How The FDA Does Business

by don - 2021-06-12 00:12:21 ( in education, research) [php version] rebuild

Of course, zlheimer's can be reversed with 20mg of lithium orotate a

day, so who cares?

Re: Medical Mafia

*Member of FDA's expert panel resigns over controversial Alzheimer's

therapy approval*

by Andrew Joseph

June 8, 2021

https://www.statnews.com/2021/06/08/...mers-approval/

"Following the Food and Drug Administration's polarizing

authorization of the Alzheimer's therapy Aduhelm on Monday, a member

of an agency advisory committee that recommended against the drug's

approval has resigned.

Neurologist Joel Perlmutter of Washington University in St. Louis, a

member of the FDA's expert panel for nervous system therapies, told

STAT in an email that he had quit the committee on Monday "due to

this ruling by the FDA without further discussion with our advisory

committee."

The advisory committee, which convened in November, couldn't have

been more openly skeptical of the drug, also known as aducanumab.

Ten of the 11 panelists found that there was not enough evidence to

show it could slow cognitive decline. The 11th voted "uncertain."

But the FDA still approved the treatment on Monday. On top of the

potentially massive implications for patients, clinicians, and

health care spending, the decision also raised questions about the

role of the advisory committees — and what it meant that the agency,

in its final adjudication, bucked the very panel it had convened.

"This isn't the first time when I was on a committee where the

committee voted one way and the FDA decided another," said

biostatistician Scott Emerson, a professor emeritus at the

University of Washington, who has served on many advisory committees

in different disease areas. "This was the first time that nobody

voted for approval of this drug — nobody — and they went against that."

The FDA does not have to follow its advisory committees'

recommendations — one study found the agency went against the

experts 21% of the time from 2008 to 2015 — but those overrulings

generally came when the votes were closer. The FDA often convenes

the panels when there is uncertainty around whether or how to

approve new products, and there are different "ad comms" for

different types of medications.

With Aduhelm, the story is also more complicated than the FDA just

rebuking the expert panel. The FDA granted the Biogen therapy what's

called an accelerated approval, based not on firm evidence the drug

slowed cognitive decline — which even the FDA acknowledged was not

clear — but on a "surrogate endpoint" that the therapy cleared toxic

protein plaques in patients' brains. In the FDA's view, that finding

"is reasonably likely to predict a clinical benefit to patients." It

also said Biogen would have to run another trial to confirm a

clinical benefit, though the results of that aren't due for nearly

another decade.

But during the advisory committee meeting last November, FDA

officials explicitly said they were not considering approving

aducanumab based on a surrogate endpoint. y Dunn, the director

of the FDA's Office of Neuroscience, made it clear: "We're not using

the amyloid as a surrogate for efficacy." That meant the panelists

were not asked to consider that possibility.

Related: Biogen isn't worried about backlash to 'bewildering' price

of Alzheimer's drug

So on Monday when the agency announced it had indeed given Aduhelm

the OK based on amyloid levels as a surrogate endpoint, it left

experts on the panel scratching their heads. Trials of other

amyloid-busting therapies have found that they didn't result in

clinical benefits.

What had happened, Dunn explained in a letter to the chair of the

panel Monday, was that after the panel hearing, there were "further

discussions" within the agency that "raised further consideration of

the accelerated approval pathway."

Related: Elation, pride, and a slew of questions: Clinical trial

participants reflect on their own complicated reactions to Aduhelm

approval

"We recognize that there has been tremendous public interest in

aducanumab and differing viewpoints on the extensive and complicated

data supporting the application for aducanumab," Dunn wrote. "Our

discussions leading up to the decision to grant an accelerated

approval for aducanumab considered a wide range of views, both

external and internal to FDA. We appreciate the comments from the

advisory committee members and can assure you that we listened

carefully and viewed the meeting proceedings as an important source

of input as we discussed the appropriate action."

To Aaron Kesselheim, an advisory committee member and the director

of Brigham and Women's Hospital's Program on Regulation,

Therapeutics, and Law, Aduhelm's approval didn't just set "a

dangerous precedent" for what kind of evidence an Alzheimer's

therapy would need to show to get the green light, "but even more

broadly for the idea that a company can turn around and at the last

minute seek [accelerated approval] when their primary clinical

endpoints in their trials don't reach the level needed for FDA

approval," he told STAT in an email.

Related: 'The price is bewildering': The cost of Biogen's

Alzheimer's drug may lead payers to erect roadblocks

It's no surprise that some members of the panel denounced the FDA's

approval, and not simply because of their votes. During the November

hearing, some of them criticized how the data was being discussed

and the evidence Biogen had submitted. Earlier this year, Emerson,

Kesselheim, and a third panelist published a paper in JAMA outlining

what they saw as the flaws of the therapy.

Still, Emerson, the biostatistician, said he would serve on another

advisory committee if asked. (The panels have some permanent

members, but for individual hearings, they invite "temporary

members," which included Emerson in the case of aducanumab.)

Trending Now: Third member of FDA expert committee resigns over

controversial Alzheimer's therapy decision

It is important, Emerson said, for outside experts to have a voice

in the decision-making process.

Matthew Herper contributed reporting. "

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