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posted by Fnord666 on Friday June 11, @08:33AM   Printer-friendly [Skip to comment(s)]
from the I-quit! dept.

Member of FDA’s expert panel resigns over Alzheimer’s therapy 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."


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Amid Firestorm of Criticism, FDA Narrows Use of $56,000/Year Alzheimer’s Drug 32 comments

Amid firestorm of criticism, FDA narrows use of $56,000 Alzheimer's drug:

Less than five weeks after granting a highly controversial approval for the Alzheimer's drug Aduhelm, the Food and Drug Administration has updated its recommendation for who should receive the drug. The update narrows the recommended patient pool from all those with Alzheimer's disease to only those with mild forms of the disease.

The FDA's initial sweeping recommendation was a highly contentious aspect of the drug's approval, because it wasn't backed by any data. Aduhelm's developer, Biogen, had only included people with mild disease in its clinical trials. The numerous critics of the approval raised immediate questions as to why the drug would be open to all.

[...] Critics quickly called the approval "disgraceful" and "dangerous." Three members of the agency's advisory panel resigned in protest. Watchdog group Public Citizen called for the ouster of three top FDA officials.

Adding fuel to the fiery criticism is Biogen's decision to price Aduhelm at $56,000 for a year's supply. One analysis estimated that if the country's 5.8 million Medicare-eligible adults with Alzheimer's began taking Aduhelm, it could cost the federal insurance program $334.5 billion a year. In 2019, Medicare spent a total $37 billion for all drugs in the same category as Aduhelm, which is a doctor-administered drug. And the eye-popping cost estimate does not include additional, pricy brain scans and safety monitoring that taking the drug would require. While Aduhelm's efficacy is uncertain, the drug's known side effects include dangerous brain swelling and bleeding.

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  • (Score: 2) by PiMuNu on Friday June 11, @09:53AM (13 children)

    by PiMuNu (3823) on Friday June 11, @09:53AM (#1144205)

    Interested in why the drug doesn't work. Is it just that they didn't run the trial for long enough? Or is it that the Amyloid theory is wrong (correlation != causation etc)?

    • (Score: 0) by Anonymous Coward on Friday June 11, @10:32AM

      by Anonymous Coward on Friday June 11, @10:32AM (#1144208)

      From what I've read the main study didn't show correlation so they cherry picked a few cases from another group that sorta did if you squint.

    • (Score: 5, Interesting) by Samantha Wright on Friday June 11, @11:05AM (4 children)

      by Samantha Wright (4062) on Friday June 11, @11:05AM (#1144211)

      From TFA:

      While Aduhelm’s effect on cognition was debatable, both studies found that the drug was markedly effective at removing amyloid from patients’ brains. Over 78 weeks, patients who received the approved dose of Aduhelm saw roughly 30% reductions in amyloid, as measured by PET scan, compared to those on placebo. About 40% of clinical trial patients who got the approved dose of Aduhelm developed painful brain swelling.

      By "debatable" they mean that one of the studies showed no statistically significant impact, and the other showed an improvement of just 0.18%. It's definitively ineffective.

      My guess here is that they're simply too late. Most forms of dementia, including Alzheimer's, involve damage to a group of proteins called tau proteins. In Alzheimer's, it's possibly the case that amyloid causes the damage to the tau proteins before it forms plaques. Tau also seems to be a prion disease that self-propagates and messes up signal transduction in axons (the long part of the neuron that connects its output to the next nodes in the circuitry). The role of tau proteins has been known for a very long time (1976), but with Alzheimer's, big pharma was holding out hope that attacking the amyloid would help. As far as we know the brain functions normally when all amyloid beta is missing, though of course that's a very peak "Chesterton's fence [wikipedia.org]" sort of problem.

      I can't think of a good computing analogy that doesn't make it really messy, but basically: thing AB sometimes malfunctions, causing damage to everything, including itself and another thing, called thing T. Thing AB then piles up in big heaps. The drug removes the big heaps. Unfortunately, when thing T is damaged, it also damages itself, and thing M. When thing M is damaged, you have dementia. It is unclear whether thing T can be fixed. It is also unclear whether thing M can be fixed. Tragically, we can only detect Alzheimer's when people show signs of damage to thing M, and then confirm it by using lab tests to locate the big heaps of thing AB. If we don't find the big heaps, we just assume it's another form of dementia.

      It is possible that this drug could still be part of a treatment for Alzheimer's, but only in combination with drugs that fixes things T and M also.

      • (Score: 2) by Samantha Wright on Friday June 11, @11:08AM

        by Samantha Wright (4062) on Friday June 11, @11:08AM (#1144213)

        ("thing M" is hyperphosphorylation of microtubules in axons, which tau proteins are responsible for.)

      • (Score: 2) by PiMuNu on Friday June 11, @11:28AM (1 child)

        by PiMuNu (3823) on Friday June 11, @11:28AM (#1144218)

        Thanks. So it sort of sounds like indeed "correlation != causation" i.e. there is a cause - tau proteins mess up signal transduction - and amyloid is an effect; as well as dementia is an effect. Obviously not that simple and hard to disentangle cause and effect in very complicated system with poor instrumentation.

        Speaking as someone who has genetic predisposition to Alzheimer's (or at least I think so, I can't quite remember - gallows humour).

        • (Score: 1, Interesting) by Anonymous Coward on Friday June 11, @02:55PM

          by Anonymous Coward on Friday June 11, @02:55PM (#1144253)

          Amyloids are the lowest energy conformation for peptides. Without constant effort to clear them and fold proteins properly they will always form. That is why they are elevated in every diseased tissue known to humankind.

          If you are feeling very ill, you cant take out the trash and it accumulates in your house. Same thing.

          So, its not really correlatiom != causation. They have causation backwards.

          Of course at some point too much trash in the house starts to cause its own problems. But your mom coming over and cleaning the trash wont fix the root problem and may end up hiding how bad the problem is from your neighbors so they get sick too. That is why none of these amyloid removing drugs ever work, it is a huge boondoggle.

      • (Score: 0) by Anonymous Coward on Friday June 11, @04:26PM

        by Anonymous Coward on Friday June 11, @04:26PM (#1144281)

        I'm not an expert, but to confirm my understanding (and maybe make it more illustrative), maybe this would be an appropriate analogy?

        Somebody finds diamonds in ThirdWorldIstan (the AB malfunctions). Then lots of prospectors go flooding in and commence stripmining, leading to lots of pollution (AB piles up in big heaps). The pollution kills the herbivores in the local ecology (AB damages T), which devastates the food chain (T damages M). So we have a wrecked ecology (dementia).

        This drug would remove all the stripminers (remove the piles of AB), but doesn't actually fix the fundamental problem of the herbivores and the food chain being dead (T and M are still damaged), hence the ecology is still ruined (dementia still exists).

        Is that roughly what you were saying?

    • (Score: 1, Interesting) by Anonymous Coward on Friday June 11, @11:12AM

      by Anonymous Coward on Friday June 11, @11:12AM (#1144215)

      A very smart doctor/researcher in that field that I am slightly acquainted with is adamant that the amyloid plaques are the result of Alzheimer's, not the cause.
      He does say that an effective and non-damaging amyloid removal would provide some symptomatic relief, and delay the apparent progress of the disease, but it is not a cure.

    • (Score: 3, Interesting) by HiThere on Friday June 11, @01:19PM (2 children)

      by HiThere (866) on Friday June 11, @01:19PM (#1144237) Journal

      Probably the Amyloid theory is wrong. Every attempt based on it has been a dismal failure. The problem is that there *isn't* a decent theory of what causes it.

      One plausible theory that I've heard is that it's due to weakening of the blood/brain barrier. Something in the blood stream starts slipping into the brain. This is, IMNSHO, now more plausible than the Amyloid theory. The plausibility is, of course, largely, of course, because it hasn't really been checked out. After it's been investigated thoroughly it may turn out to be less plausible.

      --
      Javascript is what you use to allow unknown third parties to run software you have no idea about on your computer.
      • (Score: 0) by Anonymous Coward on Friday June 11, @03:07PM (1 child)

        by Anonymous Coward on Friday June 11, @03:07PM (#1144256)

        There is a decent theory that lead to beneficial drugs: the cholinergic hypothesis.

        For some reason this was abandoned in the 1980s in favor of the amyloid hypothesis, which became dogma even though that one has never lead to anything. Now, 35 years later, we get this farcical FDA approval.

        Medical research is becoming more pathetic every generation and it is accelerating.

        • (Score: 0) by Anonymous Coward on Friday June 11, @05:26PM

          by Anonymous Coward on Friday June 11, @05:26PM (#1144307)

          "Zzzzzzz... more research? Boring! Just give me something I can sell for fuck's sake. I can't sell you telling me things don't work. So just give me something, anything. I'll get it out there, you'll get a big fat bonus, and we'll all go home happy."

          Aren't MBAs great.

    • (Score: 2) by VLM on Friday June 11, @07:09PM

      by VLM (445) on Friday June 11, @07:09PM (#1144349)

      That science stuff doesn't matter any more. The problem is you set up a revolving door system where corporate execs take turns pretending to regulate the industry.

      Normally something like this should have been proposed by a major like Pfizer as one of their many blockbuster billion dollar drugs, but instead a relatively small company is offering it for only $50K/yr per victim of taxpayer medicare money.

      Essentially the wrong people are making money so the insider kingmaker types are PISSED off.

      Now if the regulators were made up of people trying to have a career at Biogen then the regulators would be happy to approve this billion dollar blockbuster. But instead they're Pfizer (and other) career minded people so they're pissed.

      In the end it'll be something like pfizer buys biogen for $20B instead of $10B and the price of the drug will be boosted up another $10K/yr per victim to pay for all the financial foolishness. Kinda like how endless mergers in the phone company arena changed the industry from $5 for a legacy POTS line to $50.

    • (Score: 1) by js290 on Friday June 11, @08:00PM

      by js290 (14148) on Friday June 11, @08:00PM (#1144370)
      Observation (amyloid plaque) vs Concept (causes Alzheimers, cum hoc fallacy)... off base concepts... make mgmt decisions in wrong direction [bit.ly]

      "Pharmaceutical companies are better at inventing diseases that match existing drugs, rather than inventing drugs to match existing diseases." - Nassim Nicholas Taleb in The Bed of Procrustes

      — Nassim Nicholas Taleb's Wisdom (@TalebWisdom) November 30, 2020 [twitter.com]

    • (Score: 1, Informative) by Anonymous Coward on Friday June 11, @11:36PM

      by Anonymous Coward on Friday June 11, @11:36PM (#1144411)

      There are a couple of issues here. First is that AD research has fundamental problem with noisy data. An individual with AD does not show slow and steady cognitive decline. They can jump up and down; they can stay steady and then show steep decline; they can improve apropos of nothing. This makes comparing groups notoriously difficult. There very well could be an improvement here, but is hidden in the noise, or their could be nothing and the trial showing great success was a type I error.

      Another issue is that AD might actually be a family of diseases with different but related causes. There are a number of genetic sources of early-onset AD, most of which directly alter the production of amyloid beta and its interactions. The cause of AD in those situations is the amyloid beta's effects, whether directly or indirectly. Another poster mentioned the cholinergic hypothesis, but that has problems because not everyone responds to that class of drugs, especially in genetically-caused individuals, and AD progression continues, which suggests that acetylcholine may be an indirect cause/effect of AD or the trigger of a subset of the disease proper. There is also inflammation, autoimmune, tau, metabolic, and other hypothesis, but most of them are in the form of a trigger that then causes numerous side effects, including amyloid beta effects, which then progress into full-blown AD. Together this all suggests that AD is multiple disease states that eventually converge onto what most people consider AD proper. The problem in telling them apart is, again, that AD research is notoriously noisy.

  • (Score: 5, Interesting) by looorg on Friday June 11, @12:31PM (7 children)

    by looorg (578) on Friday June 11, @12:31PM (#1144228)

    So pretty much non on the advisory panel though that this should be approved and yet it was approved? Clerical error? Enormous bribe? Someone didn't want their pension stock portfolio to tank?
    I guess the advisory expert panel might just be that and they have others that approved it but then it would be interesting why they reached such very different conclusions on or about the same data. Guess they have pushed the ball in to FDA court now that have better start to explain their side. After all sitting on an advisory board like this is no doubt somewhat prestigious and cushy and not something you would just give up cause of some minor disagreements.

    This should probably be edited and hooked to the previous line of stories, and once in the pipe, since this is apparently turning into a developing, or progressing, story over time.
    I noted there was even more in the queue and the number of people that have resigned is now up to three.
    https://soylentnews.org/article.pl?sid=21/06/09/1239206 [soylentnews.org]
    https://soylentnews.org/submit.pl?op=viewsub&subid=49218¬e=&title=Three+F.D.A.+Advisers+Resign+Over+Agency%E2%80%99s+Approval+of+Alzheimer%E2%80%99s+Drug [soylentnews.org]

    • (Score: 5, Informative) by HiThere on Friday June 11, @01:22PM (1 child)

      by HiThere (866) on Friday June 11, @01:22PM (#1144239) Journal
      --
      Javascript is what you use to allow unknown third parties to run software you have no idea about on your computer.
    • (Score: 5, Interesting) by Anonymous Coward on Friday June 11, @01:43PM (1 child)

      by Anonymous Coward on Friday June 11, @01:43PM (#1144240)

      Just plain old top down corruption. This [wikipedia.org] is the current head of the FDA. The same lady that, when previously acting as the head of the FDA's drug and evaluation research center also greenlit numerous drugs that fueled the opioid epidemic, also there rejecting lopsided advisory committee "suggestions" which, in turn, helped drive the resultant social devastation of the opioid epidemic. But hey, the pharmaceutical companies made a ton of money, and she got promoted. So who's laughing now?

      This drug stands to be billed at $56k/year/patient. It's going to make a lot of people very very rich, so who cares if it doesn't really work? Lol, I just looked at Biogen stock [yahoo.com]. It went, instantly, from $267 to $422 and is continuing to jam upward.

      • (Score: 3, Funny) by tangomargarine on Friday June 11, @03:12PM

        by tangomargarine (667) on Friday June 11, @03:12PM (#1144258)

        Just plain old top down corruption. This [Janet Woodcock] is the current head of the FDA. The same lady that, when previously acting as the head of the FDA's drug and evaluation research center also greenlit numerous drugs that fueled the opioid epidemic, also there rejecting lopsided advisory committee "suggestions" which, in turn, helped drive the resultant social devastation of the opioid epidemic. But hey, the pharmaceutical companies made a ton of money, and she got promoted.

        So what you're saying is, she's a dick?

        --
        "Is that really true?" "I just spent the last hour telling you to think for yourself! Didn't you hear anything I said?"
    • (Score: 2) by darkfeline on Friday June 11, @08:17PM (2 children)

      by darkfeline (1030) on Friday June 11, @08:17PM (#1144372) Homepage

      I'd guess that a lot of insanely rich old men are worried and are willing to try anything that might work. That would also explain the price tag.

      --
      Join the SDF Public Access UNIX System today!
      • (Score: 2) by looorg on Friday June 11, @08:59PM

        by looorg (578) on Friday June 11, @08:59PM (#1144389)

        I don't or wouldn't blame them. If I was in their shoes, had their resources and said affliction I would try anything to. There is probably no "cure" I wouldn't try if it came down to it.

        But it doesn't change that the price-tag is ludicrous and insane. Or that the FDA have apparently approved a drug that nobody appears to believe in and it seems very doubtful that it will actually work. At best it appears to be a 56k dollar (per year) placebo. Perhaps their massive influx of cash will do something good and fuel further research, but it doesn't really change how f*cked this appears to be. If anything it might just have fed the executive coke and hooker party for a few more years.

      • (Score: 0) by Anonymous Coward on Saturday June 12, @02:25PM

        by Anonymous Coward on Saturday June 12, @02:25PM (#1144572)

        If only... The same corruption that got this bill passed will get it covered by medicare. So everybody can have their $56,000 sugar-pill.

        And you'll be the one paying for it; directly through higher taxes to cover the 'healthcare costs of the needy and elderly' (doesn't that just make you feel all warm and cozy on the inside?), and indirectly through paying more for everything as we continue printing money to no end sending inflation up, up, and away.

  • (Score: 5, Interesting) by janrinok on Friday June 11, @02:04PM (3 children)

    by janrinok (52) Subscriber Badge on Friday June 11, @02:04PM (#1144245) Journal

    Three F.D.A. Advisers Resign Over Agency's Approval of Alzheimer's Drug [nytimes.com]:

    In a powerful statement of disagreement with the Food and Drug Administration's approval of Biogen's controversial Alzheimer's drug, three scientists have resigned from the independent committee that advised the agency on the treatment.

    "This might be the worst approval decision that the F.D.A. has made that I can remember," said Dr. Aaron Kesselheim, a professor of medicine at Harvard Medical School and Brigham and Women's Hospital, who submitted his resignation Thursday after six years on the committee.

    He said the agency's approval of the drug, aducanumab, which is being marketed as Aduhelm, a monthly intravenous infusion that Biogen has priced at $56,000 per year, was wrong "because of so many different factors, starting from the fact that there's no good evidence that the drug works."

    Two other members of the committee resigned earlier this week, expressing dismay at the approval of the drug despite the committee's overwhelming rejection [nytimes.com] of it after reviewing clinical trial data in November.

    The committee had found that the evidence did not convincingly show that Aduhelm could slow cognitive decline in people in the early stages of the disease — and that the drug could cause potentially serious side effects of brain swelling and brain bleeding. None of the 11 members of the committee considered the drug ready for approval: Ten voted against and one was uncertain.

    ...and...

    (...) Dr. David Knopman, a clinical neurologist at the Mayo Clinic, wrote in an email to F.D.A. officials informing them of his resignation from the advisory committee on Wednesday: "Biomarker justification for approval in the absence of consistent clinical benefit after 18 months of treatment is indefensible."

    Dr. Knopman, who had recused himself from the November meeting because he had served as a site principal investigator for one of the aducanumab trials, added that "the whole saga of the approval of aducanumab, culminating on Monday in the accelerated approval, made a mockery" of the advisory committee's role.

    --
    It's always my fault...
    • (Score: 0) by Anonymous Coward on Friday June 11, @03:24PM

      by Anonymous Coward on Friday June 11, @03:24PM (#1144261)

      > starting from the fact that there's no good evidence that the drug works."

      There was also ~30% chance of cerebral hemorrhage or effusion, ie leaky brain. Not to mention that none of the trial results were published besides in a powerpoint presentation, so who knows what more details would tell us.

    • (Score: 0) by Anonymous Coward on Friday June 11, @06:59PM

      by Anonymous Coward on Friday June 11, @06:59PM (#1144344)

      it's kind of strange that these docs didn't already know that the FDA is a big pharma legitimizing operation. gang of suited whores.

    • (Score: 1) by js290 on Friday June 11, @07:57PM

      by js290 (14148) on Friday June 11, @07:57PM (#1144369)

      We can have universal health by shutting down the USDA & FDA...
      What If There Was a Cure for Alzheimer’s Disease and No One Knew? by Mary Newport MD [coconutketones.com]

  • (Score: -1, Offtopic) by Anonymous Coward on Saturday June 12, @04:29PM

    by Anonymous Coward on Saturday June 12, @04:29PM (#1144612)

    Did anyone try bleach? If you inject it directly... in... the... is it the head? Or where's Alzheimers located. The head, right?

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