Lecanemab Slows Alzheimer's Decline in First Large Chinese Real-World Study
261 Chinese AD patients showed slowed cognitive decline and robust amyloid clearance with lecanemab, with plasma p-tau217 emerging as a key response marker.
Summary
A prospective multicenter study across 21 Chinese sites evaluated lecanemab in 261 Alzheimer's disease patients over 6 months. Compared to a matched ADNI cohort, lecanemab significantly attenuated cognitive decline across MCI to moderate dementia stages. Plasma biomarkers including Aβ42, Aβ40, p-tau217, and GFAP showed robust improvements. Amyloid PET revealed a mean reduction of 22.1 Centiloids, with 29.2% of patients turning amyloid-negative. APOE ε4 non-carriers showed greater cognitive benefits. Safety was acceptable, with infusion reactions in 11.1% and ARIA in 9.2% (only 1.6% symptomatic), and no increased risk in moderate dementia patients. Plasma p-tau217 emerged as a promising minimally invasive treatment-response biomarker.
Detailed Summary
Lecanemab, an anti-amyloid beta protofibril antibody approved in China in 2024, had not yet been evaluated in large-scale real-world settings among Chinese patients. This study fills that critical gap by reporting the first multicenter, prospective real-world data from a Chinese Alzheimer's disease population.
Researchers enrolled 261 patients spanning mild cognitive impairment (MCI) to moderate dementia across 21 clinical sites, all receiving biweekly intravenous lecanemab at 10 mg/kg for 6 months. A carefully matched cohort from the Alzheimer's Disease Neuroimaging Initiative (ADNI) served as a comparator group. Outcomes included standard cognitive assessments, a panel of plasma biomarkers, and optional amyloid and tau PET imaging.
Lecanemab significantly slowed cognitive decline relative to the ADNI comparator cohort across disease stages. On the plasma biomarker front, Aβ42, Aβ40, phosphorylated tau 217 (p-tau217), glial fibrillary acidic protein (GFAP), and their ratios all showed meaningful changes consistent with target engagement. Critically, reductions in plasma p-tau217 correlated strongly with amyloid PET clearance, with a mean reduction of 22.1 Centiloids observed and 29.2% of patients converting from amyloid-positive to amyloid-negative status — suggesting plasma p-tau217 could serve as a non-invasive, cost-effective surrogate for PET-based treatment monitoring.
Genetic background mattered: APOE ε4 non-carriers demonstrated greater cognitive improvements than carriers, echoing patterns seen in the pivotal CLARITY AD trial. Importantly, the drug was well tolerated across all AD stages. Infusion-related reactions occurred in 11.1% of patients, and amyloid-related imaging abnormalities (ARIA) were detected in 9.2%, but only 1.6% were symptomatic — rates comparable to or lower than those reported in clinical trials. No stage-dependent increase in adverse events was observed, suggesting moderate dementia patients can be treated without additional safety concerns.
These findings carry significant implications for the rapidly growing Chinese AD patient population and for global generalizability of lecanemab's efficacy. The validation of plasma p-tau217 as a treatment-response biomarker is particularly actionable, potentially reducing the need for expensive or invasive PET scans in monitoring therapy. However, the 6-month observation window and lack of a randomized control group are meaningful constraints on interpretation.
Key Findings
- Lecanemab significantly attenuated cognitive decline vs. matched ADNI controls across MCI to moderate dementia stages.
- Amyloid PET showed mean −22.1 Centiloid reduction; 29.2% of patients converted to amyloid-negative status.
- Plasma p-tau217 reduction strongly correlated with amyloid PET clearance, validating it as a treatment-response biomarker.
- APOE ε4 non-carriers showed greater cognitive improvements than carriers.
- ARIA occurred in 9.2% (1.6% symptomatic) with no increased safety risk in moderate dementia patients.
Methodology
Prospective, multicenter, open-label real-world study across 21 Chinese sites enrolling 261 AD patients (MCI to moderate dementia) receiving biweekly lecanemab 10 mg/kg for 6 months. A propensity-matched ADNI cohort served as comparator. Outcomes included cognitive scales, plasma biomarkers (Aβ42, Aβ40, p-tau217, GFAP), and optional amyloid/tau PET imaging.
Study Limitations
The 6-month follow-up is relatively short for a slowly progressive disease, limiting conclusions about long-term efficacy and safety. The absence of a randomized placebo control — replaced by an external ADNI comparator — introduces potential confounding from population differences. Moderate dementia patients are outside the current approved indication in some markets, and optional PET imaging meant not all patients had imaging biomarker data.
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