In a study of 88 Japanese participants, donanemab demonstrated a 38.8% slowing of Alzheimer's disease progression compared to placebo at week 76.
The least-squares mean change in score was 4.43 points lower with donanemab than with placebo.
In the low-medium tau subpopulation, donanemab showed a 40.2% reduction in disease progression.
Significant reductions in amyloid plaque and plasma phosphorylated tau 217 were observed in participants receiving donanemab.
was achieved in 83.3% of those treated with donanemab, while no participants in the placebo group experienced this clearance.
Amyloid-related imaging abnormalities occurred in 22.2% of donanemab-treated participants, with only one case being symptomatic.
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INTRODUCTION: Donanemab, a monoclonal antibody directed against an insoluble, modified, N-terminal truncated form of amyloid beta, demonstrated efficacy and safety in patients with early, symptomatic Alzheimer's disease (AD) in the phase 3 TRAILBLAZER-ALZ 2 trial. Here, we report clinical outcomes, biomarkers, and safety results for the Japanese subpopulation.
METHODS: TRAILBLAZER-ALZ 2 (N = 1736) was conducted in eight countries, including Japan (enrollment June 2020-November 2021; database lock April 2023). Participants (60-85 years) with early, symptomatic AD (mild cognitive impairment/mild dementia), Mini-Mental State Examination score 20-28, and confirmed amyloid and tau pathology were randomized 1:1 (stratified by tau status) to intravenous donanemab (700 mg for three doses, then 1400 mg/dose) or placebo every 4 weeks for 72 weeks. Primary outcome was change from baseline to week 76 in (iADRS) score. Other outcomes included clinical measures of cognitive and functional impairment, biomarkers, and safety.
RESULTS: Of 88 Japanese participants (43 placebo, 45 donanemab), 7 in each group discontinued. Least-squares mean (LSM) change from baseline in iADRS score at week 76 was smaller with donanemab than with placebo in the combined (low-medium tau and high tau) and low-medium tau (N = 76) subpopulations (LSM change difference: 4.43 and 3.99, representing 38.8% and 40.2% slowing of disease progression, respectively). Slowing of AD progression with donanemab was also observed for other clinical outcomes. Marked decreases in amyloid plaque and plasma phosphorylated tau 217 were observed; (< 24.1 Centiloids) was observed in 83.3% of the combined donanemab and 0% of the combined placebo groups. Amyloid-related imaging abnormalities of edema/effusions occurred in ten (22.2%) donanemab-treated participants (one [2.2%] symptomatic) and one (2.3%) placebo-treated participant.
CONCLUSIONS: The overall efficacy and safety of donanemab in Japanese participants were similar to the global TRAILBLAZER-ALZ 2 population.
Shoichiro Sato, Naohisa Hatakeyama, Hideaki Katagiri, and Shinji Fujikoshi are employees of Eli Lilly Japan K.K. and minor shareholders in Eli Lilly and Company. Sadao Katayama was an investigator in the TRAILBLAZER-ALZ 2 trial and has received lecture fees from Eli Lilly Japan K.K., Eisai Co., Ltd., and Kowa Pharmaceutical Industry Co., Ltd. John Sims is an employee of and minor shareholder in Eli Lilly and Company.
