This is the first large late-stage clinical trial to further support the amyloid hypothesis.
“The results were very consistent across imaging biomarkers, clinical endpoints and CSF biomarkers.”
At the 2018 Alzheimer’s Association International Conference in Chicago, Illinois, Lynn Kramer, MD, FAAN, Chief Clinical Officer and Chief Medical Officer at Eisai, presented 18-month data from the BAN2401 phase IIb clinical study, Study 201, that suggest BAN2401 may slow the pace of cognitive decline in Alzheimer patients and reverse the buildup of amyloid plaques thought to drive the disease’s neurodegeneration.
Though the trial failed to meet the study’s primary endpoint at 12 months, Kramer reported additional results on several of the trial’s secondary outcomes like reduction of amyloid plaques and improvement of cognition and function, though the trial was not intended to demonstrate efficacy in cognitive outcomes.
In the 18-month placebo-controlled, double-blind, parallel-group study, 856 patients with either mild cognitive impairment or early-stage Alzheimer disease and confirmed amyloid pathology in the brain were randomly assigned to placebo or 5 active treatment arms— 2.5 mg/kg biweekly, 5 mg/kg monthly, 5 mg/kg biweekly, 10 mg/kg monthly, and 10 mg/kg biweekly.
Researchers compared baseline changes on the primary efficacy measure, Alzheimer’s Disease Composite Score (ADCOMS) to placebo using a mixed model repeated measures model.
Kramer told NeurologyLive that the results were very consistent with imaging biomarkers, clinical endpoints and CSF biomarkers.
BAN2401 produced a statistically significant reduction in brain amyloid across all doses tested, with the highest dose of 10 mg/kg bi-weekly achieving an adjusted mean change from baseline versus placebo of -.26 (P <.0001) at 12 months and -.30 (P <.0001) at 18 months.
Additionally, a dose-dependent conversion from amyloid positive to negative was seen in 65% (P <.0001) and 81% (P <.0001) of subjects on the highest dose at 12 months at 18 months, respectively. A dose-dependent reduction (P = .011) was also produced in clinical decline compared to placebo, measured by ADCOMS, with the top dose significantly reducing decline by 35% (P = .027) and 30% (P = .034) at 12 and 18 months, respectively.
Kramer added that next steps include Eisai and Biogen reaching out to regulators in the US, Europe and Japan to discuss the results and next steps in terms of additional trials or even breakthrough status.