Is there anything you can do to slow down the cognitive decline?” Each of us fields this question almost immediately after making a diagnosis of Alzheimer's disease (AD). For many years, we have had to answer by gesturing toward future possibilities. This answer may soon change, thanks to results from Clarity AD, a phase 3 randomized clinical trials of lecanemab for patients with
early AD.1 While lecanemab was recently granted accelerated approval by the US Food and Drug Administration (FDA) based on earlier phase 2 data demonstrating significant amyloid plaque reduction by positron emission tomography (PET), consideration for full approval will follow later this year based on the clinical efficacy demonstrated by the phase 3 study, confirming the clinical signal observed in the phase 2 study.

Lecanemab is a humanized IgG1 monoclonal antibody that binds to amyloid-β (Aβ) soluble protofibrils.
In Clarity AD, 1795 patients with mild cognitive impairment (MCI) or mild dementia due to AD were randomly assigned to receive 10-mg/kg biweekly intravenous infusions of lecanemab or placebo for 18 months. Primary and secondary outcomes, as well as multiple “downstream” biomarkers of AD pathophysiology, all favored lecanemab, demonstrating a clear-cut clinical benefit and possible modification of disease pathophysiology. The Clarity AD results converge with the phase 2 donanemab data (TRAILBLAZER-ALZ)2 and 1 of 2 phase 3 aducanumab trials (EMERGE). Conversely, the ENGAGE trial (aducanumab) and phase 3 gantenerumab studies did not demonstrate clinical benefit. These discrepancies may be explained by differences within this antibody class, with donanemab and lecanemab appearing to be more potent in amyloid plaque reduction. In aggregate, these drugs robustly lowered amyloid plaques and resulted in modest slowing
(22%-27%) of clinical decline.

Read PDF: a_step_forward_in_the_fight_against_dementia.pdf