The biologics license application (BLA) for the approval of aducanumab (BIIV037; Biogen, Cambridge, MA) was submitted to the Food and Drug Administration (FDA), for treatment for Alzheimer disease (AD). The completed submission followed ongoing collaboration with the FDA and includes clinical data from the phase 3 Emerge (NCT02484547) and Engage (CT02477800) studies, as well as the phase 1b prime study.
The aducanumab clinical development program included 2 phase 3 trials, Emerge and Engage, in individuals with early stage AD. Enrolled participants had mild cognitive impairment (MCI) caused by AD or mild AD dementia with MiniMental State Examination (MMSE) scores of 24 to 30. In Emerge, participants who received aducanumab experienced significant slowing of decline on measures of cognition and function such as memory, orientation, and language. Participants also experienced slowing of decline on activities of daily living including conducting personal finances, performing household chores (eg, cleaning, shopping, and doing laundry), and independently traveling out of the home.
Emerge (n=1,638) met its prespecified primary endpoint, with participants treated with high dose aducanumab showing a statistically significant reduction of clinical decline from baseline in Clinical Dementia Rating-Sum of Boxes (CDR-SB) scores at 78 weeks (22% vs placebo, P=0.01). In Emerge, participants treated with high dose aducanumab also showed a consistent reduction of clinical decline as measured by the prespecified secondary endpoints: the MiniMental state examination (MMSE; 18% vs placebo, P=0.05), the AD assessment scale-Cognitive Subscale 13 Items (ADAS-Cog 13; 27% vs placebo, P=0.01) and the AD Cooperative Study-activities of daily living inventory mild cognitive impairment version (ADCS-ADL-MCI; 40% vs placebo, P=0.001). Imaging of amyloid plaque deposition in Emerge demonstrated that amyloid plaque burden was reduced with low and high dose aducanumab compared to placebo at 26 and 78 weeks (P<0.001). While Engage (n=1,647) did not meet its primary endpoint, the manufacturer believes a subset of data from Engage are supportive of the outcome in Emerge.
David Z. Rose, MD
Shailee S. Shah, MD, and Andrew McKeon, MD