New Data Presented at the Clinical Trials on Alzheimer's Disease (CTAD) Conference 2025 Confirms Pharmacological Effect of LEQEMBI® (lecanemab-irmb) on Neurotoxic Aβ Protofibrils in CSF

Core Insights - The latest data presented at the 18th Clinical Trials on Alzheimer's Disease Conference confirms the pharmacological effect of lecanemab (LEQEMBI) on Aβ protofibrils in cerebrospinal fluid, marking a significant advancement in understanding how lecanemab slows Alzheimer's disease progression [1][7]. Group 1: Clinical Study Findings - A large-scale clinical study demonstrated that lecanemab binds to Aβ protofibrils, which can now be measured in cerebrospinal fluid, providing insights into its mechanism of action [1][5]. - In a sub-cohort of the Phase III Clarity AD study, total Aβ protofibril concentration in cerebrospinal fluid increased by 59% at 12 months and 45% at 18 months in the lecanemab group, compared to a 19% increase at 12 months and 29% at 18 months in the placebo group [4][6]. - The difference in Aβ protofibril concentration changes between the lecanemab and placebo groups was statistically significant at 12 months (p=0.0126) [4]. Group 2: Mechanism of Action - Lecanemab's treatment effect suggests it facilitates the mobilization of Aβ protofibrils from the brain parenchyma into cerebrospinal fluid, thereby mitigating the toxic effects associated with these protofibrils [5]. - The correlation between changes in cerebrospinal fluid Aβ protofibrils and neurodegeneration biomarkers was significant in the placebo group but disappeared with lecanemab treatment, indicating a reduction in neurotoxicity [6]. Group 3: Treatment Indication and Approval - Lecanemab is indicated for the treatment of Alzheimer's disease, specifically for patients with mild cognitive impairment or mild dementia, which aligns with the population studied in clinical trials [9]. - The drug has received approval in 51 countries and regions, including Japan and the United States, and is under regulatory review in 9 additional countries [31]. Group 4: Collaboration and Development - Eisai and Biogen have been collaborating on the development and commercialization of Alzheimer's disease treatments since 2014, with Eisai leading the regulatory submissions globally [35]. - The strategic research alliance between Eisai and BioArctic has been pivotal in the development of lecanemab, with Eisai holding global rights for its study, development, and marketing [36].