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Could someone please expand on the current outrage?

Article did say "The 11-member committee voted nearly unanimously in November that Biogen's drug should not be approved, citing inconclusive evidence that the drug was effective.", but was wondering why the some would think otherwise for the approval.




Derek Lowe has a recent article on the subject (https://blogs.sciencemag.org/pipeline/archives/2021/06/08/th...) that covers the issue in some detail by way of criticism.

In short, the medication does appear to reduce the beta-amyloid plaque buildup in the brains of patients with Alzheimer's. However, in the phase 3 study that plaque reduction did not appear to result in any clinical improvement in patients. The Phase 3 trial was "stopped for futility."

That's why the advisory panel could recommend rejection -- the drug did not appear to help patients. But equivalently, it did do the thing it set out to do, so that justified (ish?) the final approval.


It's worrisome because this sort of thinking - "We don't have proof that it treats the actual disease, but it does seem to treat with this thing that we think might be (but have yet to prove actually is) a cause of the disease, so let's forge ahead anyway." - has led to so many instructive case studies in purported cures that ended up being worse than the disease. It's a complete abdication of what should be basic scientific and medical principles to decide that an un- or ill-evaluated hypothesis is good and run with it, on no firmer ground than the fact that you happen to be quite fond of this particular hypothesis.


I don’t see what’s wrong with the FDA approving a drug only for specific niche proximate-cause X that currently has absolutely no reason to ever be prescribed, presuming it’s disallowed from being marketed as being “for” anything other than specific niche proximate-cause X. Maybe someday a problem will come along that can be solved by treating for specific niche proximate-cause X — and hey, then you’ve already got an approved drug to treat that problem. (For example, maybe in this case the drug could also happen to treat some novel prion disease, where the mechanism of that prion disease involves beta-amyloid buildup, such that this drug would actually stop that disease’s progression. Sort of the same way corticosterioids were already approved for other uses, but then happened to be able to be used in managing COVID, because the same mechanism they target — systemic inflammation — was being triggered by the disease.)

Of course, if the marketability restrictions truly worked the way I’m talking about, then the drug would have zero sales until that real-world problem matching its niche use-case came along. Which means there’d be no point in manufacturing it until then. But it’d be nice that it’d be “on the books” as being allowed to be produced and sold, such that it could be later rushed to market if the problem it solves was ever realized as a necessary problem to solve.


As someone else commented above - there is precendent to this, this is exactly how the HIV epidemic was approached. I was as upset about this decision as everyone else on this thread, then I read this[0] and now maybe not so much.

[0] https://forum.quartertothree.com/t/wtf-is-going-on-at-the-fd...


I'm impressed with the information and detailed discussions about this topic from a gaming forum...


This has historically been a challenge regarding understanding the mechanisms of Alzheimer's in the first place, let alone treating the disease.

We know the plaques and the memory dysfunction are correlated. But we don't know whether the plaques are build up of waste product from the mechanism that is destroying memory function or the cause of the memory function loss. If it's merely a waste product, clearing it out of the brain may not only have no effect on the memory loss, it could even accelerate it (if the chemistry of the process is such that build up of plaques interferes with whatever process damages memory). Destroying the plaques may be like picking a scab off a wound.

Biomedicine is hard; none of the systems operate in isolation and everything is intertwined.


It seems that the committee is an panel of outside advisors for the FDA.

The advisors advised that Aduhelm should not be approved because it only helps with a likely contributor to Alzheimer's, and it doesn't actually help with Alzheimer's.

The FDA ignored the panel and approved the drug anyways.

I wonder about the financial incentives and the corruption in the FDA. Every drug maker wants to be the first with an approved Alzheimer's drug; there's a ton of money to be made there.


> helps with a likely contributor to Alzheimer's

There is no evidence, and plenty of failed trials, to indicate that Amyloid plaque is a cause of Alzheimers.


I highly recommend the piece by Derek Lowe down thread, but the tldr is basically that researchers have believed amyloid plaques cause the symptoms of Alzheimer's and so the theory is that if you eliminate them, you can treat the disease. This drug gets rid of them. But the gold standard is whether or not the drug actually helps people, not whether it meets a technical definition of "working".

This is the drug equivalent of an engineer following a requirements document and saying to a product manager, "Hey, you said the form has to be submitted through the website. You can see here when I hit submit, it submits! The website doesn't save the data anywhere because that wasn't in the requirements".




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