Eisai Co., Ltd. and Biogen Inc. have announced new findings regarding lecanemab (LEQEMBI®), an anti-amyloid beta (Aβ) protofibril antibody for the treatment of early Alzheimer’s disease (AD). The data, presented at the Clinical Trials for Alzheimer's Disease Conference (CTAD) in Madrid, Spain, highlight the long-term benefits of lecanemab and its potential impact on disease progression.
Sustained Benefits with Long-Term Lecanemab Treatment
Data from the open-label long-term extension (OLE) study of the Phase 3 Clarity AD trial revealed that continued lecanemab treatment for three years resulted in a significant difference in the mean change from baseline in CDR-SB (Clinical Dementia Rating-Sum of Boxes) compared to a prespecified natural history cohort of AD. Specifically, at 36 months, the difference expanded to -0.95 compared to -0.45 at 18 months, indicating a 30% reduction in the relative risk of progressing to the next disease stage.
Furthermore, a tau PET substudy showed that 59% of patients with no or low tau accumulation in the brain at baseline exhibited improvement or no decline after three years of continuous lecanemab treatment. Additionally, 51% showed improvement from baseline on the CDR-SB scale.
Impact of Early Lecanemab Initiation
Additional Clarity AD data presented at CTAD focused on patients with low levels of amyloid accumulation in the brain at baseline (less than 60 Centiloids). These results indicated that 46% of patients improved or had no decline on the CDR-SB, with 33% showing improvement. Similar trends were observed on the ADAS-Cog14 and ADCS MCI-ADL scales, suggesting that earlier initiation of lecanemab treatment may have a positive impact on disease progression and provide continued benefits over the long term.
Protofibrils and Neurodegeneration
Eisai researchers have developed a new method to accurately quantify protofibrils in cerebrospinal fluid (CSF). Using this method, they found that the amount of protofibrils in AD CSF correlated more strongly with neurodegenerative disease biomarkers (CSF total tau and neurogranin) than with CSF Aβ42, indicating that protofibrils are closely related to synaptic dysfunction. These findings suggest that protofibrils play an important role in neurodegeneration in AD brains.
Real-World Lecanemab Use in the U.S.
An analysis of lecanemab treatment in real-world settings in the U.S., based on payment claims data from the Komodo Research Database, showed that access to lecanemab treatment is expanding. The analysis also highlighted opportunities to improve access in rural areas and educational outreach for underserved populations.
Long-term data from patients who continued to receive lecanemab treatment following the Phase II Study 201 and Phase III Clarity AD study showed that more than half of the patients who continued treatment with lecanemab for more than three years after the core phase remained in their initial stage of disease. A survey of patients (or their caregivers) who received lecanemab treatment for more than five years revealed high satisfaction levels, with patients reporting that lecanemab treatment made them feel more positive about their daily life, social activities, and memory.
AHEAD 3-45 Study Update
The AHEAD 3-45 study, a Phase 3 clinical trial for individuals with preclinical AD, has completed patient enrollment. Screening with blood biomarker tests, specifically plasma Aβ42/40 ratio and p-tau217/tau217 ratio, improved eligibility for amyloid PET testing in subjects without cognitive impairment.
