Aducanumab: Interim Phase Ib data

Interim data from 166 patients with prodromal or mild AD in the double-blind, dose-escalation, U.S. Phase Ib PRIME trial showed that 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 0.087, 0.143 and 0.205 from baseline to week 26 vs. almost no change for placebo (p<0.0001 for all). The 1 mg/kg dose of aducanumab led to a non-significant reduction in amyloid plaque of 0.03 vs. almost no change for placebo. At week 54, 3 and 10 mg/kg aducanumab significantly reduced amyloid plaque by 0.139 and 0.266 from baseline vs. placebo (p<0.001 for both). The 1 mg/kg dose of aducanumab led to a non-significant reduction in amyloid plaque of 0.056 at week 54, while the 6 mg/kg arm is ongoing with data only available up to week 30.

On exploratory endpoints, 3 and 10 mg/kg aducanumab led to significantly slower cognitive declines, as measured by smaller reductions in Mini-Mental State Examination (MMSE) scores, at 1 year vs. placebo (0.75 and 0.58 points, respectively, vs. 3.14 points, p<0.05 for both). The 1 mg/kg dose of aducanumab led to a 2.21 point reduction on the endpoint. Additionally, 10 mg/kg aducanumab led to a significantly slower cognitive decline, as measured by smaller reductions in Clinical Dementia Rating Sum of Boxes (CDR-SB) scores, at 1 year vs. placebo (0.59 vs. 2.04 points, p<0.05). The 1 and 3 mg/kg doses of aducanumab led to 1.7 and 1.33 point reductions on the endpoint, respectively. The most common treatment-related serious adverse event reported was amyloid-related imaging abnormalities. Data were presented at the International Conference on Alzheimer’s and Parkinson’s Diseases in Nice. ...