New Data at CTAD 2025 Validates LEQEMBI’s Effects on Alzheimer’s

Eisai Co., Ltd. and Biogen Inc. announced significant findings regarding their treatment for Alzheimer’s disease, LEQEMBI (lecanemab-irmb), at the 18th Clinical Trials on Alzheimer’s Disease (CTAD) Conference held in December 2025. New data presented confirms the pharmacological effect of lecanemab on neurotoxic Aβ protofibrils in cerebrospinal fluid (CSF), marking a crucial milestone in understanding its role in slowing the progression of Alzheimer’s disease (AD).

The data stems from a large-scale clinical study that demonstrates, for the first time, measurable binding of lecanemab to Aβ protofibrils in CSF. This finding is particularly relevant as AD is characterized by the accumulation of amyloid beta (Aβ) and tau proteins, both pivotal in the disease’s neurotoxic processes. The study indicated that targeting both protofibrils and amyloid plaques distinguishes LEQEMBI from other treatments, potentially impacting tau pathology downstream.

In a specific sub-cohort of the Phase III Clarity AD study, researchers quantified total Aβ protofibril concentrations in the CSF from 410 participants. The results revealed that the placebo group experienced a 19% increase in total protofibril concentration at the 12-month mark, escalating to 29% by 18 months. Conversely, the lecanemab group exhibited a remarkable 59% increase at 12 months and a 45% increase at 18 months, with the difference from the placebo group being statistically significant (p=0.0126).

The increase in CSF protofibril concentration in patients receiving lecanemab suggests that the drug effectively binds to protofibrils, thereby facilitating their mobilization from the brain to the CSF. Researchers interpret this as a potential mechanism by which lecanemab mitigates the toxic effects of protofibrils, thereby reducing neurodegeneration and cognitive impairment.

A notable finding was the correlation between changes in CSF protofibrils and neurodegeneration biomarkers in the placebo group, which disappeared with lecanemab treatment. This suggests that lecanemab may effectively reduce neurotoxicity by binding to harmful protofibrils, reinforcing its unique position as the only AD treatment targeting both protofibrils and amyloid plaques.

LEQEMBI is indicated for the treatment of Alzheimer’s disease, specifically in patients with mild cognitive impairment or mild dementia. Treatment with LEQEMBI is initiated in these early stages, as confirmed by clinical trials.

Despite the promising data, the treatment comes with warnings regarding amyloid-related imaging abnormalities (ARIA), which can manifest as edema or hemorrhage in the brain. These abnormalities are most commonly observed early in treatment and can lead to serious complications. The incidence of symptomatic ARIA was noted at 3%, with serious ARIA symptoms reported in 0.7% of patients receiving lecanemab.

Patients who are homozygous for the apolipoprotein E ε4 allele, approximately 15% of AD patients, exhibit a higher incidence of ARIA related to treatment with LEQEMBI. Testing for this genetic marker is recommended prior to starting treatment, and physicians are advised to discuss the implications of genetic testing with patients.

The trial results and safety profile of LEQEMBI have positioned Eisai and Biogen as leaders in the fight against Alzheimer’s disease. Eisai is leading the global development and regulatory submissions for lecanemab, while both companies share responsibilities for co-commercialization and promotion.

The implications of this research are profound for the millions affected by Alzheimer’s disease worldwide. By targeting neurotoxic protofibrils, lecanemab may offer new pathways for treatment, potentially altering the course of a disease that has historically been challenging to manage.

As the scientific community continues to explore the complexities of Alzheimer’s disease, the findings from the CTAD conference signify a significant step forward in developing effective treatments and enhancing the quality of life for patients and their families.