Donanemab shows promise in slowing Alzheimer’s disease progression
The antibody drug donanemab has demonstrated significant potential in slowing the progression of Alzheimer’s disease, according to new trial data that was presented at the 2023 Alzheimer’s Association International Conference and published in JAMA.
The trial, conducted across 277 medical research centers and hospitals in 8 countries, involved 1,736 participants with early symptomatic Alzheimer’s disease and amyloid and tau pathology.
Participants were randomly assigned to receive either donanemab or a placebo intravenously every 4 weeks for 72 weeks. To ensure the reliability of the results, the trial followed a double-blind, placebo-controlled design. To account for variations in tau pathology, participants were further divided into two groups: those with low/medium tau pathology and those with high tau pathology.
The primary outcome measured was the change in the integrated Alzheimer Disease Rating Scale (iADRS) score from baseline to 76 weeks, with lower scores indicating greater cognitive impairment. Out of the 24 outcomes assessed (including primary, secondary, and exploratory measures), 23 showed statistically significant results.
In the low/medium tau population, the least-squares mean (LSM) change in iADRS score at 76 weeks was -6.02 in the donanemab group and -9.27 in the placebo group, signifying a significant difference of 3.25. Similarly, in the combined population of low/medium and high tau pathology, the LSM change in iADRS score was -10.2 with donanemab and -13.1 with the placebo, displaying a difference of 2.92. These results indicate that donanemab treatment led to a significantly slower clinical progression of Alzheimer’s disease in both populations.
The Clinical Dementia Rating Scale (CDR-SB) score, another important metric, also showed positive results. In the low/medium tau population, the LSM change in CDR-SB score at 76 weeks was 1.20 with donanemab and 1.88 with the placebo, demonstrating a difference of -0.67. In the combined population, the LSM change was 1.72 with donanemab and 2.42 with the placebo, indicating a difference of -0.7.
Sims JR, Zimmer JA, Evans CD, et al. Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial. JAMA. Published online July 17, 2023. doi:10.1001/jama.2023.13239