Biogen and partner Eisai Co., Ltd. have submitted a Biologics License Application (BLA) to the U.S. FDA for aducanumab, an investigational treatment for Alzheimer's disease. The submission followed ongoing collaboration with the FDA and includes clinical data from the Phase III EMERGE and ENGAGE studies, as well as the Phase 1b PRIME study. Biogen has requested Priority Review. If approved, aducanumab would become the first therapy to reduce the clinical decline of Alzheimer's disease and would also be the first therapy to demonstrate that removing amyloid beta resulted in better clinical outcomes.
The Phase III trials demonstrated that patients who received aducanumab experienced significant slowing of decline on measures of cognition and function such as memory, orientation and language. Patients also experienced slowing of decline on activities of daily living including conducting personal finances, performing household chores, such as cleaning, shopping and doing laundry, and independently traveling out of the home.
EMERGE met its pre-specified primary endpoint, with patients 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% versus placebo). Patients treated with high dose aducanumab also showed a consistent reduction of clinical decline as measured by the pre-specified secondary endpoints: the Mini-Mental State Examination (MMSE; 18% versus placebo), the Alzheimer's Disease Assessment Scale-Cognitive Subscale 13 Items (ADAS-Cog 13; 27% versus placebo) and the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory Mild Cognitive Impairment Version (ADCS-ADL-MCI; 40% versus placebo). 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.
The PRIME study and its long-term extension (LTE) in patients with early Alzheimer's disease indicated that aducanumab reduced amyloid beta plaque in a dose- and time-dependent fashion, and analyses of exploratory clinical endpoints showed a reduction of clinical decline at 12 months, which continued out to 48 months in the LTE.