On 18 March, data from the pivotal Phase III EMERGE and ENGAGE trials for aducanumab were published in the Journal of Prevention of Alzheimer’s Disease (JPAD). The peer-reviewed manuscript includes results from the primary, secondary and tertiary endpoints in the trials, as well as safety data and biomarker sub-studies. Aducanumab is a monoclonal antibody treatment that targets amyloid beta proteins in the brain, leading to clearance of these damaging proteins by the immune system. The randomised, double-blind and placebo-controlled ENGAGE and EMERGE Phase III clinical trials investigated the efficacy and safety of aducanumab in participants with mild cognitive impairment and mild dementia due to Alzheimer’s disease (AD), delivering aducanumab or a placebo to participants via intravenous infusion once every 4 weeks over 76 weeks. These studies involved 348 sites in 20 countries. Both trials were halted early based on results from a futility analysis of interim data, pooled from the first approximately 50% of enrolled participants.
The primary endpoint was met in EMERGE but not ENGAGE (CDR-SB, an integrated scale that assesses both function and cognition). In EMERGE, high- dose aducanumab demonstrated a difference of -0.39 vs placebo in the mean change from baseline in CDR-SB score at week 78, a 22% reduction in decline. Data from EMERGE demonstrated a statistically significant change across all four primary and secondary clinical endpoints. ENGAGE did not meet its primary or secondary endpoints. A dose-and time-dependent reduction in pathophysiological markers of AD was observed in both trials. These sub studies showed a dose- and time-dependent reduction in amyloid PET SUVR. Reductions in plasma p-tau181 levels were positively correlated with reductions in amyloid PET SUVR at week 78. The most common adverse event was amyloid-related imaging abnormalities-edema.
