The U.S. Food and Drug Administration (FDA) has accepted and given priority review designation to Biogen‘s application requesting the approval of aducanumab (BIIB037) for the treatment of Alzheimer’s disease.
While the Prescription Drug User Fee Act (PDUFA) action date is set for March 7, 2021 — meaning a decision is due by then — the agency said it plans to act early on this application under an expedited review. An advisory committee meeting is in the FDA’s plans for discussing this application, though no date has yet been set.
The supplemental biologics license application (BLA) was based on data from two Phase 3 trials — EMERGE (NCT02484547) and ENGAGE (NCT02477800) — and from the Phase 1b PRIME trial (NCT01677572). That data demonstrated that aducanumab significantly slows cognitive decline and helps patients live an independent life for longer periods.
If approved, aducanumab will become the first therapy with the potential to slow clinical decline in Alzheimer’s patients, as well as the first to demonstrate that reducing the buildup of toxic amyloid plaques in the brain leads to better outcomes.
“The FDA’s acceptance of the aducanumab BLA with Priority Review is an important step in the path to potentially having a treatment that meaningfully changes the course of Alzheimer’s disease,” Michel Vounatsos, CEO at Biogen, said in a press release.
“We look forward to working with the FDA throughout the review process and thank the thousands of clinicians, patients and caregivers who participated in our clinical trials and have accompanied us on this journey,” Vounatsos said. “We believe that aducanumab marks the beginning of a new era of potential treatments for Alzheimer’s disease that will inspire even more discovery and innovation to bring hope to those affected by this devastating disease.”
Developed by Biogen and Eisai, aducanumab is an investigational human monoclonal antibody that works by targeting toxic clumps of amyloid beta, thought to be the underlying cause of Alzheimer’s. It targets a particular region of the protein that is only accessible in these toxic aggregates or clumps, leaving the functional amyloid beta proteins unharmed.
EMERGE and ENGAGE were two randomized, double-blind trials that evaluated two doses of aducanumab in people with mild cognitive impairment due to the neurodegenerative disease and mild Alzheimer’s dementia.
Both studies sought to determine if monthly intravenous (into-the-vein) infusions of aducanumab, over a period of 18 months, could slow the progression of cognitive and functional impairment — including loss of memory, orientation, and language — compared with a placebo.
The trials were halted after a monitoring committee said aducanumab was not likely to produce meaningful benefits for patients. However, a later analysis ultimately showed that EMERGE met its primary goal: compared with those given a placebo, participants on the highest dose of aducanumab experienced a significantly smaller decline in cognitive and functional status over 18 months, assessed by changes in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) scores.
Secondary measures of cognitive functioning, including the Mini-Mental State Examination (MMSE) and the Alzheimer’s Disease Assessment Scale-Cognitive Subscale 13 Items, also were significantly better for EMERGE participants who received high-dose aducanumab.
The treatment also significantly slowed the rate at which patients lost their ability to perform daily life activities, including managing their personal finances, performing household chores, and traveling independently.
In ENGAGE, the progression of clinical and functional impairments was not significantly slowed in the overall population. But an analysis of patients who had sufficient exposure to high-dose aducanumab did show significant benefits over a placebo, supporting the findings from EMERGE.
In the two trials, both doses of aducanumab also were accompanied by a significant reduction in the amount of amyloid plaques found in the patients’ brains.
The safety profile of aducanumab was consistent with prior studies. The most commonly reported adverse events were amyloid-related imaging abnormalities-edema, which usually resolved within one to four months without causing symptoms, and headaches.
The earlier PRIME trial had evaluated the safety and tolerability of multiple doses of aducanumab, as well as its effects on the amount of amyloid beta, in people with early Alzheimer’s. The results also demonstrated a significant reduction in brain amyloid plaques and showed evidence that aducanumab slows the progression of cognitive and functional impairments.
“Reducing clinical decline and maintaining the ability to live an independent life for as long as possible are things that people living with Alzheimer’s disease and their families value in a potential treatment,” said Haruo Naito, CEO at Eisai.
“If aducanumab is approved, we expect that it will make a difference in the lives of people living with Alzheimer’s disease. We believe that this historic milestone is one step towards creating a paradigm shift in treatment for Alzheimer’s disease, a public health issue for aging societies,” he added.
“Today, I am heartened by what this progress may mean for people living with Alzheimer’s disease and their families,” said Christopher van Dyck, MD, director of the Yale Alzheimer’s Disease Research Center. “If aducanumab is determined to be effective in reducing the decline in cognition and activities of daily living resulting from progression of this disease by addressing the underlying disease pathology, it will deliver meaningful benefits to those who most need them.”
Biogen and Eisai also are in discussions with regulatory agencies in Europe and Japan to file applications for the approval of aducanumab in those countries.
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