Biogen Alzheimer’s drug closer to FDA approval

This Longevity category product approval will bode well for our sector and will make institutional investors take note.

Biogen’s aducanumab, the first drug to actually slow the decline of Alzheimer’s disease, rather than just ameliorate the symptoms, would appear to be well on the way to FDA approval, despite some vociferous objections. FDA approval could come by March, making aducanumab the first new Alzheimer’s treatment for decades – but stormy seas still lie ahead.

Longevity.Technology: Aducanumab is demonstrating a Longevity all of its own after its comeback from the dead. Alzheimer’s has a large unmet medical need, and patient advocacy groups have argued that aducanumab, an antibody designed to remove amyloid plaques from the brain, should be accelerated through the FDA approval process. The FDA would appear to be listening, although some critics are not happy with that.

Shares of Biogen and its partner Eisai Co Ltd both jumped 40% after the FDA commented that evidence that the experimental Alzheimer’s disease drug is effective was “exceptionally persuasive”. There was a knock-on effect on shares of other Alzheimer’s drug developers, including Eli Lily and Co, which saw a 15% rise.

Aducanumab could gain FDA approval as early as March 2021 in what Mizuho Securities analyst Salim Syed described as: “almost a best-case scenario” for Biogen [1].

In a research note, Guggenheim analyst commented: “Briefing documents suggests a positive Advisory Committee vote, which bodes well for approval [2].”

“… a strongly positive study on multiple distinct and important clinical measures, robust to numerous sensitivity analyses, and supported by well-characterized biomarker data …”

The FDA says it “agrees that the results of study 302 are highly persuasive and the study is capable of providing the primary contribution to a demonstration of substantial evidence of the effectiveness of aducanumab. Study 302 is a strongly positive study on multiple distinct and important clinical measures, robust to numerous sensitivity analyses, and supported by well-characterized biomarker data … [there are] no findings from the exploration that represented evidence that aducanumab is not effective [3].”

Data from one of the aducanumab trials provides, say FDA staff: “the primary evidence of effectiveness as a robust and exceptionally persuasive study demonstrating” a clinically meaningful treatment effect [4]. Although a second large trial did not succeed the FDA were happy that the overall findings are positive.

It’s not all plain sailing, though; one statistical reviewer at the FDA said another study is needed to confirm whether aducanumab is effective. “There is no compelling substantial evidence of treatment effect or disease slowing,” FDA staffer Tristan Massie wrote in the review.

The idea of another study has not been welcomed by advocacy groups; Dr Howard Fillit, chief science officer at the Alzheimer’s Drug Discovery Foundation, said: “If a third trial is recommended then years could go by … while people aren’t granted access to the drug [6].”

However, an outside panel of experts threw cold water on burgeoning enthusiasm; during a virtual meeting that lasted seven hours on Friday, the panel concluded that a positive trial result could be considered to be as anomalous as a negative one. Although they agreed that the evidence that aducanumab is able to remove amyloid plaques is strong, they were unsure whether plaque clearance itself arrests cognitive decline. Out of the 11-person strong panel, no-one considered the evidence sufficient to warrant approval.

A lack of biomarkers and pathphysiology evidence downstream of amyloid plaque removal, could mean that perhaps we should consider beta-amyloid to be a less-than-preferable drug target in the future.