Consistent benefits with lecanemab seen in Clarity AD Asian cohort

In the treatment of early Alzheimer’s disease (AD), lecanemab is as safe and efficacious in Asian patients as in the wider Clarity AD population, slowing cognitive decline and reducing amyloid levels in the brain with manageable risks.

Subgroup analysis including patients enrolled from Japan, Korea, and Singapore showed that lecanemab was associated with a 24-percent reduction in the primary endpoint of clinical decline on the global cognitive and functional scale (Clinical Dementia Rating–Sum of Boxes [CDR-SB]) at 18 months compared with placebo (adjusted mean difference, –0.349, 95 percent confidence interval [CI], –0.773 to 0.076). [J Prev Alzheimers Dis 2025:doi:10.1016/j.tjpad.2025.100160]

Results for the secondary efficacy endpoints also favoured lecanemab vs placebo in Asians. At 18 months, there was a 25-percent reduction in cognitive decline as measured by the AD Assessment Scale–cognitive subscale14 (difference, −1.37, 95 percent CI, −2.89 to 0.14), a 24-percent decrease in the AD Composite Score (difference, −0.05, 95 percent CI, −0.10 to −0.00), and a 23-percent reduction in functional decline as measured by the AD Cooperative Study–Activities of Daily Living Scale for Mild Cognitive Impairment (difference, 1.31, 95 percent CI, −0.47 to 3.09).

Furthermore, a greater decrease in amyloid levels in the brain measured by amyloid PET (−72.2, 95 percent CI, −84.1 to −60.4) and positive effects on plasma biomarkers of amyloid (Aβ42/40 ratio, −0.87, 95 percent CI, −1.09 to −0.64), tau (pTau181, 0.010, 95 percent CI, 0.008–0.011), and neuroinflammation (glial fibrillary acidic protein, −97.17, 95 percent CI, −118.99 to −75.35; neurofilament light chain, −1.92, 95 percent CI, −4.38 to 0.53) were observed with lecanemab vs placebo.

Health-related quality of life (QOL) was relatively preserved in Asian patients receiving lecanemab, while caregiver burden increased less, with consistent favourable effects observed across different QOL scales.

Safety

Treatment was well tolerated, with most adverse events (AEs) being mild to moderate. The most common AEs of special interest were amyloid-related imaging abnormalities (ARIA) hemosiderin deposits (ARIA-H) (14.4 percent with lecanemab vs 16.2 percent with placebo), ARIA edema (ARIA-E) (6.2 percent vs 1.4 percent, respectively), and infusion-related reactions (12.3 percent vs 1.4 percent, respectively).

Notably, AEs leading to study drug dose interruption or withdrawal, infusion-related reactions, ARIA-E, and ARIA-H occurred less frequently with lecanemab in the Asian cohort relative to the overall Clarity AD population.

“The mechanism for the lower frequency of AEs in the Asia region is not clear, especially given the ApoE4 carrier frequency in the Asia region (72.6 percent) was similar to that in the overall population (69.0 percent),” the investigators said.

A lower cerebral amyloid angiopathy prevalence in Asia and differences in amyloid burden may potentially explain the lower AE rates, although research around them is limited and inconclusive, they added.

“In summary, in this Asia region cohort, the overall efficacy, biomarker changes, and safety profile of lecanemab were consistent with the overall population, with a favourable risk-benefit profile,” the investigators said.

The analysis included 294 patients with early AD, of which 146 were in the lecanemab arm (mean age 70.3 years, 58.2 percent female) and 148 in the placebo arm (mean age 69.8 years, 58.1 percent female). Baseline demographic and disease-related characteristics in the Asian population were generally similar to those of the overall population, except for the lower mean body weight and slightly higher rates of mild cognitive impairment due to AD and global Clinical Dementia Rating score of 0.5 in the Asian population.