Biogen, Eisai Seek FDA Approval of Aducanumab for Alzheimer’s

Biogen and Eisai have submitted a biologics license application (BLA) to the U.S. Food and Drug Administration (FDA) requesting the approval of aducanumab (BIIB037) for the treatment of Alzheimer’s disease.

The submission, which was asking for priority review, had been pushed back earlier this year.

The agency now has 60 days to decide whether to accept the BLA for review, and if accepted, whether it will be carried out under the FDA’s priority review program.

If approved, aducanumab will become the first therapy with the potential to slow the clinical decline seen in patients with Alzheimer’s, as well as the first to demonstrate that reducing the buildup of amyloid plaques in the brain of patients may lead to better outcomes.

“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 [mechanism] of the disease,” Michel Vounatsos, CEO at Biogen, said in a press release. “We are committed to driving progress for the Alzheimer’s disease community and look forward to the FDA’s review of our filing.”

Aducanumab is an investigational treatment for Alzheimer’s that is currently being developed by Biogen in collaboration with Eisai. As a monoclonal antibody — a type of protein made in the laboratory that can bind to a substance in the body — the treatment is specifically designed to bind to the toxic clumps of beta-amyloid that are thought to be the underlying cause of neuronal degeneration in Alzheimer’s.

The BLA submission was based on data from two Phase 3 trials — EMERGE (NCT02484547) and ENGAGE (NCT02477800) — which assessed the efficacy of two doses of aducanumab in patients at early stages of the disease, who had mild cognitive impairment due to Alzheimer’s and mild Alzheimer’s dementia.

Both studies aimed to determine if monthly intravenous 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.

EMERGE met its primary goal, with patients given the highest dose of aducanumab experiencing a significant reduction in the progression of cognitive and functional impairments, assessed by changes in Clinical Dementia Rating-Sum of Boxes (CDR-SB score), compared with a placebo, at 78 weeks.

This was accompanied by significant reductions in other measures of clinical progression, including the Mini-Mental State Examination (MMSE) and the Alzheimer’s Disease Assessment Scale-Cognitive Subscale 13 Items, which were part of the study’s secondary goals.

Treatment also 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.

“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, MD, 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,” he added. “Aducanumab represents a potential breakthrough that we hope will provide a treatment foothold in the fight against Alzheimer’s disease.”

These benefits were also accompanied by a significant reduction in the number of amyloid plaques found in the brain of patients who received both doses of aducanumab, compared to those given a placebo, at weeks 26 and 78.

Although ENGAGE failed to meet its primary goal, Biogen stated that data from the sub-group of patients who had sufficient exposure to the highest dose of aducanumab also experienced significant benefits.

The BLA submission was also supported by data from the Phase 1b PRIME trial (NCT01677572), which evaluated the safety and tolerability of multiple doses of aducanumab, as well as its effects on the number of amyloid plaques, in patients with early Alzheimer’s.

Results from PRIME showed that treatment with aducanumab led to a dose- and time-dependent reduction in the number of amyloid plaques found in patients’ brains. In this trial, aducanumab also seemed to slow the progression of cognitive and functional impairments (assessed by CDR-SB and MMSE), when given at a dose of 10 mg/kg, starting at month 12 up to month 48 in the trial’s long-term extension study.

In addition to submitting the BLA to the FDA, Biogen is currently in discussions with other regulatory authorities worldwide, including in Europe and Japan, to prepare future submissions requesting the approval of aducanumab in these countries.