Van Dyck and colleagues report a double blind, multi-center, phase 3 clinical trial investigating a monoclonal antibody, lecanemab, in people with early Alzheimer’s disease (AD). A total of 1795 patients with mild cognitive impairment/mild dementia secondary to AD were recruited and randomised either to lecanemab (10mg/kg every two weeks) or placebo infusions over an 18 month period (898 and 897 patients, respectively). Randomisation was stratified to account for clinical state, medication, and apolipoprotein E carrier status.
The primary endpoint was the change in the score on the clinical dementia rating (CDR) – Sum of Boxes from baseline at 18 months. Secondary endpoints, measured in a subgroup of patients, included change from baseline at 18 months of amyloid burden on PET (measured in centiloids), as well as CSF/plasma biomarkers for amyloid beta (Aβ1–40 and Aβ1-42), phosphorylated tau 181, and neurofilament chain (NFL).
There was a 27% decrease in cognitive decline in the treatment group compared to placebo, as measured by the magnitude of change in CDR-SB score. In the sub study of amyloid burden on PET (698 participants), mean change in amyloid level in the treatment group was -55.48 centiloids vs. +3.64 in the placebo group. There were significant numerical improvements in all CSF and Plasma biomarkers with exception of NFL.
Lecanemab was associated with greater rate of serious adverse events (14% vs 11.3%), and adverse events leading to trial discontinuation (6.9% vs 2.9%). Most commonly, this was due to infusion related reactions (1.2%), or amyloid related imaging abnormalities (0.8%).
Key points:
- In patients with early AD, lecanemab, reduced brain amyloid levels and slowed down cognitive decline by 27% over an 18 month period.
- Treatment with lecanemab was associated with increased adverse effects, including infusion reactions, and amyloid related imaging abnormalities.
- This study investigated the effects of lecanemab over an 18 months, and longer term trials are needed to clarify the efficacy and safety profiles beyond this study period.
References:
van Dyck CH, Swanson CJ, Aisen P, Bateman RJ, Chen C, Gee M, Kanekiyo M, Li D, Reyderman L, Cohen S, Froelich L, Katayama S, Sabbagh M, Vellas B, Watson D, Dhadda S, Irizarry M, Kramer LD, Iwatsubo T. Lecanemab in Early Alzheimer's Disease. N Engl J Med. 2023 Jan 5;388(1):9-21. doi: 10.1056/NEJMoa2212948. Epub 2022 Nov 29. PMID: 36449413.
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