Drug Development

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with a significant impact on patients and healthcare systems. Lecanemab, a monoclonal antibody targeting amyloid beta, has recently been approved for early-stage AD, offering potential for disease modification. This report examines the demographic characteristics, treatment responses, and safety profile of early-stage AD patients treated with Lecanemab at the Tel Aviv Medical Center (TLVMC), focusing on 6-month follow-up outcomes.

Since November 2023, Lecanemab has been administered to early-stage AD patients at TLVMC. Data collected included baseline demographics, ApoE4 status, CSF biomarkers (t-tau, p-tau181, Aβ42), plasma p-tau181 levels, and Mini-Mental State Examination (MMSE) scores. Patients were monitored for amyloid-related imaging abnormalities (ARIA), and cognitive outcomes were assessed at 6 months. This report summarizes data for patients who completed the 6-month follow-up by January 2025.

By January 2025, 45 out of 85 patients had completed the 6-month visit. The mean age was 73 years (SD = 7.2), with 53% women and 51% ApoEε4 carriers. Mean baseline CSF biomarker levels (pg/ml): t-tau = 580 (SD = 268), p-tau181 = 194 (SD = 461), and Aβ42 = 333 (SD = 166). Plasma p-tau181 levels (n=27) had a mean value of 32.3 pg/ml (SD = 10.5). The mean baseline MMSE score was 24.02 (SD = 2.59). Plasma p-tau181 levels were significantly correlated with baseline MMSE scores (r = -0.429, p = 0.023). At 6 months, the mean MMSE score decreased to 22.48 (SD = 3.92), a significant decline of 1.47 points from baseline (p = 0.009). Younger patients (<75 years) showed a statistically significant decline in MMSE score (p = 0.007), while older patients (≥75 years) did not. Seven patients (15.5%) developed asymptomatic ARIA-H during the first 6 months.

This 6-month follow-up highlights Lecanemab's potential to preserve cognitive function in early-stage AD, with a lower incidence of ARIA than reported in trials. These findings emphasize the importance of real-world evidence in shaping clinical practice for disease-modifying therapies.