We report data from EMERGE (NCT02484547) and ENGAGE (NCT02477800), two Phase 3 studies of aducanumab in patients with early Alzheimer’s disease (MCI due to AD or mild AD dementia).

Aducanumab is a human monoclonal antibody that selectively targets aggregated forms of Aβ, including soluble oligomers and insoluble fibrils. EMERGE and ENGAGE are two 18-month, randomized, double-blind, placebo-controlled, global Phase 3 studies with identical design that evaluated the efficacy and safety of aducanumab in patients aged 50-85 years with early Alzheimer’s disease.

Key inclusion criteria included positive amyloid PET, MMSE score of 24-30, CDR-G of 0.5, and an RBANS-DMI score ≤85. During the 18-month placebo-controlled period, patients were randomized 1:1:1 to low-dose aducanumab, high-dose aducanumab, or placebo, administered via IV infusion every 4 weeks. The primary endpoint for EMERGE and ENGAGE was change from baseline at Week 78 on the CDR-SB. Secondary endpoints included change from baseline on MMSE, ADAS-Cog13, and ADCS-ADL-MCI. 

Following pre-planned futility analysis, analysis of a larger dataset showed that EMERGE met its primary endpoint, based on the pre-specified statistical analysis plan. Patients treated with high dose aducanumab showed a significant reduction of clinical decline from baseline in CDR-SB scores at 78 weeks (22% versus placebo, P=0.01). ENGAGE did not meet its primary endpoint. However, data from patients in ENGAGE who achieved sufficient exposure to high dose aducanumab supported the findings of EMERGE.

EMERGE met its primary endpoint, based on the pre-specified statistical analysis plan. Data from a subset of patients in ENGAGE support the results of EMERGE. The safety and tolerability profile of aducanumab in EMERGE and ENGAGE was consistent with previous studies of aducanumab.