Positive Results for Potential Alzheimer’s Disease Treatment in Phase 2 Trial
In one of the first late-stage studies to demonstrate potential disease modifying effects for the treatment of persons with Alzheimer’s disease, a monoclonal antibody to amyloid-ß protofibrils (BAN2401; Eisai, Woodcliff Lake, NJ and Biogen, Cambridge, MA) reduced patient’s amyloid-ß levels and slowed progression on their clinical measure Alzheimer’s disease (AD) Composite Score (ADCOMS).
In this phase 2 placebo-controlled, double-blind study, 856 subjects with mild cognitive impairment (MCI) due to AD or those diagnosed with mild AD (collectively early AD), who had confirmed amyloid-ß accumulation in their brain, were treated with 1 of 5 different doses of anti-amyloid-ß antibodies given biweekly or monthly or placebo. Clinical effects were measured with 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. The effect on amyloid-ß was measured with amyloid-positron emission tomography (amyloid-PET).
Subjects treated with the highest dose of anti-amyloid-ß antibodies (10 mg/kg biweekly) had a statistically significant slowing of disease progression as measured by their ADCOMS score after 18 months of treatment compared to those treated with placebo. Patients in this group also had statistically significant reductions in amyloid-PET standardized uptake value ratio (SUVR) and conversions from positive to negative for amyloid-ß in the brain on amyloid-PET imaging. Dose-dependent changes from baseline were observed across the PET results and the clinical endpoints and patients given the highest dose began to show statistically significant clinical benefits as measured by ADCOMS as early as 6 months and at 12 months.
Although as reported in December 2017, the trial did not reach a primary 12-month potential study endpoint, the final analysis at 18 months demonstrates a statistically significant slowing of disease progression on the key clinical endpoint (ADCOMS) after 12 months of treatment in patients receiving the highest treatment dose (10 mg/kg biweekly) as compared to placebo. Drug administration was generally well-tolerated, and the most common treatment emergent adverse events were infusion-related reactions and amyloid related imaging abnormalities (ARIA).
“The 18-month results of the BAN2401 trial are impressive and provide important support for the amyloid hypothesis,” said Jeff Cummings, MD, Founding Director, Cleveland Clinic Lou Ruvo Center for Brain Health. “I look forward to seeing the full data set shared with the broader Alzheimer’s community as we advance against this devastating disease.”