After 18 months of treatment, Study 201 participants at the highest treatment dose demonstrated a statistically significant slowing of cognitive decline of 30% compared to placebo.
Eisai and Biogen today announced results from a phase 2 study (Study 201) of BAN2401, an anti-amyloid beta (Aβ) protofibril antibody, in patients with early Alzheimer disease at the Alzheimer’s Association International Conference (AAIC) 2018 in Chicago.
At 18 months, the highest tested treatment dose of 10 mg/kg twice a month demonstrated a significant slowing of cognitive decline of 30% compared to placebo (p = 0.034) as measured by the Alzheimer's Disease Composite Score (ADCOMS).
"The detailed results of BAN2401 Phase 2b clinical study are very encouraging showing consistent effects on several efficacy measurements as well as biomarkers including PET combined with a good tolerability profile," said Gunilla Osswald, PhD, CEO, BioArctic AB, a Swedish research-based biopharma company that worked with Eisai to develop BAN2401.
Study 201 is a placebo-controlled, double-blind, randomized clinical study of 856 participants with mild cognitive disorder (MCI) due to Alzheimer disease, or mild Alzheimer dementia. All participants had confirmed amyloid pathology in the brain.
Participants were randomized to 1 of 6 study arms: 2.5mg/kg biweekly, 5 mg/kg
monthly, 5 mg/kg biweekly, 10 mg/kg monthly, and 10 mg/kg biweekly, or placebo. Using a Bayesian Adaptive Randomization Design, the study automatically placed newly enrolled study participants into treatment arms demonstrating higher probability of efficacy based on the analysis of interim data.
The study measured changes from baseline to 18 months in biomarkers of Alzheimer pathophysiology, including amyloid accumulation in the brain as measure by amyloid positron emission tomography (PET). Additionally, the clinical endpoints of Alzheimer’s Disease Composite Score (ADCOMS), Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) and Clinical Dementia Rating Sum of Boxes (CDR-SB) were measured from baseline to 18 months of treatment.
In addition to the slowing of cognitive decline on ADCOMS observed at 18 months, a statistically significant slowing of decline on ADCOMS was measured at 12 months (p <0.05) and even as early as 6 months (p <0.05).
Dose-dependent slowing on ADAS-Cog was also observed, with the highest treatment dose of BAN2401 showing a slowing of cognitive decline of 47% compared to placebo at 18 months (p = 0.017).
Amyloid accumulation in the brain measured by amyloid PET showed statistically significant and dose-dependent effects for all BAN2401 dosage groups compared to placebo at 18 months. For the highest dose group, using standardized PET as measured at the Centiloid scale, the mean reduction in accumulated amyloid in the brain was 70 units at 18 months based on Mixed-effects Model with Repeated Measures (p <0.0001). The observed baseline mean was 74.5 units and observed 18-month mean was 5.5 units.
Additionally, in the amyloid PET visual measurement, 81% of participants in the highest dose group converted from amyloid positive to negative at 18 months (p <0.0001).
Throughout the 18 months of the study, the incidence rate of treatment-related adverse events was 26.5% for the placebo arm, 53.4% for the 10 mg/kg monthly treatment arm, and 47.2% for the 10 mg/kg biweekly treatment arm. The most common of these were Amyloid Related Imaging Abnormalities (ARIA) (9.9% for the 10 mg/kg biweekly group) and infusion-related reactions. All patients with ARIA-E identified by MRI were discontinued in the study, according to protocol.
The incidence rate of serious adverse events was 17.6% for the placebo arm, 12.3% for the 10 mg/kg monthly treatment arm and 15.5% for the 10 mg/kg biweekly arm.
“These results are important for BioArctic, the Alzheimer field of research, and give new hope for patients and their families," said Osswald.