Biogen and Eisai Co., Ltd. (Tokyo, Japan) today announced that Biogen has completed the submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for the approval of aducanumab, an investigational treatment for Alzheimer’s disease. The completed submission followed ongoing collaboration with the FDA and includes clinical data from Phase 3 EMERGE and ENGAGE studies, as well as the Phase 1b PRIME study. As part of the completed submission, 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.

“Alzheimer’s disease remains one of the greatest public health challenges of our time. It robs memories, independence and eventually the ability to perform basic tasks from the people we love,” said Michel Vounatsos, Chief Executive Officer at Biogen. “The aducanumab BLA is the first filing for FDA approval of a treatment that addresses the clinical decline associated with this devastating condition, as well as the pathology of the disease. We are committed to driving progress for the Alzheimer’s disease community and look forward to the FDA’s review of our filing.”

“People living with Alzheimer’s, their families, caregivers and so many others in the community are fighting this disease every day, and the global social burden of the disease is expected to grow as the population ages,” said Dr. Haruo Naito, Chief Executive Officer at Eisai Co., Ltd. “The BLA submission is an important step in the fight against this disease, for which pathophysiological progression currently cannot be stopped, delayed, or prevented.”

The aducanumab clinical development program included two Phase 3 trials, EMERGE and ENGAGE, in patients with early-stage Alzheimer’s disease (enrolled patients had mild cognitive impairment (MCI) due to Alzheimer’s disease and mild Alzheimer’s disease dementia with Mini-Mental State Examination (MMSE) scores of 24-30). In EMERGE, patients who received aducanumab experienced significant slowing of decline on measures of cognition and function such as memory, orientation and language. Patients also experienced a slowing of decline in 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 (n=1,638) 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, P=0.01). In EMERGE, 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, P=0.05), the Alzheimer’s Disease Assessment Scale-Cognitive Subscale 13 Items (ADAS-Cog 13; 27% versus placebo, P=0.01) and the Alzheimer’s Disease Cooperative Study-Activities of Daily Living Inventory Mild Cognitive Impairment Version (ADCS-ADL-MCI; 40% versus 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, Biogen believes a subset of data from ENGAGE is supportive of the outcome in EMERGE.

The aducanumab clinical program also included the Phase 1b PRIME study and its long-term extension (LTE) in patients with early Alzheimer’s disease (enrolled patients had prodromal Alzheimer’s disease or mild Alzheimer’s disease dementia with MMSE scores of 20-30). The results of this study 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 (CDR-SB and MMSE, nominally statistically significant for the 10 mg/kg dose at 12 months), which continued out to 48 months in the LTE.

“For many people living with the early stages of Alzheimer’s disease, maintaining independence for as long as possible is the ultimate goal,” said Stephen Salloway, M.D., M.S., Director of the Butler Hospital Memory and Aging Program at Brown University. “If we can help slow the progression from one stage to the next, this could preserve independence, which, in turn, could have truly meaningful benefits for people living with the disease and their loved ones. Aducanumab represents a potential breakthrough that we hope will provide a treatment foothold in the fight against Alzheimer’s disease.”

The completion of the BLA submission followed a planned pre-BLA meeting with the FDA. The FDA now has up to 60 days to decide whether to accept the application for review, at which point, if accepted, Biogen expects the FDA will also inform the Company whether the BLA has been granted Priority Review designation. The BLA will then be subject to review by the FDA to make a determination on the potential approval of aducanumab.

In addition to submitting the BLA to the FDA, Biogen has continued to engage in dialogue with regulatory authorities in other markets, including Europe and Japan, working diligently toward the goal of submitting applications in these markets.

Aducanumab (BIIB037) is an investigational human monoclonal antibody studied for the treatment of Alzheimer’s disease. Based on clinical data, aducanumab has the potential to impact underlying disease pathophysiology, slow cognitive and functional decline and provide benefits on patients’ ability to perform 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. If approved, aducanumab would be the first treatment to meaningfully change the course of the disease for individuals living with Alzheimer’s.

Biogen licensed aducanumab from Neurimmune under a collaborative development and license agreement. Since October 2017 Biogen and Eisai have collaborated on the development and commercialization of aducanumab globally.

EMERGE and ENGAGE were Phase 3 multicenter, randomized, double-blind, placebo-controlled, parallel-group studies designed to evaluate the efficacy and safety of aducanumab. The primary objective of the studies was to evaluate the efficacy of monthly doses of aducanumab as compared with placebo in reducing cognitive and functional impairment as measured by changes in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score. Secondary objectives were to assess the effect of monthly doses of aducanumab as compared to placebo on the clinical decline as measured by the Mini-Mental State Examination (MMSE), Alzheimer’s Disease Assessment Scale-Cognitive Subscale 13 Items (ADAS-Cog 13) and Alzheimer’s Disease Cooperative Study-Activities of Daily Living Inventory Mild Cognitive Impairment Version (ADCS-ADL-MCI).