A PDUFA date has been scheduled for March 7, 2021, but the agency said it would consider an even more expedited review if warranted.
Nearly 1 month after filing its biologics license application for its investigational Alzheimer disease treatment aducanumab,1 Biogen has announced that the FDA has accepted the application with priority review, setting a Prescription Drug User Fee Act target action date of March 7, 2021.2
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,” said Michel Vounatsos, chief executive officer at Biogen, in a statement.2 “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 (NCT02484547) and ENGAGE (NCT02477800) clinical trials have been the subject of much debate after an initial futility analysis completed in March 20193 showed that the drug missed its primary end point. However, results of an additional analysis of the EMERGE dataset announced in October 20194 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.
READ MORE: Eisai Stays the Course on Amyloid Despite Setbacks
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; P = .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 (NCT04241068) 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.
“The protocol of the re-dosing study that aims at offering access to aducanumab to all eligible patients who were actively enrolled in the aducanumab studies in March 2019 has been successfully submitted to the FDA,” Biogen said in a statement to NeurologyLive at the time. “We are now working with US trial sites to initiate this open-label clinical trial, which does not include a placebo-controlled arm.”
In a recent interview with NeurologyLive, Jeffrey Cummings, MD, ScD, director emeritus of the Lou Ruvo Center for Brain Health at Cleveland Clinic, and vice chair of the department of brain health at the University of Nevada, Las Vegas, shared insights from his annual review of the Alzheimer disease treatment pipeline, including thoughts on aducanumab. Watch below.
1. Biogen completes submission of biologics license application to FDA for aducanumab as a treatment for Alzheimer’s disease. News release. Biogen. July 8, 2020. Accessed July 8, 2020. https://www.globenewswire.com/news-release/2020/07/08/2059186/0/en/Biogen-Completes-Submission-of-Biologics-License-Application-to-FDA-for-Aducanumab-as-a-Treatment-for-Alzheimer-s-Disease.html
2. FDA accepts Biogen’s aducanumab biologics license application for Alzheimer's disease with priority review. News release. Biogen. August 7, 2020. Accessed August 7, 2020. https://www.globenewswire.com/news-release/2020/08/07/2074936/0/en/FDA-Accepts-Biogen-s-Aducanumab-Biologics-License-Application-for-Alzheimer-s-Disease-with-Priority-Review.html
3. Biogen and Eisai to discontinue phase 3 ENGAGE and EMERGE trials of aducanumab in Alzheimer’s disease. News release. Biogen. March 21, 2019. Accessed March 21, 2019. https://www.globenewswire.com/news-release/2019/03/21/1758398/0/en/Biogen-and-Eisai-to-Discontinue-Phase-3-ENGAGE-and-EMERGE-Trials-of-aducanumab-in-Alzheimer-s-Disease.html
4. Biogen plans regulatory filing for aducanumab in Alzheimer’s disease based on new analysis of larger dataset from phase 3 studies. News release. Biogen and Eisai. October 22, 2019. Accessed October 22, 2019. https://www.biospace.com/article/releases/biogen-plans-regulatory-filing-for-aducanumab-in-alzheimer-s-disease-based-on-new-analysis-of-larger-dataset-from-phase-3-studies/