Eisai Co., Ltd. and Biogen Inc. announced positive topline results from the Phase II study with BAN2401, an anti-amyloid beta protofibril antibody, in 856 patients with early Alzheimer’s disease.
The study achieved statistical significance on key predefined endpoints evaluating efficacy at 18 months on slowing progression in Alzheimer’s Disease Composite Score (ADCOMS) and on reduction of amyloid accumulated in the brain as measured using amyloid-positron emission tomography (PET).
Study 201 (ClinicalTrials.gov identifier NCT01767311) is a placebo-controlled, double-blind, parallel-group, randomized study in 856 patients with mild cognitive impairment due to Alzheimer’s disease or mild Alzheimer’s dementia (collectively known as early Alzheimer’s disease) with confirmed amyloid pathology in the brain.
Efficacy was evaluated at 18 months by predefined conventional statistics on ADCOMS, which combines items from the Alzheimer’s Disease Assessment Scale-cognitive subscale, the Clinical Dementia Rating Sum of Boxes scale, and the Mini-Mental State Examination to enable sensitive detection of changes in early Alzheimer’s disease symptoms. Patients were randomized to five dose regimens, 2.5 mg/kg biweekly, 5 mg/kg monthly, 5 mg/kg biweekly, 10 mg/kg monthly and 10 mg/kg biweekly, or placebo.
Topline results of the final analysis of the study demonstrated a statistically significant slowing of disease progression on the key clinical endpoint after 18 months of treatment in patients receiving the highest treatment dose (10 mg/kg biweekly) as compared to placebo.
Results of amyloid PET analyses at 18 months, including reduction in amyloid PET standardized uptake value ratio and amyloid PET image visual read of subjects converting from positive to negative for amyloid in the brain, were also statistically significant at this dose. Dose-dependent changes from baseline were observed across the PET results and the clinical endpoints. Further, the highest treatment dose of BAN2401 began to show statistically significant clinical benefit as measured by ADCOMS as early as six months including at 12 months.
BAN2401 demonstrated an acceptable tolerability profile through 18 months of study drug administration. The most common treatment emergent adverse events were infusion-related reactions and Amyloid Related Imaging Abnormalities (ARIA). Infusion related reactions were mostly mild to moderate in severity. Incidence of ARIA-E (edema) was not more than 10 percent in any of the treatment arms, and less than 15 percent in patients with ApoE4, a strong genetic risk factor for late-onset Alzheimer disease, at the highest dose per the study protocol safety and reporting procedures.
Detailed results of the study will be presented at future academic conferences.
(Source: Eisai Co., Ltd.)
Filed Under: Drug Discovery