Eisai Co announced that the latest findings demonstrating the benefits of continuous treatment with lecanemab-irmb (U.S. brand name: LEQEMBI), an anti-amyloid beta (AB) protofibril* antibody for the treatment of early Alzheimer’s disease (AD), were presented at the Alzheimer’s Association International Conference (AAIC) 2025, held in Toronto, Canada, and virtually. Only lecanemab fights AD in two ways – targeting both amyloid plaque and protofibrils*, which can impact tau downstream.
Four years of Lecanemab Therapy helped patients slow the progression of AD and remain in the early stages of AD longer compared to AD’s natural course
Clarity AD is a global Phase 3 placebo-controlled, double-blind, parallel-group, randomised study to evaluate lecanemab 10 mg/kg bi-weekly IV treatment of early Alzheimer’s disease, which involved 1,795 patients(treatment group: 898, placebo group: 897). 95 per cent of patients who completed the core study (18 months) chose to continue in the open-label extension study (OLE), with 478 patients still receiving treatment for four years. In the Clarity AD core study, the mean change from baseline between the lecanemab-treated group and the placebo group after 18 months was -0.45 (P=0.00005) on the primary endpoint of CDR-SB global cognitive and functional scale.
To provide context, a change from 0.5 to 1 on the Clinical Dementia Rating (CDR) score domains of Memory, Community Affairs and Home/Hobbies reflects a shift from mild impairment to loss of independence. This can affect a person’s ability to be left alone safely, recall recent events, participate in daily activities, manage household tasks, and engage in hobbies and intellectual interests.
Over three years of treatment, including both the core study and the OLE, data showed that lecanemab demonstrated a reduction in cognitive decline—measured by CDR-SB—of 1.01 points compared to the expected decline observed in the Alzheimer’s Disease Neuroimaging Initiative (ADNI)** cohort. This benefit grew more pronounced after four years, with a reduction of 1.75 points. Similarly, when benchmarked against the expected decline in the BioFINDER*** cohort, lecanemab showed a reduction of 1.40 points at three years and an even greater reduction of 2.17 points at the four-year mark.
Consistent safety profile observed over four years of Lecanemab treatment
No new safety findings were observed in the OLE with continued lecanemab treatment over four years. Rates of amyloid-related imaging abnormalities (ARIA) decreased after the initial 12 months and remained consistent throughout four years of continuous treatment. As stated in the FDA product label, the incidence and timing of ARIA vary among treatments.
More than 50 per cent of patients who started treatment in the earlier stages of AD continued to show improvement in clinical scores after four years of Lecanemab Therapy
The Clarity AD study included an optional tau PET substudy and used the MK6240 tracer to identify patients with low levels of tau accumulation in the brain, an indicator of early-stage AD Among these patients, after four years of lecanemab treatment, 69 per cent of these patients showed improvement or no decline, and 56 per cent showed improvement from baseline on the CDR-SB. The benefit observed at 18 months was sustained through four years of treatment. On the ADAS-Cog14 scale, 51 per cent of patients showed improvement or no decline, and 51 per cent showed improvement. On the ADCS MCI-ADL scale, 64 per cent of patients showed improvement or no decline, and 58 per cent showed improvement. These findings suggest that initiating and maintaining treatment with lecanemab in early-stage AD may help slow clinical decline and may provide sustained benefits over the long term.
* Protofibrils are thought to be the most toxic Aβ species that contribute to brain damage in AD and play a major role in the cognitive decline of this progressive and devastating disease. Protofibrils can cause neuronal and synaptic damage in the brain, which can subsequently adversely affect cognitive function through multiple mechanisms. The mechanism by which this occurs has been reported not only by increasing the formation of insoluble Aβ plaques, but also by directly damaging signalling between neurons and other cells. It is believed that reducing protofibrils may reduce neuronal damage and cognitive impairment, potentially preventing the progression of AD.
**ADNI is a clinical research project launched in 2005 to develop methods to predict the onset and progression of AD and to confirm the effectiveness of treatments. The project involves a multi-year longitudinal observation targeting healthy elderly individuals as well as patients with mild cognitive impairment (MCI) and early stages of AD.
*** BioFINDER subjects are similar to Study 301 and ADNI subjects, except all BioFINDER subjects are in the MCI stage, and no mild AD subjects are included, and their baseline CDR-SB is lower. BioFINDER is a large-scale, long-term prospective study led by Lund University in Sweden, aiming to establish early diagnosis and elucidate pathophysiology of neurodegenerative diseases. In addition to AD, the study also focuses on conditions including Parkinson’s Disease. Individuals participating in the study undergo regular clinical assessments, cognitive function tests, brain imaging (MRI, Aβ PET, Tau PET), and collection of biomarkers from blood and cerebrospinal fluid (CSF).