Biogen announces detailed results from Phase 2 study of elenbecestat
Eisai and Biogen announced detailed results from a Phase 2 clinical study of the investigational oral BACE inhibitor elenbecestat at the Alzheimer's Association International Conference 2018 being held in Chicago. The multicenter, randomized, double-blind, placebo-controlled parallel-group 18-month Phase 2 clinical study was conducted in the United States in patients with mild cognitive impairment due to Alzheimer's disease, or mild to moderate dementia due to Alzheimer's disease with confirmed amyloid pathology by positron emission tomography. Seventy patients were randomized to four treatment arms receiving elenbecestat or placebo daily. During the study period, more than half the patients in the elenbecestat 5 mg and 15 mg arms were switched to the 50 mg arm. These patients received elenbecestat 50 mg for three months or longer. Analysis was carried out on the combination of patients in the initial 50 mg treatment arm plus the patients switched to the 50 mg arm, referred to collectively as the "50 mg total group arm". In addition to the primary safety objective, the study assessed amyloid pathology in the brain at 18 months as measured by amyloid PET as well as efficacy in terms of clinical symptoms, which were exploratory objectives in this study. Regarding the accumulation of amyloid in the brain at 18 months as measured by PET via quantitative evaluation of Standard Uptake Value Ratio using the florbetaben PET tracer, a statistically significant reduction of brain amyloid load as compared to placebo was observed in the 50 mg total group arm with a reduction in SUVr of 0.104. Although a small sample size, using the florbetapir PET tracer demonstrated a statistically significant decrease in brain amyloid load compared to placebo for the 50 mg total group arm at 18 months. Clinical efficacy was evaluated using the Clinical Dementia Rating Sum of Boxes rating scale. After 18 months of treatment, clinical assessment using CDR-SB demonstrated a mean treatment difference of -0.5 based off of an increase of 1.1 for the elenbecestat 50 mg total group arm versus an increase of 1.6 for the placebo group. This represented a 31% slowing in rate of decline for the elenbecestat arm which is potentially considered to be clinically important. "While the study was not powered to show statistical significance compared to placebo on clinical symptoms, the results suggest that elenbecestat could slow decline in cognitive function of patients with MCI due to Alzheimer's disease, or mild to moderate dementia due to Alzheimer's disease," the companies stated.