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D-Day for Aducanumab — What’s at stake: a BioCentury podcast

Jun 3, 2021 | 12:52 AM GMT

All eyes are on FDA as the PDUFA goal approaches for aducanumab, Biogen’s candidate for Alzheimer’s. On the latest BioCentury This Week – Special Edition, BioCentury’s editors discuss how the pending decision could have far-reaching ramifications for the development of therapies regulated by the Office of Neuroscience at FDA’s Center for Drug Evaluation and Research, and how the decision could affect the agency’s reputation.

To say that aducanumab from Biogen Inc. (NASDAQ:BIIB) has had a roller-coaster ride to reach this point would be an understatement, even in its most recent history. 

The anti-amyloid therapy failed two Phase III trials for futility in March 2019, only to have Biogen later report that one of the studies, EMERGE, actually met the primary cognitive endpoint, albeit with a large amount of imputed data, Executive Editor Selina Koch notes.

Then at a November 2020 meeting of the Peripheral and Central Nervous System Drugs Advisory Committee to discuss a BLA for the therapy, panel members voted 0-10 against the idea that EMERGE alone could reasonably be considered primary evidence of effectiveness of the mAb in light of supporting evidence from other studies.

FDA’s advisers not only roundly rebuffed aducanumab, they also lambasted the agency for bias in its presentation of the analyses. But there’s little doubt that FDA’s Division of Neurology 1 and Billy Dunn, acting director for the Office of Neuroscience, want to approve aducanumab, says Executive Editor Jeff Cranmer.

Washington Editor Steve Usdin addresses a misconception that aducanumab could receive a conditional approval, and discusses why it is crucial for FDA to be thorough and completely transparent in its explanation of its decision, whether positive or negative. 

Usdin suggests how the agency could achieve such transparency in an Editor’s Commentary, while an analysis by Koch compares aducanumab’s situation to past products that FDA approved after a negative advisory committee vote.

No disease-modifying therapies are approved to treat Alzheimer’s disease, a devastating and evenutally fatal condition, and the symptomatic therapies marketed for the condition provide only modest and often transient relief. Companies have been targeting β amyloid, widely considered the primary driver of the disease, for two decades to no avail.

Koch gives an overview of what’s involved in what FDA is weighing with its decision.

“The agency has to decide whether it’s going to side with the patient activists and doctors and scientists calling for approval of this therapy based on the very large unmet need, overlooking some of the deficits in the data package,” says Koch, “or whether it’s going to side with those folks who say, ‘look, the problems with the data are so glaring that if you approve this thing, it’s going to set the bar for evidence in Alzheimer’s disease so low that basically anything becomes approvable so long as a post hoc analysis suggests efficacy.’”

Usdin reminds that the Peripheral and Central Nervous System Drugs Advisory Committee is just that — a panel of advisers who are not making the eventual decision on a therapy.

“They’re often providing advice about medical and scientific issues that may not represent the totality of the reasons that FDA makes decisions,” Usdin says. “FDA is making a regulatory decision and its standards can be more comprehensive and go beyond the things that it’s actually asked for advice from the committee about.”

Usdin also says that FDA’s integrity and the confidence that the public and the companies the agency regulates are on the line, making it critical how FDA explains its decision

Many companies working in Alzheimer’s, some in amyloid, are closely watching the decision, Editor in Chief Simone Fishburn says, making it important that the agency make clear what companies will need to demonstrate to have their products approved. 

“There’s a lot at stake for patients, obviously, and for the industry,” Fishburn says.

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