosis. ARIA is monitored through MRIs performed before an infusion unless a patient develops any symptoms in between infusions. While most cases of ARIA in the clinical trials were asymptomatic, a subset developed associated symptoms. Infusion reactions are also a possible side effect of this class of drugs. (This was taken from the monoclonal antibody Q&A.) The AAN is developing an edition of "Emerging issues in neurology" to help our members understand the role lecanemab may play in the AD treatment landscape.
What Alzheimer’s patient population is approved for lecanemab (Leqembi)?
The FDA approved lecanemab for patients in the mild cognitive impairment or mild dementia stages of Alzheimer's Disease with proven amyloid beta pathology.
Is lecanemab (Leqembi) covered by Medicare?
Yes, lecanemab is covered by Medicare as long as the provider participates in a prospective comparative study. Read additional information on this requirement. Lecanemab, and all other monoclonal antibodies for the treatment of Alzheimer's Disease (AD), are subject to this National Coverage Determination (NCD) that was finalized by CMS in April of 2022 in response to the approval of aducanumab and the surrounding controversy.
Is lecanemab (Leqembi) clinically effective?
Yes, according to the New England Journal of Medicine article, "lecanemab reduced markers of amyloid in early Alzheimer’s disease and resulted in moderately less decline on measures of cognition and function than placebo at 18 months but was associated with adverse events." The AAN cited this finding in its letter to CMS requesting that the NCD that currently restricts access to lecanemab be reconsidered, as this has demonstrated direct clinical benefit.
What are the next steps?
The AAN submitted comments to CMS requesting that the NCD restricting coverage of lecanemab to randomized controlled trials be reconsidered. The AAN has met with CMS on numerous occasions to discuss this issue and is working closely with the agency's Coverage and Analysis Group to determine the best path forward to ensure appropriate access to this therapy upon full approval of lecanemab.