FDA Sets PDUFA Date on Aducanumab for Alzheimer Disease

August 7, 2020

Investigators found a 22% reduction in clinical decline at the 78-week cutoff in the intent to treat population in EMERGE who received high-dose aducanumab, with a similar reduction seen in the opportunity to complete population.

This article, "FDA Accepts Aducanumab for Review as Alzheimer Disease Treatment," was originally published in NeurologyLive.

The US Food and Drug Administration (FDA) has accepted a biologics license application with priority review for aducanumab, an investigational Alzheimer disease treatment.

There is currently a Prescription Drug User Fee Act target action date set for March 7, 2021.

Although the review is already on an accelerated track, the agency said it would act even earlier if the circumstances warrant it.

“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, chief executive officer at Biogen, said in a statement. “We believe that aducanumab marks the beginning of a new era of potential treatments for Alzheimer disease that will inspire even more discovery and innovation to bring hope to those affected by this devastating disease.”

The FDA also stated that it intends to soon hold an advisory committee meeting related to the application for the investigational human monoclonal antibody.

If approved, aducanumab, previously known as BIIB037, would become the first treatment for reducing clinical decline in Alzheimer disease through its mechanism of selectively targeting aggregated forms of amyloid-beta, including both soluble oligomers and insoluble fibrils.

The drug has faced an interesting journey on its road to the FDA. Data from the identical, phase 3 EMERGE and ENGAGE clinical trials have been the subject of much debate after an initial futility analysis completed in March 2019showed that the drug missed its primary end point.

However, results of an additional analysis of the EMERGE dataset announced in October 2019 reportedly showed statistically significant changes on the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score, with P values of .010 or .031 based on cutoff dates.

This analysis included an additional 3 months of data from patients who received a high dose of the drug.

At the time, Biogen said that although ENGAGE failed to meet its end points, data from patients in that trial who achieved sufficient exposure to high-dose aducanumab supported the findings from the EMERGE trial.

Notably, a 22% reduction in clinical decline was observed at the 78-week cutoff in the intent to treat population in EMERGE who received high-dose aducanumab, with a similar reduction seen in the opportunity to complete population.

Those treated with the drug also showed a consistent reduction in clinical decline as measured by prespecified secondary endpoints, including the Mini Mental State Exam (18% vs placebo; = .05), the Alzheimer’s Disease Assessment Scale-Cognitive Subscale 13 Items (27% vs placebo; P = .01), and the Alzheimer’s Disease Cooperative Study-Activities of Daily Living Inventory Mild Cognitive Impairment Version (40% vs placebo; P = .001).

In addition, imaging showed that both low- and high-dose aducanumab were associated with reduced amyloid plaque deposit burden at weeks 26 and 78 compared with placebo (P <.001).

Earlier this year, the FDA gave the go-ahead for a phase 3b redosing clinical trial of aducanumab in order to demonstrate long-term safety and tolerability in a targeted enrollment of 2400 patients from 4 previous clinical trial programs in the aducanumab development program.