Positive Phase 2 Results for Novel Alzheimer Disease Treatment BAN2401

Initial data from Study 201, as announced in December 2017, showed BAN2401 did not meet the primary endpoint.
Initial data from Study 201, as announced in December 2017, showed BAN2401 did not meet the primary endpoint.
The following article is part of conference coverage from the 2018 Alzheimer's Association International Conference in Chicago, Illinois. Neurology Advisor's staff will be reporting breaking news associated with research conducted by leading experts in neurology. Check back for the latest news from AAIC 2018.

CHICAGO — Researchers form Eisai Co. and Biogen, Inc. presented positive phase 2 clinical data for BAN2401 regarding secondary endpoints of amyloid plaque reduction and improvement of cognition and function in patients with Alzheimer disease. The data were presented at the 2018 Alzheimer's Association International Conference, July 22-26, 2018 in Chicago, Illinois. 

BAN2401, a humanized monoclonal antibody, binds with high selectivity to soluble aggregated Aβ, such as protofibrils. Study 201 (N=856) was an 18-month placebo-controlled, double-blind, parallel-group study. Patients with early Alzheimer disease (with confirmed amyloid pathology in the brain) were randomly assigned to placebo or 5 active treatment arms. Study authors compared changes from baseline on the primary efficacy measure, Alzheimer's Disease Composite Score (ADCOMS), to placebo using a mixed model repeated measures (MMRM) model.

Initial data from Study 201, as announced in December 2017, showed BAN2401 did not meet the primary endpoint. However, new data reported today on the trial's secondary endpoints showed that BAN2401 exerted dose-dose-dependent effects on amyloid PET, clinical endpoints, and tau CSF biomarkers.

Specifically, treatment with BAN2401 demonstrated a statistically significant reduction in brain amyloid for all evaluated doses; the highest dose of 10 mg/kg biweekly achieved an adjusted mean change from baseline of -0.26 at 12 months (P <.0001) and -0.30 at 18 months (P <.0001) compared with placebo. In addition, a dose-dependent conversion from amyloid positive to negative was seen in 65% of patients at 12 months (P <.0001) and in 81% of patients at 18 months (P <.0001) at the highest dose.

Regarding reduction of clinical decline, BAN2401 showed a dose-dependent reduction (P =.011) vs placebo as measured by ADCOMS; the 10 mg/kg dose significantly reduced clinical decline by 35% at 12 months (P =.027) and by 30% at 18 months (P =.034).

Infusion-related reactions (mostly mild to moderate) and amyloid related imaging abnormalities (ARIA) were the most common treatment-related adverse events.

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Based on the findings, the authors concluded, "Treatment with BAN2401 produced a dose-dependent substantial reduction in brain amyloid plaque at the 10mg/kg biweekly dose, which resulted in the majority of subjects converting to amyloid negative as determined by PET visual read. These results were accompanied by significant reduction in clinical decline compared to placebo as measured by the ADCOMS." Data from this late-stage study further support the amyloid hypothesis, they added.

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Reference

Swanson CJ, Zhang Y, Dhadda S, et al. Treatment of early AD subjects with BAN2401, an anti-Aβ protofibril monoclonal antibody, significantly clears amyloid plaque and reduces clinical decline. Presented at: 2018 Alzheimer's Association International Conference. July 22-26, 2018; Chicago, IL. Oral presentation DT-01-07.