Baseline Characteristics From ENGAGE and EMERGE: Two Phase 3 Studies to Evaluate Aducanumab in Patients With Early Alzheimer’s Disease (P4.1-001)

Objective: We describe baseline characteristics from ENGAGE (NCT02477800) and EMERGE (NCT02484547), ongoing Phase 3 studies of similar designs evaluating aducanumab in patients with early AD (MCI due to AD or mild AD dementia). Background: Aducanumab is a human monoclonal antibody that binds to both soluble and insoluble aggregated forms of Aβ, including oligomers, protofibrils, and fibrils. ENGAGE and EMERGE are randomized, placebo-controlled, multinational Phase 3 studies evaluating the efficacy and safety of aducanumab in patients aged 50–85 years who meet clinical criteria for MCI due to AD or mild AD dementia. Design/Methods: Key inclusion criteria included positive amyloid PET scan, MMSE score of 24–30, CDR-G of 0.5, and an RBANS-DMI score ≤85. During the 18-month placebo-controlled period, patients are randomized 1:1:1 to low-dose aducanumab (titration to 3 or 6 mg/kg based on ApoE ɛ4 carrier status), high-dose aducanumab (titration to 10 mg/kg), or placebo; administration was iv infusion every 4 weeks. After completion of the placebo-controlled period, patients may enter a long-term extension during which all patients receive aducanumab. The primary endpoint for ENGAGE and EMERGE is change from baseline at week 78 on the CDR-SB. Secondary endpoints include change from baseline on MMSE, ADAS-Cog13, and ADCS-ADL-MCI. Results: ENGAGE and EMERGE are now fully enrolled; 1647 (ENGAGE) and 1638 (EMERGE) patients were randomized and received ≥1 dose of study medication. Approximately half the patients in both studies were women (52.4%, ENGAGE; 51.5%, EMERGE). The majority of patients in both trials were diagnosed with MCI due to AD at baseline (80%, ENGAGE; 82%, EMERGE). MMSE mean (standard deviation [SD]) score at baseline was 26.4 (1.76) for ENGAGE and 26.3 (1.72) for EMERGE. Conclusions: Baseline characteristics are similar across the ENGAGE and EMERGE trials and are representative of patients with early AD. Disclosure: Dr. Von Hehn has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Von Hehn has received personal compensation in an editorial capacity for Biogen. Dr. Von Rosenstiel has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Von Rosenstiel holds stock and/or stock options in Biogen. Dr. Tian has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Tian has received personal compensation in an editorial capacity for Biogen. Dr. Wu has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Wu has received personal compensation in an editorial capacity for Biogen. Dr. Chen has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Biogen. Dr. Chen has received personal compensation in an editorial capacity for Shareholder of Biogen. Dr. Skordos has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Skordos has received personal compensation in an editorial capacity for Biogen. Dr. Harrison has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Harrison has received personal compensation in an editorial capacity for Biogen. Dr. Prada has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Prada holds stock and/or stock options in Biogen. Dr. Chalkias has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Chalkias holds stock and/or stock options in Biogen. Dr. Rajagovindan has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Rajagovindan holds stock and/or stock options in Biogen. Dr. Aisen has nothing to disclose. Dr. Salloway has nothing to disclose. Dr. Budd Haeberlein has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Budd Haeberlein holds stock and/or stock options in Biogen. Dr. Sandrock has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Sandrock holds stock and/or stock options in Biogen.