On January 6, 2023, the US Food and Drug Administration (FDA) approved lecanemab for the treatment of Alzheimer’s disease (AD), making history as the first ever treatment to significantly slow cognitive decline. The approval follows that of aducanumab last year, and together these drugs represent a new category of medications targeting the Aβ pathology associated with AD.

Lecanemab is unique for its preferential binding of soluble amyloid-β protofibrils compared to aggregated amyloid plaques. In the recently completed Phase III trial, Clarity AD (NCT03887455), lecanemab slowed cognitive decline by 27% compared to placebo, as measured by CDR-SB. Similar slowing of decline was reported in other measures of cognitive function such as ADCOMS, ADAS-Cog14 and ADCS MCI-ADL.

Despite the excitement in the field surrounding this breakthrough approval, concerns remain regarding the extent of lecanemab’s clinical benefit and the risks involved with its use. In this episode, experts delve into the evidence we have to date, reflecting on the performance of lecanemab in clinical trials, how it compares to aducanumab, the risk of hemorrhage, its efficacy in women, and future directions for investigating anti-amyloid immunotherapies.

With Lars Lannfelt, MD, PhD, Uppsala University, Uppsala, Sweden; Alvaro Pascual-Leone, MD, PhD, Hebrew SeniorLife & Harvard Medical School, Boston, MA; and Nicolas Villain, MD, PhD, AP-HP Sorbonne University, Paris, France.