Eisai and Biogen presented new data at the Clinical Trials for Alzheimer's Disease Conference (CTAD) in Madrid, Spain, highlighting the long-term benefits of lecanemab (LEQEMBI) in patients with early Alzheimer's disease (AD). The data included findings from an open-label long-term extension study (OLE) and insights from real-world clinical use in the United States.
Sustained Benefits with Long-Term Lecanemab Treatment
Results from the OLE study, following the Phase 3 Clarity AD trial, demonstrated that the mean change from baseline in CDR-SB (Clinical Dementia Rating-Sum of Boxes) in the lecanemab-treated group, relative to a prespecified natural history cohort of AD, was -0.45 at 18 months and -0.95 at 36 months. This suggests a 30% reduction in the relative risk of progressing to the next disease stage with continued treatment.
Furthermore, a tau PET substudy of the Clarity AD trial indicated that after three years of continuous lecanemab treatment, 59% of patients with no or low tau accumulation in the brain at baseline showed improvement or no decline, and 51% showed improvement from baseline on the CDR-SB scale.
Clarity AD data presented at CTAD expand on these initial results to include additional measurements resulting from three (3) years of continuous lecanemab treatment in patients with low levels of amyloid accumulation in the brain at baseline (less than 60 Centiloids: low amyloid). These data show that 46% of patients improved or had no decline, and 33% showed improvement from baseline on the CDR-SB. On the ADAS-Cog14 measurement scale, 46% of patients showed improvement or no decline and 43% showed improvement. On the ADCS MCI-ADL, 51% of patients showed improvement or no decline and 48% showed improvement. These results – from no tau/low tau population and low amyloid populations – suggest that earlier initiation of lecanemab treatment may have a positive impact on disease progression of early AD patients and may provide continued benefits to patients with early AD over the long term.
Notably, no new safety findings were observed with continued lecanemab treatment over three years. Most amyloid-related imaging abnormalities (ARIA) occurred within the first six months of treatment, with rates decreasing thereafter, regardless of ApoEε4 status.
Protofibrils and Neurodegeneration
Eisai researchers have developed a new method to accurately quantify protofibrils in cerebrospinal fluid (CSF). Using this method, they found a stronger correlation between protofibrils and neurodegenerative disease biomarkers (CSF total tau and neurogranin) than with CSF Aβ42, a biomarker associated with Aβ plaque accumulation. This suggests that protofibrils play a significant role in synaptic dysfunction and neurodegeneration in AD brains.
Real-World Lecanemab Use in the U.S.
An analysis of lecanemab treatment between January 6, 2023, and July 30, 2024, using data from the Komodo Research Database, indicated that access to lecanemab is expanding in the U.S. However, the analysis also highlighted opportunities to improve access in rural areas and increase educational outreach for underserved populations.
Data from the Alzheimer's Research and Treatment Center showed that of 136 patients participating in both the Phase II Study 201 and Phase III Clarity AD study, 66 chose to continue lecanemab therapy, with 13 receiving treatment for over five years and 40 for over three years. More than half of the patients (15/24) who continued treatment with lecanemab for more than three (3) years after the core phase remained in their initial stage of disease. Furthermore, a survey of 11 patients (or their caregivers) who received lecanemab treatment for more than five years revealed high satisfaction levels and positive impacts on daily life, social activities, and memory.
AHEAD 3-45 Study Updates
The AHEAD 3-45 study, a Phase 3 clinical trial for individuals with preclinical AD, completed enrollment in October 2024. The study utilizes blood tests, cognitive function tests, amyloid PET, MRI, and tau PET for screening. The use of plasma Aβ42/40 ratio and p-tau217/tau217 ratio in the initial screening reduced screening failure on amyloid PET from over 70% to less than 30%, demonstrating the utility of blood biomarkers in identifying elevated amyloid in the brain.
CTAD Lifetime Achievement Award
Professor Emeritus Lars Lannfelt of Uppsala University received the CTAD Lifetime Achievement Award for his contributions to scientific discovery and drug development in AD, including his work on the arctic mutation in familial AD and the development of lecanemab.
