FDA Reviewers Support Biogen’s Aducanumab
An FDA briefing document prepared for the 11/6 meeting of the Peripheral and Central Nervous System Drugs Advisory Committee speaks positively about Biogen’s Alzheimer’s drug aducanumab that the committee will discuss. An agency medical reviewer says one of the clinical studies submitted by Biogen “provides substantial evidence of effectiveness to support approval.” If the drug is approved, it will be the first new Alzheimer’s drug in nearly 20 years.
The briefing document acknowledges that aducanumab has had a checkered history. It notes that after promising clinical and biomarker data emerged from an early phase study, Biogen embarked on two trials of essentially identical design in 2015. A 2019 pre-specified interim analysis for futility led to the company terminating the studies and notifying FDA. However, later examination of individual study results, including additional data that had accrued during the time the futility analysis was being conducted, identified seemingly positive results in one of the two trials.
FDA says Biogen brought the results to the agency seeking confirmation of its analysis. “FDA recognized that additional work was necessary to achieve a maximum understanding of the results and established a collaborative plan for further rigorous analysis of the data,” the briefing paper says. “These analyses ultimately led to FDA advising the applicant that submission of a marketing application seeking approval of aducanumab was reasonable.”
The reviewers wrote that it appeared that a small number of patients with rapidly progressing Alzheimer’s might have skewed the clinical study and when their results were removed, the numbers favored the drug.
On the issue of safety, a frequent side effect of aducanumab has been a painful but manageable swelling of the brain called ARIA. Outside experts reportedly worried that the side effect might effectively unblind the study, informing patients that they had received the treatment and thus creating a bias in the study. The reviewers said an analysis of the data did not suggest that ARIA biased the trial.
Observers note that buried in the briefing document was a statement by an agency statistical reviewer that the one positive trial of aducanumab cannot overcome the negative one. “There is no compelling evidence of treatment effect or disease slowing and … another study is needed to confirm or deny the positive study and the negative study,” that reviewer wrote.
If approved, aducanumab would be the first drug to reduce cognitive decline in Alzheimer’s patients by targeting and eliminating clumps of a toxic protein called beta amyloid that are thought to destroy the brain. Observers say it would be a significant medical achievement.