Biogen says highest dose of BAN2401 showed slowing of clinical decline of 30%
Eisai and Biogen announced detailed results from the Phase 2 study with BAN2401, an anti-amyloid beta protofibril antibody, in 856 patients with early Alzheimer's disease as part of Session DT-01 "Recent Developments in Therapeutics" at the Alzheimer's Association International Conference being held in Chicago, Illinois. Through Bayesian interim analyses, the highest doses of 10 mg/kg monthly and 10 mg/kg biweekly were determined to be the treatment dosages with higher efficacy early in the trial, and as a result, the proportion of patients allocated to these treatment arms was greater. Following a regulatory request, outside of the United States, in July 2014, the allocation of APOE4 carriers to the 10 mg/kg biweekly treatment arm was restricted, resulting in fewer APOE4 carriers in this arm and more patients being allocated to the 10 mg/kg monthly treatment arm. BAN2401 demonstrated a dose-dependent reduction in amyloid plaques as measured by amyloid PET, and this reduction was statistically significant at all doses. At the highest dose of BAN2401 of 10 mg/kg biweekly, an analysis of amyloid accumulated in the brain using standardized PET as measured on the Centiloid scale showed an observed mean at baseline of 74.5 and at 18 months of 5.5. Using a Mixed-effects Model with Repeated Measures, the mean reduction in amyloid load was 70 units, which was statistically significant. In amyloid PET image visual read, BAN2401 demonstrated a dose dependent conversion from amyloid positive to negative, and at the highest dose, 81% of patients converted from amyloid positive to negative at 18 months. Conventional statistical methods on predefined clinical endpoints at the 18 month final efficacy time point confirmed a dose-dependent slowing in cognitive decline from baseline on ADCOMS. The highest treatment dose of 10 mg/kg biweekly demonstrated a statistically significant slowing of clinical decline of 30% compared to placebo at 18 months. A statistically significant slowing of decline on ADCOMS was observed as early as 6 months as well as at 12 months. Dose-dependent slowing in cognitive decline from baseline on ADAS-Cog was also observed for BAN2401, with the highest treatment dose of BAN2401 demonstrating a significant slowing of clinical decline compared to placebo at 18 months. Furthermore, dose-dependent slowing in cognitive decline from baseline on CDR-SB was observed, surpassing the pre-specified difference of 25% over the duration of the study. At 18 months, slowing of clinical decline for the highest treatment dose of BAN2401 compared to placebo on CDR-SB was 26%. The rate of clinical decline for the placebo group was consistent with the results of research by the Alzheimer's Disease Neuroimaging Initiative in the United States.