https://www.statnews.com/2021/...alzheimers-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. Billy 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.

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.”

“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.

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.)

It is important, Emerson said, for outside experts to have a voice in the decision-making process.

“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.”

Well that's comforting.

Follow the money trail.

quote:

Originally posted by FiveFiveSixFan:
“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.”

Well that's comforting.

For those who keep saying the vaccine isn't FDA approved....

FDA approval is largely a joke. I rest my case.

quote:

Originally posted by jcsabolt2:
Follow the money trail.

Biogen CEO says $56,000 annually for Alzheimer’s drug is ‘fair,’ promises not to hike price for at least 4 years

https://www.cnbc.com/2021/06/0...t-least-4-years.html

quote:

Originally posted by Flash-LB:
...

For those who keep saying the vaccine isn't FDA approved....

FDA approval is largely a joke. I rest my case.

FDA approval wasn't largely a joke not all that long ago. The number of drugs approved yearly now is pretty astounding. Unfortunately, many of those newly approved drugs will soon be the subject of late-night lawyer commercials which ask 'have you or someone you love suffered (insert malady here) from (insert name of once highly-touted drug here)? Call our law office at 1-800-GET-PAID and we'll fight to get you the money you're entitled to!'

quote:

Originally posted by wcb6092:
“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.”

Au contraire, Biogen, the drug's manufacturer, voted for it

quote:

Originally posted by Flash-LB:
For those who keep saying the vaccine isn't FDA approved....

FDA approval is largely a joke. I rest my case.

Not certain what "case" you think you're making, but I suspect your logic is faulty

Another disappointing drug heavily marketed for a high price. The UK often does not pay for these dementia drugs due to little if any efficacy.

I don't know.

On one hand, I can believe there was lobbying by Biogen.

On the other hand, a criticism of the US system was that we considerably lagged in trying cutting edge treatments that are allowed in other countries. For those patients and their families, waiting for the US to catch up was very frustrating. I see this as a step toward rectifying that. Wasn't this one of the things that Trump worked to improve?

On the other other hand, yeah, I can also see where a pay-off was implied to somebody somehwere.

^^^^^^^^^^^^
In recent years the United States has approved drugs BEFORE other countries. The United States used to be the laggard, ie Thalidomide that was never approved here but approved in Europe. It led to countless babies born without limbs.
Trump was pushing to get the price of drugs down. A good first step would be banning direct advertising to the public.

Biogen stock popped over 30% on the news, follow what money?

It's politics fellas. Science takes a backseat with the socialists and then they rebrand their bullshit, making it sound like things are efficacious when we all know the opposite. BTW just b/c a drug receives approval, doesn't mean it will be commercially successful. It's the image that counts to the Commies who are responsible for this latest daily non-sense.

quote:

Originally posted by FiveFiveSixFan:

FDA approval wasn't largely a joke not all that long ago. The number of drugs approved yearly now is pretty astounding. Unfortunately, many of those newly approved drugs will soon be the subject of late-night lawyer commercials which ask 'have you or someone you love suffered (insert malady here) from (insert name of once highly-touted drug here)? Call our law office at 1-800-GET-PAID and we'll fight to get you the money you're entitled to!'

Unlike most on this board, if not all on it, I was involved in FDA approvals for companies I worked for for around 9 years, and that's the basis of my saying it's a joke.

It's right up there with professional "certifications" that are actually attendance certificates.

I've sat on one of those advisory committees and they are strictly recommending bodies. How the FDA translates the recommendation into guidance or approval is anybody's guess. As stated, many times the outcome from the FDA may not be aligned with the committees recommendation at all. There's no insight into that process and it varies between the division performing the approvals/guidance. For example in the divisions I'm occasionally involved with - Center for Diagnostic and Radiological Health (CDRH) and Center for Biological Evaluation and Research (CBER)- they may have very different approval of outcomes on the same product for different indications (but physical interaction with the person is identical). i.e., CDRH will say it's safe and approve for in vitro diagnostic testing, but CBER will say its not safe for blood donor screening. Same test. Approval is based on use/risk.

And as usual (some exceptions noted for those dedicated to public service and betterment) most working for .gov aren't the sharpest tools in the shed. They've either flunked out of industry or gotten tired of the rigors required to maintain a for profit business and go get a 9 to 4 job with government benefits.

The FDA, CDC, and NIH are presently a joke in their current iterations.

RMD