Aducanumab: Updated Ph Ib PRIME data

Data from 197 patients with prodromal or mild AD in the double-blind, dose-escalation, U.S. Phase Ib PRIME trial showed that 1, 3, 6 and 10 mg/kg IV aducanumab significantly reduced mean levels of amyloid plaque, as measured by florbetapir PET imaging using a composite standardized uptake value ratio (SUVR) of 6 regions of the brain, by 0.05 (p<0.05), 0.13 (p<0.001), 0.206 (p<0.001) and 0.263 (p<0.001) from baseline to week 54 vs. “virtually” no change for placebo. In a cohort of 23 carriers of the apolipoprotein E (APOE) epsilon 4 gene, dose titration with IV aducanumab up to 10 mg/kg significantly reduced mean amyloid plaque levels from baseline to week 54 by 0.171 (p<0.001).

Additionally, 10 mg/kg aducanumab led to a significantly slower cognitive decline, as measured by a smaller reduction in Clinical Dementia Rating Sum of Boxes (CDR-SB) score, at week 54 vs. placebo (0.63 vs. 1.89 points, p<0.05). The 1, 3 and 6 mg/kg doses of aducanumab reduced CDR-SB scores by 1.69, 1.33 and 1.09 points, respectively. In APOE epsilon 4 carriers, titration up to 10 mg/kg aducanumab reduced CDR-SB score by 0.7 points from baseline to week 54 (p<0.05 vs. placebo). Furthermore, 10 mg/kg aducanumab led to a significantly slower cognitive decline, as measured by a smaller reduction in Mini-Mental State Examination (MMSE) score, at week 52 vs. placebo (0.55 vs. 2.45 points, p<0.05). The 1, 3 and 6 mg/kg doses of aducanumab reduced MMSE scores by 2.21, 0.75 and 1.99 points, respectively. In APOE E4 allele carriers, titration up to 10 mg/kg aducanumab reduced MMSE score by 1 point from baseline to week 52. There were 3 deaths in the trial, none of which were considered treatment-related. The most common serious adverse event was amyloid-related imaging abnormalities-edema (ARIA-E), which occurred in 55% of APOE epsilon 4 carriers receiving the 10 mg/kg dose...