Disease-modifying effects of lecanemab in AD maintained through 24 months

medwireNews: Lecanemab continues to show a disease-modifying effect through 24 months in patients with early Alzheimer’s disease (AD), show initial findings from the open-label phase of the CLARITY AD study, with particular benefit suggested for those at an early pathogenetic stage. Christopher van Dyck (Yale School of Medicine, New Haven, Connecticut, USA) discussed the findings at AD/PD 2024 in Lisbon, Portugal, saying that the “delayed start and lower pathology group results support early initiation of treatment with lecanemab.” The core CLARITY AD trial involved 1795 patients with early Alzheimer’s disease (AD) who were randomly assigned to receive lecanemab 10 mg/kg or placebo every 2 weeks for 18 months. At this point, there was significantly less decline in the active treatment group versus placebo group on the Clinical Dementia Rating Scale (CDR)-SB, with a mean difference of 27% in favor of lecanemab, as well as on the AD Assessment Scale–Cognitive subscale (ADAS-cog14; mean difference 26%) and the AD Cooperative Study–Activities of Daily Living for Mild Cognitive Impairment (ADCS MCI-ADL; mean difference 37%). The participants then entered an open-label phase for a further 6 months, during which all participants received lecanemab. Between 18 and 24 months, the disease trajectories were still parallel and the significant difference between lecanemab- and placebo-treated patients on the CDR-SB, ADAS-cog14, and ADCS MCI-ADL remained, so the late-starters did not catch up, said van Dyck, which “suggests disease modification.” To determine whether patients starting lecanemab at 18 months still benefitted from treatment, the researchers used a historical control group (Alzheimer’s Disease Neuroimaging Initiative) matched to the CLARITY AD population for baseline demographics and clinical characteristics. The disease trajectory of these individuals was similar to that of the CLARITY AD placebo group out to 18 months but then showed “an acceleration of decline” between 18 and 24 months, whereas switching to lecanemab was associated with more disease stability, said van Dyck. Van Dyck also discussed the potential outcomes for patients with particularly early disease, based on exploratory findings from the tau positron emission tomography (PET) substudy (n=342), which showed similar efficacy results to the overall study population at 18 months (significant 37.9% less decline on CDR-SB), a slowing of tau spread with lecanemab versus placebo, particularly in the temporal lobe regions, and consistent lowering of amyloid in the 141 patients with low ( 2.91 SUVr) tau levels over the course of the study. At 18 months, an estimated 93.3% of patients with low tau PET had amyloid PET clearance (<30 centiloids), compared with 56.9% of patients with intermediate-to-high tau PET and 71.8% for the whole tau PET subpopulation. This suggests that “individuals with low tau – and thus at an earlier pathogenetic stage – show clinical stability or improvement,” said van Dyck, adding that the findings “raise the question of whether patients at the early pathogenetic stage may benefit more.” Due to the relatively small tau PET substudy sample size, van Dyck and team estimated a similar stage of disease based on an amyloid PET level below 60 centiloids for the whole CLARITY AD population. Exploratory analyses suggested that for these patients, there was even less decline on the CDR-SB, ADAS-cog14, and ADCS MCI-ADL at 18 months, at 51%, 69%, and 72%, and as for the whole population, these patients continued to benefit from lecanemab through 24 months. medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2024 Springer Healthcare Ltd, part of the Springer Nature Group This article was originally published on Journey to a New Era for Alzheimer’s Disease, an independent education program developed by Springer Healthcare IME. This program is supported by an educational grant from Lilly. This content is intended for healthcare professionals outside of the UK. AD/PD 2024; Lisbon, Portugal: March 5–9

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Disease-modifying effects of lecanemab in AD maintained through 24 months

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