The Food and Drug Administration (FDA) has accepted the biologics license application (BLA), agreeing to review aducanumab (BIIB037; Biogen, Cambridge, MA) as a potential treatment for Alzheimer disease (AD). If approved, aducanumab would become the first therapy approved to reduce the clinical decline of AD and to demonstrate that removing amyloid beta improves clinical outcomes. The application has been granted priority review, with a prescription drug user fee act (PDUFA) action date on March 7, 2021.
A priority review voucher was not used for the aducanumab BLA. The FDA also stated that it is planning to hold an advisory committee meeting for this application on a yet-to-be-determined date.
The application is based on data from the EMERGE (NCT02699463) and ENGAGE (NCT02477800) clinical trials, which were phase 3 multicenter randomized double-blind placebo-controlled parallel-group studies designed to evaluate the efficacy and safety of aducanumab. The studies evaluated the efficacy of monthly doses of aducanumab 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 with placebo on clinical decline. The EMERGE trial met the primary and secondary endpoint, the ENGAGE trial as a whole did not meet the prespecified primary endpoint. However, the post hoc analysis of a subset of participants in the ENGAGE trial provided supporting data for the EMERGE trial.
“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 AD,” said Michel Vounatsos, chief executive officer at Biogen. “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. We believe that aducanumab marks the beginning of a new era of potential treatments for AD that will inspire even more discovery and innovation to bring hope to those affected by this devastating disease.”
The most commonly reported adverse events were amyloid-related imaging abnormalities-edema (ARIA-E) and headache. The majority of those who had ARIA-E did not experience symptoms during ARIA-E, and episodes generally resolved within 4 to 16 weeks, typically without long-term clinical sequelae.
Bettina Balint, MD
Danielle S. Shpiner, MD; Crystal Dixon, MD; Melissa R. Ortega, MD; and Henry Moore, MD
Peter McAllister, MD