Eisai and Biogen have reported positive topline results from the Phase II study with BAN2401, an anti-amyloid beta protofibril antibody, in 856 patients with early Alzheimer’s disease.
This is the first late-stage study data successfully demonstrating potential disease-modifying effects on both clinical function and amyloid beta accumulation in the brain.
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-PET (positron emission tomography).
Study 201 is a placebo-controlled, double-blind, parallel-group, randomized study in 856 patients with mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) or mild Alzheimer’s dementia 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 (ADAS-Cog), the Clinical Dementia Rating Sum of Boxes (CDR-SB) scale and the Mini-Mental State Examination (MMSE) to enable sensitive detection of changes in early AD 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 (ADCOMS) 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 (SUVR) 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 6 months including at 12 months.
“This is the first late-stage anti-amyloid antibody study to successfully achieve statistically significant results at 18 months, further validating the amyloid hypothesis,” said Lynn Kramer, Chief Clinical Officer and Chief Medical Officer, Neurology Business Group, Eisai.
“The prospect of being able to offer meaningful disease-modifying therapies to individuals suffering from this terrible disease is both exciting and humbling,” said Alfred Sandrock, Executive Vice President and Chief Medical Officer at Biogen.
“These BAN2401 18-month data offer important insights in the investigation of potential treatment options for patients with Alzheimer’s disease and underscores that neurodegenerative diseases may not be as intractable as they once seemed.”