Drug Development

Lecanemab is the only monoclonal antibody currently available that targets soluble amyloid-beta (Aβ) protofibrils. It was introduced in China in 2024, but its real-world efficacy remains to be demonstrated. This study aims to evaluate the efficacy and safety of Lecanemab in real-world practice in South China.

This was an 18-month, multicenter, single-arm, open-label, prospective observational study conducted across 25 centers. We plan to recruit 500 patients aged 50 to 90 years with mild to moderate AD within 1 year. Participants were treated with Lecanemab (10 mg/kg) biweekly. Evaluations included neuropsychological assessments, plasma biomarkers (Aβ42, Aβ40, GFAP, t-Tau, p-Tau217, p-Tau181, GFAP using Simoa), and other laboratory tests. Amyloid-Related Imaging Abnormalities (ARIA) were assessed using magnetic resonance imaging (MRI).

A total of 160 participants were recruited (58.75% female, 41.25% male) as of January, 2025, with a mean age of 68.8 ± 9.1 years. Baseline Mini-Mental State Examination (MMSE) score was 17.3 ± 6.5, Clinical Dementia Rating-Sum of Boxes (CDR-SB) score was 5.8 ± 3.6. Regarding APOE ε4 status, 55.63% were carriers, including 18 homozygotes (11.25%). As of now, 21 participants have completed two blood biomarker tests. The baseline levels of blood biomarkers included Aβ42(3.54 ± 2.30 mmol/L), Aβ40( 88.93 ± 39.67 mmol/L), Aβ42/40(0.039 ± 0.014), GFAP(234.84 ± 161.76 mmol/L), and p-Tau217( 0.99 ± 0.55mmol/L). At 14 weeks, biomarkers showed some improvement: Aβ42(5.71 ± 2.68 mmol/L), Aβ40(144.08 ± 46.86 mmol/L), Aβ42/40(0.037 ± 0.009), GFAP(215.38 ± 144.42mmol/L) and p-Tau217( 0.92 ± 0.41 mmol/L). The most common adverse events were infusion-related reactions (22.5%), and ARIA occurred in 15 cases (10.0%), with only 6 cases being symptomatic.

Lecanemab was generally well-tolerated and the improvements in blood biomarkers suggest that it may have a beneficial impact on disease progression.