Biogen and Eisai Co., Ltd. announced results from a recent analysis of the ongoing long-term extension (LTE) Phase 1b study of aducanumab, an investigational treatment for mild cognitive impairment (MCI) due to Alzheimer's disease (AD) and mild AD dementia. The updated analyses include data from the placebo-controlled period and LTE for patients treated with aducanumab up to 36 months in the titration cohort and up to 48 months in the fixed-dose cohorts. The results are generally consistent with previous interim analyses, and there were no changes to the risk-benefit profile of aducanumab.
The Phase 1b study is a randomized, double-blind, placebo-controlled, multiple-dose study evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and clinical effects of aducanumab in patients with prodromal AD or mild AD dementia. The study includes fixed dosing at 1, 3, 6 and 10 mg/kg as well as an arm with a titration regimen in which patients received a gradually increased dose of aducanumab until they reach a maximum dose of 10 mg/kg.
In the Phase 1b study 196 patients received aducanumab or placebo, of which 143 patients entered the LTE. The LTE cohorts were allocated across six dosing arms including: placebo switchers, 1 mg/kg switchers to 3 mg/kg, fixed doses (3 mg/kg, 6 mg/kg, 10 mg/kg) and titration. Additionally, there were discontinuations as expected in studies of 36 or more months. As a result, there are small patient numbers in the new analyses.
The results for each dose arm are generally consistent with previous interim analyses. Amyloid plaque levels as measured by positron emission tomography (PET) continued to decrease in a dose- and time- dependent manner in patients from the titration cohort at 36 months and fixed-dose cohorts at 48 months. Amyloid plaque levels in the 10 mg/kg fixed-dose at 48 months remained at a level considered below the quantitative cut point that discriminates between a positive and negative scan. Analyses of exploratory clinical endpoints Clinical Dementia Rating Sum of Boxes (CDR-SB) and the Mini-Mental State Examination (MMSE) suggest a continued benefit on the rate of clinical decline over 36 months and 48 months, respectively. Clinical effects with titrated aducanumab in the second year of the LTE were generally consistent with findings in the 10 mg/kg fixed-dose cohorts.
Of the 185 patients dosed with aducanumab in the Phase 1b study, 46 patients experienced amyloid imaging abnormalities (ARIA)-E (edema). Eight patients experienced more than one episode of ARIA-E. The majority of ARIA events occurred early in the course of treatment; they were typically mild radiographically (MRI), clinically asymptomatic and resolved or stabilized within 4-12 weeks, with most patients continuing treatment. In the Phase 1b LTE, the most commonly reported adverse events were headache, fall and ARIA.