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Alzheimer's Disease

The Aducanumab Approval

As the world knows, the FDA approved Biogen’s anti-amyloid antibody today, surely the first marketed drug whose Phase III trial was stopped for futility. I think this is one of the worst FDA decisions I have ever seen, because – like the advisory committee that reviewed the application, and like the FDA’s own statisticians – I don’t believe that Biogen really demonstrated efficacy. No problem apparently. The agency seems to have approved it based on its demonstrated ability to clear beta-amyloid, and is asking Biogen to run a confirmatory trial to show efficacy.

They will be absolutely overjoyed to do that, of course, because the whole time that’s going, they will be selling the first drug that (in theory) targets the etiology of Alzheimer’s. The backed-up demand is going to be gigantic, and Biogen is going to make enormous amounts of money. They have nine years, as it turns out, to get this trial done, and I feel safe in predicting that it’s going to take alllll niiiiine loooong sloooow years to get this done. Why shouldn’t it? The company certainly showed no interest whatsoever, not even a twitch, in running a confirmatory trial before this, so why should they hop to running one while the drug is selling? I continue to think that odds are quite good, and certainly unacceptably so for Biogen, that the drug will turn out in the end to have no real effect on Alzheimer’s patients at all. I’ve been dreading a decision like this for a long time.

So the FDA has, for expediency’s sake, bought into the amyloid hypothesis although every single attempt to translate that into a beneficial clinical effect has failed. I really, really don’t like the precedent that this sets: what doesn’t get approved, now? I suppose only things that definitely cause harm, because otherwise why not just ask for the same deal that Biogen got, and go out and prove efficacy while you turn a profit? I know that this is just the libertarian turn that many people have wished for, but I’m still not sanguine about it. I’m going to quote myself, because my opinion hasn’t changed a bit:

What would be so bad about moving to an “efficacy not required” regulatory regime? I think that it’s a flight from scientific evidence, which is the only thing we’ve got. Otherwise, everything starts to look like the “dietary supplement” industry, and what a mess that is. Here, you drop the efficacy requirement and I’ll develop grape juice for Dread Disease X. Not just plain grape juice – grape juice concentrate capsules. Mechanism? It’s the bioflavanoids. Probably. I think that they’re antioxidants, among other things. Lots of things. I can show safety in the clinic, too, so you have to approve my grape juice gel caps: I have a mechanism by which they might work (you can’t prove I’m wrong, can you?), I can show they’re safe, and you’ve eliminated the requirement that I prove that they actually do anything useful. Off to market! The patients who unfortunately suffer from Dread Disease X will, I’m sure, pay a lot for something that might help them. Don’t they have a right to try my antioxidants? There’s nothing else like them on the market, you know.

Go ahead and laugh – I mean, yeah, I’m pretty amusing, but I don’t keep grinning as long as I might when this topic comes up. The aducanumab approval, to me, is just a tiny step off of the radio-ad “Not intended to treat, cure, or modify any disease” memory supplements. It’s true that those ads always have to work in the line about how “These statements have not been evaluated by the FDA“, and at least Biogen doesn’t have to say that. Their statements have indeed been evaluated by the FDA, and the FDA has decided to punt on all the important ones and just let Alzheimer’s patients, their families, their insurance companies, and the taxpayers (through Medicare and the VA) pay for it all while we figure it out somewhere around the year 2030 or so.

Here’s Matthew Herper at Stat, talking about that exact FDA rule-change problem, and here’s Damian Garde and Adam Feuerstein trying (perhaps in vain) to estimate just how much money Biogen could be reaping from all this. That’s partly because, as Andrew Joseph notes, the agency applied no restriction at all to what patients can get the drug. Steve Usdin is gloomy about this at BioCentury, and wonders if this is going to open the door to many more such approvals in neuroscience and beyond. Zach Brennan’s not happy at Endpoints, either, and neither is their Bioregnum column. In general, the more you know about drug development and drug approvals, the more likely it seems that this decision came as an unwelcome surprise. That probably goes for plenty of people inside the FDA, come to think of it.

This was disgraceful decision, and we’re all going to be dealing with the consequences of it for years to come.

115 comments on “The Aducanumab Approval”

  1. Daren Austin says:

    “I really, really don’t like the precedent that this sets: what doesn’t get approved, now?” Technically, I think Sarepta set the precedent, but I share the sentiment. Proof-of-Pharmacology based conditional approvals for safe-but-hard-to-prove potential medicines?

    1. Alan Goldhammer says:

      At the end of the nine years, can American taxpayers sue Biogen for Medicare fraud if efficacy is not shown?

  2. While I’m inclined to agree with you, Derek, the only counter I can think of is that the FDA knows about ALL sponsor’s data/results. I’m just guessing (hoping) that Biogen’s beta-amyloid clearing data is better that that of other drug candidates studied in man. Yes, I realize the the connection between beta-amyloid deposition and loss of memory and cognitive ability remains unclear. Think of it as the Infusion Center full-employment act.

    1. Patrick says:

      Ok, but did their advisory committee *not* know about it?

      I’ll just go ahead and say it:
      This drug doesn’t work. It doesn’t help with Alzheimer’s. We are *almost certain* of this. The trial was literally *halted for futility*.

      Jesus fuck.

      1. DrOcto says:

        Why continue a futile clinical trial when you can just get approved on the spot….

  3. LL says:

    The decision should have been deferred until a new trial either confirms or refutes an efficacy signal – not before. We will see if the FDA will be able to take it off the market again in case the post-approval committed trial turns out negative.

    There should be a detailed review on sponsors, lobbying groups etc. who were involved in pressuring the FDA. The scientific advisors to the FDA recommended 10:0 (with one abstinence) against approval.

    And the price tag in the US is supposedly 56 k USD / year.

  4. OnceAChemist says:

    The Addyi approval after two previous FDA rejections was another step on the same slippery slope. My impression was that the final approval was driven primarily by a massive lobbying effort and social media campaign.

  5. Petros says:

    It will be interesting to see what the EMA’s CHMP recommend when they review it later this year. past experience suggest that approval will not be recommended.

    1. Lambchops says:

      I wouldn’t be surprised if they didn’t recommend it – from what I’ve seen the EMA is more cagey with CNS approvals than the FDA. At the very least expect a much narrower patient population (contrast the labels for cannabidiol for epilepsy – where the EMA label requires taking cannabidiol in conjunction with clobazam).

      As I’ve mentioned on these blogs before, I think it’s crushingly inevitable that there will be pressure on the MHRA in the UK for quick approval so that Boris can trumpet the glories of Brexit and fast approvals compared to the EU (cost-effectiveness evaluation is of course another issue – but I’d still rather see the regulators hold up evidence standards).

  6. myma says:

    It will also be interesting if-when-how-where Medicare-Medicaid covers this. Its an infusion, so its not just the list price of the stuff itself (~$5k each once a month dosing), its also the infusion center outpatient cost too.

    I used the word “stuff” because the word “medicine” seemed inappropriate.

    1. JasonP says:

      This is a key point! Whether The Centers for Medicare-Medicaid approve Aduhelm for payment or not. They use a criteria of how paying for the treatment effects patient outcomes and I am sure the economics of such. After all widely used in research, the PET AB & Tau tracers are NOT approved. This could be key in the eventual profitability.

      1. Another Idiot says:

        Agreed.

        If Medicare doesn’t approve it then neither will insurance companies.

  7. Tom says:

    Derek, your grape juice analogy is not quite correct. As far as I know, grape juice doesn’t lead to Amyloid Imaging Related Abnormalities in 41% of treated patients, or brain oedema in 40% of APOE e4 carriers.

  8. Dr. Manhattan says:

    Not mentioned is the added fact that in addition to no statistically decent proof of efficacy, on the Safety side there were a significant number of cases of swelling in the brain. These caused patient confusion and sometimes falls. So, questionable efficacy data but a safety signal. There was a very good reason for the expert panel to recommend not approving the drug.

    And added to that is the cost for the molecule that would be primarily in older adults, and the burden placed on insurers such as Medicare. Are thousands of dollars per patient per year worth the expenditure if the trial results are suspect? How much additional cost from patients treated for the side effects?

    A few years back, my company put a highly effective compound into man, but that turned out to cause elevated liver enzymes. Stopped the trial immediately, as should be the case. We come a long way from that time, and not in a good direction.

  9. Kiss the Chemist says:

    If this turns out to be a turkey we will only know NINE YEARS FROM NOW?! How the hell do we get the genie back in the bottle, potentially with other “me-too” antibodies on the market, and patients who want to keep being treated (based largely on false hope)?

    1. Lambchops says:

      Not to mention the opportunity costs. The research money inevitably splurged on “me-too” antibodies could potentially be better spent looking at other avenues of research.

      1. JasonP says:

        Oh come on! Research in drugs for AIDS didn’t stop just because the FDA fast tracked AZT.

        Plus it appears that with titration, ARIA can be managed. Many of the ARIA appear to self resolve with time as well

        The eventual “cure” for ALZ will end up being a cocktail or series of drugs, not one Silver Bullet. Clearing amyloid could be one part of the solution. Other avenues likely to include inflamation, Tau removal and microglial dysfunction.

        1. Patrick says:

          Oh come the f* on. We have approved a medication that does not help Alzheimer’s patients, which *we do not know how to do*. We *know how* to make amyloid clearing antibodies, and now companies are allowed to sell them.

          AZT ramped up research in antivirals because it showed we knew how to make medicines to help control AIDS (specifically antiretroviral small molecules). It likely sucked money out of competing approaches, which is fine, since the general approach of antiretroviral small molecules is a good way to fight HIV/AIDS and most of those other approaches were probably less good.

          Companies followed the money, doing the thing they knew how to do and were allowed to sell. Because the regulator insured this was beneficial to patients, we all benefited.

          THIS will drive up research in to medicines that help clear amyloid. Because we know how to do that. Patients be damned.

          Your statement that this is fine because it might help in some theoretical future world is pretty deeply useless in the context of current approval. It has no benefit NOW (it will in fact hurt people, it’s got some pretty bad side effects that should only be tolerated in the context of significant benefit), and it will not cease to exist if not approved.

          1. JasonP says:

            “Some researchers and advocacy groups have cheered the decision, while acknowledging that Aduhelm is far from a cure. “History has shown us that approvals of the first drug in a new category invigorates [sic] the field,” Maria Carrillo, chief science officer at the nonprofit Alzheimer’s Association, said in a statement.”

            https://www.sciencemag.org/news/2021/06/alzheimer-s-drug-approved-despite-doubts-about-effectiveness

        2. Emjeff says:

          The difference being, of course, that AZT actually worked, and they had the trials (note the plural) to show it.
          Also, they didn’t stop their trials for futility.

          Also AZT was used for many years and showed efficacy.

          Other than that, your analogy is perfect #sarcasm

          1. JasonP says:

            >>>The difference being, of course, that AZT actually worked, .<<<

            Oh gee. I think the LGBTQ community and scientists would disagree.

            " It is concluded that AZT, at the dosage prescribed as an anti-HIV drug, is highly toxic to human cells. "

            https://pubmed.ncbi.nlm.nih.gov/7744255/

            Plus variants emerged that were resistant to AZT.

            Oh and there is the "small" problem of SIDE EFFECTS! Hmmm, would I rather have some minor, transient brain swelling or "life threatening toxic effects "?

            My point was that research is NOT going to be inhibited just because one drug was approved.

            But if you wish, I like wet shoes….. (sigh)

        3. tommysdad says:

          JasonP: you’re not understanding the argument, which is a perfectly valid and concerning issue. This approval will spur the “investment” of millions & millions of dollars into making new versions of a drug THAT DOES NOT WORK. Those millions are being invested solely to reap the benefit of sales with no hope of improving the lives of patients. Those millions could/should be invested in other areas of research where they may actually move the needle on improving the lives of patients. So, yes, this approval will have the net effect of slowly the discovery of drugs that, you know, actually do something for patients other than give them (false) “hope”.

          1. JasonP says:

            @ tommysdad. Sounds like you have wandered off into conspiracy theory territory?

            If you want to keep tabs on ALZ research read here regularly.
            https://www.alzforum.org/

            Budgets of the NIH etc have been increasing and there is a TONNE of basic research on all levels. No shortage of research or papers out there. Takes too long to shift gears in this field considering the length of time it takes to get a CT approved and recruited. Then the time to run the trail, analyze the data and prepare a paper of the results. So can’t see this approval doing anything more than some companies attempting to use the “accelerated approval mechanism.”

            Plus the drug companies keep spending money on a “silver bullet” because the risk-reward ratio is pretty darn high. A successful ALZ drug is a multi-billion dollar cash cow and if they think they have a good shot at it, they’ll spend the money.

            There are already several AB antibody “drugs” out there. Eli Lilly is in a P3. What about 4 others have washed out? Might be something to do with the learning curve of what species of AB: soluble or aggregated, oligimers and what part of the AB the antibody attaches to. So no credible scientist or company is going to try a “me to” version in hopes of shody approval. They will still have to run the clinical trials, etc.

            So I can’t see any deleterious effects of this approval on what gets funded or doesn’t. Scientists are just shaking their heads and keeping their noses in their research.

  10. Radioactive Man says:

    All the other companies that successfully developed anti-amyloid drugs then discontinued them for lack of efficacy must be kicking themselves to realise they were approvable all along.

    1. Anonymous says:

      Or are they jumping for joy that Biogen is the one at the vanguard paying to set this precedent in money spent on lobbying and the (I hope, probably in futility) eventual backlash from the public over what is an unsafe drug that doesn’t do anything to help patients? Biogen opened the door, the rest can decide whether they want to walk through.

      1. Radioactive Man says:

        It makes me wonder, could they just simply dust off their old phase 3 results and go straight to applying for approval without even doing any more clinical studies? If those results are comparable to aducanumab, why not?

        1. Anonymous says:

          That was actually my unwritten implication in that comment, I should have said so explicitly. I imagine there’s a bit of red tape to revive a drug from a “failed” clinical trial and then submit an NDA, but when you see billions over the horizon for that therapy, how thick is that red tape anyway?

      2. Radioactive Man says:

        In fact thinking about it fast-tracking an anti-amyloid small molecule could actually be quite desirable (under the circumstances), because then at least we might be talking about a $5K placebo instead of a $56K one.

  11. Sok Puppette says:

    I’m one of those types who take the libertarian view, and I want to say that this is *not* what I’m looking for. This isn’t just people being allowed to evaluate evidence for themselves, or make their own decisions. FDA approval is an active statement from the government that the drug is safe and effective. The government has no basis to issue such a statement.

    What *should* be going on is that FDA approval should be advisory only. But it should still never be given for anything that doesn’t actually meet the stated criteria.

    … and, by the way, I don’t buy “proven safe” as a criterion and I don’t think anybody who’s thought about it has ever suggested that. Lots of things that clearly *are* beneficial are still not “safe”. In fact, the word “safe” is a magnet for sloppy thinking. It’s always a matter of trading off the probability and magnitude of the desired effect against the probability and magnitude of undesired ones.

    1. Dr. Mahnattan says:

      I agree that it’s true that many drugs are not *proven* safe, but can have an acceptable safety risk profile. The drug dosages can be managed to provide efficacy with a minimal safety risk. Effects such as CV arrythmias, liver & renal damage and other serious consequences are at one end of the spectrum. In the case of this drug, there were reports of brain swelling, in one report, 30% of the patients. Depending on how that plays out over time in larger populations, it may be consequential in some patients.

    2. Patrick says:

      Drug trials are hugely expensive, and unless you dispute that large, randomized, controlled trials are the only way to really determine safety and efficacy, then how do you propose they be paid for if approval if only advisory? The only reason they are run now is companies do not have a choice. You simply have to look back pre-FDA (or now, at the dietary supplement market, where almost nothing has much benefit, but it sells like crazy!) to see what they do when given a choice.

      And if you suggest that people will demand these trials even when they’re not required by law, I think you just need to look at the past year of pandemic to see how wrong that is. There are many, many people even in the medical establishment happy to “go with their gut” or run trials far too small to show what they’re claiming.

      1. Sok Puppette says:

        That is a genuine risk.

        A countervailing point, if not necessarily a knock-down one, is that insurance companies aren’t widely known for forking out tons of money for stuff that doesn’t work. In fact no large institutional funders tend to do that.

  12. Dan Elton says:

    A couple quick comments (much more could be said):

    — The FDA historically has been overly cautious, resulting in more Type I errors (failing to approve a good drug) than Type II errors. (see https://alo.mit.edu/wp-content/uploads/2015/08/FDA18b.pdf, published in SSRN). Type I errors are insidious because they fly under the radar. With a Type II error, the drug can be pulled off the market after follow up RCTs or Phase IV show it actually doesn’t work. (as a side note the Type I / Type II balance seems to depends on the type of drug – for instance in cancer drugs there seems to be an over-reliance on biomarker studies leading to what Vinnay Prasad calls “medical reversal” and too many Type II errors).

    — there isn’t any other treatment available, and AZ is a devastating condition. So it is arguably ethically cruel in this case to withhold a treatment that has some evidence to support it (even if it is weak evidence).

    — the FDA is requiring a post-market efficacy trial. This is great. The problem is the FDA (from what I’ve heard) sucks at enforcing these things. They need to enforce that it be done in a timely fashion and if the trial comes back showing no benefit they should pull the drug off the market. After all, selling something claiming it “works for indication X” when in fact it doesn’t work for X is fraud.

    — A rational and ethical approach to approvals should factor in unmet need and lower efficacy standards to get to market for drugs that have a chance at fulfilling an unmet need. The FDA should really have multiple tiers of approval or use adaptive licensing. At the top of these tiers would be the “gold standard” approval for safety+efficacy which means there is strong evidence for effectiveness. But there should be other levels too to get promising drugs to market faster and save lives and reduce costs. And there should be better post-market surveillance and recall of drugs where the evidence accumulates that they don’t work.

    1. MrXYZ says:

      These are interesting comments. The ‘tiers of approval’ idea is interesting but I am not sure how that would affect the industry since marketing approval is essentially a binary event (do you get to sell the product or not)? Obviously, enforcing post-marketing is key and unfortunately the government is much better at making rules than enforcing them (which requires giving agencies appropriate funding and authority for enforcement).

      Also, I am curious about your first statement. How do we know that the FDA has made more Type 1 errors than Type II errors? Is there a good review of NDAs/BLAs that have not been approved (as opposed to drugs that failed but never submitted an application). Could be an interesting read.

    2. metaphysician says:

      Put bluntly, neither doctors nor the fda should be in the business of providing “hope”. If you want hope, go to a church. Doctors, and the fda, should only be providing hard headed pragmatic fact. If there isn’t a treatment for your terrible illness, they should tell you that, not lie to you out of some misguided aversion to “cruelty”.

    3. John says:

      Do you know much time Biogen has to complete the trial ? 11 years.

      At 56K * 3 mil patients= $160 BILLION of sugar pill PLUS cerebral edema and death in quite a few!

      Also, when the confirmatory trial ends, the patent expires ! why the hell do they have to even do the trial? Just pull the drug off the market by 2031

    4. Brian says:

      Why exactly is it up to Biogen to run the confirmatory trial?

      That’s just how it works right now, but isn’t it an obvious flaw with an obvious solution? Get another government agency to do trials like that. NIH maybe. Make marketing approval for aducanab conditional on setting aside $X billion for that agency to use on the confirmation trial.

      That way we can get it done in a reasonable amount of time at least.

      For that matter, it seems like there’s a lot of example of non-pharma or off-patent treatments that could use a good clinical trial, where the normal industry profit motive doesn’t work. We should probably separate these functions.

      1. Emjeff says:

        The words “NIH” and “reasonable amount of time” should never be used in the same sentence. It would take NIH two years just to write the protocol.

      2. metaphysician says:

        “Why exactly is it up to Biogen to run the confirmatory trial?”

        Because they are the one wishing to sell it as a product which actually treats Alzheimers. They want to make the claim, they have the burden of proving that claim true.

        Or at least, that’s how it *should* work. Clearly things broke down here. . .

    5. Statistical pedant says:

      I think you have Type I and II errors mixed up there, Dan.

    6. DFrog says:

      So we know this is a highly unusual decision, and I keep asking myself–why?? I wonder if this happened because not enough Trump lackeys have been replaced? If there are enough remaining who have connections with Biogen or related entity, it would be in their interest to approve it despite hearty recommendations to the contrary.

  13. Erik says:

    Welcome back to 19th century medicine! A hundred years ago the American Medical Association got its act together and got rid of reams of quackery, condensing to only DOs and MDs. They still have the ultimate power in this system (in many ways – for example, state prosecutors rarely go after the rare doctors who harm patients before getting the okay from the state board of medical practice, or they allow the board to deal with it) but they’ve abrogated that power for so long by sticking their heads in the sand they’re basically shills for the exact same quackery they banded together to eliminate back then. Does it matter if the licensed physician treats with less-than-placebo (e.g. no effect yet causes harm such as a ~40% rate of brain swelling) or we simply allow dietary supplement makers to start making the same claims? Heck, at least those USP-manufactured supplements cause less harm… The physicians need to stop ignoring the damage that has happened _under their watch_.

    1. Erik says:

      Whoops, that’s 40% of APOE-e4 carriers, not all patients, my mistake. However, that group is going to be over-represented in the treatment groups.

  14. Running Comment says:

    Most BACE inhibitors and Abeta-clearing mAbs have shown effects on Abeta, sometimes dramatically so; in the absence of clinical benefit, however, the sponsors of these products correctly decided to pull the plug. Are we now going to see Merck, Lilly and Roche and Eisai et al. submitting their (equally) incomplete dossiers ? Why not ? The door is open…

    Re. the confirmatory trials, I believe I am quoting Derek from some time ago: “Real treatments work again when you test them again, and they continue to work when you test them under more controlled and more statistically powered conditions.”

  15. Metacelsus says:

    And to think that the FDA still hasn’t given full approval to COVID-19 vaccines based on “an abundance of caution”. Where was that caution now?

  16. anonnymous says:

    Bonanza for Biogen! Bag of crap for tax paying citizen of the US!

    1. ROBERT SALO says:

      At the end of 9 years Biogen will have pocketed potentially about 3,000 Billion dollars without having to do anything

  17. David says:

    A few predictions: 1) Biogen will take a long time to “negotiate” with FDA on the design of the confirmatory trial, effectively delaying the start. 2) The trial will have very restrictive Inclusion/Exclusion criteria, ensuring that there will be few patients available to enroll, 3) Biogen will focus on sites that use local IRBs, increasing study startup time, 4) the study sites will be exclusively academic medical centers, on the pretext that these generate the best quality data, but in reality for the reason that academic medical centers are notorious for slow recruitment, 5) Biogen’s marketing team will place significant resources to increase prescription use in the regions selected for the study, thereby competing for patients with study recruitment. 6) At the end of 9 years, the study will be just a little over half-recruited and Biogen will request a deferral on the timeline. 7) The availability of open-label treatment will lead to a high discontinuation rate in the trial, so the final results will be uninterpretable.

    1. tnr says:

      Good call.

    2. Jim Bonny says:

      David,

      Do you want a job?

      Great pay 😉

    3. Nobody important says:

      This confirmatory trial is already developed/ready for recruitment FYI. I don’t disagree with many of these posts but I wonder how many of you actually spend real clinical time with these patients and caregivers? If you don’t and are a researcher only please think twice before casting judgement.

  18. Radioactive Man says:

    $56,000/patient/year x 5.5million patients in the US = $308 BILLION/year.

    Even if only a small fraction of patients actually get it, this will easily be the most lucrative drug of all time.

    1. flem says:

      plus how many useless PET scans (@$7k) and MRI scans (@$3k) or lumbar punctures will be given. Can someone explain, given the equivocal results why the FDA would not insist on some relevant diagnostic criteria?
      I wonder how many free primary prevention clinics the government can open to treat underserved and under insured Americans with free blood pressure, blood cholesterol, and blood sugar (off patent) medications?
      I’d like to see a debate in Congress on this. Wonder where the GOP and DEMs will position themselves on this? thoughts

      1. tally ho says:

        The GOP will position themselves as they have done for the past 20 years, with their feet firmly planted in the mud and their heads squarely wedged between their hind quarters. The DEMs will cry foul about the GOP position. The GOP will wedge further. Congress is neither a scientific nor rational forum – it’s a political quagmire. It’s the last place to go for a debate to resolve this topic.

      2. Adam J Rosenberg says:

        The PET only applies if CMS and other will actually reimburse the PET drugs themselves after pass-through. The one silver lining in this is that they might actually fix the reimbursements there.

  19. Flask Monkey says:

    The FDA approved it but will the insurers pay for it?

    1. Ken says:

      That’s why I’m planning to sell it as a homeopathic preparation over-the-counter, ten bucks for a month’s supply. Any challenge by the FDA or Biogen will be countered by saying that the pills contain not one molecule of Aducanumab, so are not covered by FDA regs or Biogen patents. Any challenge on the grounds of efficacy will be met with a sneering laugh, and a press release on the subject of “giving hope to millions who can’t afford big pharma’s prices”.

      1. Alex says:

        Nice idea, but they’ll just sue you for trademark infringement.

    2. flem says:

      doesn’t medicare have too under the law?

  20. Hop Along says:

    I can’t believe that the FDA handed Biogen the keys to a multi-billion dollar franchise based on ambiguous data with no clear benefit. I hoped that the best outcome was the requirement for another confirmatory trial, correctly designed and powered but I just don’t understand this decision especially if you consider the broader usage label. If this is an emotional decision it really sets a poor precedent for the FDA and I can envision they will be sued by every Pharma Bro looking to get approval for some half baked compound.

    If I were in the legal profession I would already start drafting my new ad for daytime TV “Have you or a loved one been injured by Aducanumab?”

  21. Adam says:

    This actually makes Prevagen look like a pretty good option. Same placebo effect, a fraction of the cost, better safety profile.

    1. Dr. Manhattan says:

      I’m not sure about the Prevagen safety profile. I noticed in the television ads that they all seem to be moving in slow motion. Perhaps they are “thinking fast and slow” and that’s why they think it works? More time to ponder things if you are living in slow motion?

      Still puzzling how a Jellyfish protein, beside have a non-obvious pharmacological effect on cognition, gets through the stomach, across the intestinal tract, into the blood and through the blood brain barrier.

      1. Adam says:

        That’s assuming some sort of QA on Prevagen; it seems fairly likely the product on the shelf doesn’t contain any Jellyfish Nobel Prize protein. Maybe its just sugar, which distributes quite nicely across the BBB and has a number of positive effects.

      2. debinski says:

        I have always wondered what poor suckers fall for the jellyfish protein as some wonderful brain saving ingredient. But it does look pretty neat when they show the jellyfish swimming around all lit up – I guess the point is to imply it “lights up” the brain? There’s so much money wasted on supplements – but nothing that will compare with Aducanumab it sounds like.

  22. Sunyilo says:

    Just to add some background info how aducanumab was discovered: the antibody was derived from a screen by Neuroimmune who cloned B-cell products from Swiss individuals who grew to an old age without any symptoms of neurodegenerative diseases.

    What this approval tells us about our society in 21st century America? Go and monetize some insights into the conditions affecting many-many millions in our country and everywhere else instead of securing healthy living conditions to our population. Just as with the diabetes epidemic in the US.

    1. Patrick says:

      The Swiss individuals had genetic differences… The population level rate of Alzheimer’s is around 1.73% in Switzerland and around, a horribly worse and shocking …… 1.8% in the US. Since I couldn’t find a single shared source for both of those numbers, I think it’s safe to say they’re within the margin of error.

  23. metaphysician says:

    I am going to say something horrible: the best outcome we can hope for now is that aducanumab swiftly and unambiguously kills a large number of its recipients. The only way this won’t set a terrible precedent is if the people responsible, at both the fda and Biogen, are splashed with career-ending levels of blood. Aducanumab needs to be the next thalidomide.

    1. Emjeff says:

      The problem with that rather dangerous attitude is that, in correcting this mistake, FDA will undoubtedly place a very large additional burden on the pharmaceutical industry, which will wreak havoc on the companies actually doing real trials. Don’t think for a moment that the FDA will ever admit fault here – no one is government is ever held accountable for poor decisions. All the burden will be placed on the industry.

  24. Eric Kishel says:

    Could insurance companies just not cover this treatment, citing lack of efficacy? If it doesn’t improve the standard of living, or in other words does not offer any real value to the patient, then it certainly does not to insurance companies. They won’t be paying for a reduction in risk of larger expenses down the road, they’ll be paying something for nothing.

    If not them, what’s the next line of defense? Prescribing physicians? Pharmacists?

    Appreciate any insight that anyone can provide.

    1. Some idiot says:

      A couple of quick points:

      If my insurance company decided to pay for the treatment, then I would know that I need to switch insurance companies, because I don’t want to be with one which is wasting serious money on things which have no real benefit.

      As a poster on the pre-approval article pointed out, the flip side is not fun… Meaning that if insurance companies decide not to pay for it, then there will probably be lots of people desperate to find a treatment for loved ones, and who will then mortgage houses/whatever in order to pay for an ***approved*** drug… Which will also be a tragedy… Going broke due to a false hope…

  25. a says:

    Given the VAST moral hazards instantiated with this ridiculous approval, desperate times call for desperate measures.

    Are there any legal ways to get the FDA to rescind approval defacto or dejure? Lawsuit? Passing a Law? A Rule/Regulation?

    If we went down this route, I think theres a likelihood we’re in “there once was a lady who swallowed a fly” territory by stopping a FDA approval, but it’s too important to just shrug our shoulders and go, “eh”.

    1. Spring Texan says:

      You are absolutely right. Public Citizen wrote a letter to Xavier Becerra asking for the resignation of FDA officials and also suggesting: “You should direct the next Acting FDA Commissioner to consider whether the agency’s approval of Biogen’s BLA for aducanumab should be withdrawn.” The approval is an absolute disaster and any measures to possibly reverse it should be pursued.

  26. tnr says:

    The lack of FDA consistency between Aducanumab approval and the requirement that Amylyx run another Phase III study of its ALS compound is really troubling. Both were probably reviewed by the same Division at the FDA, so why require that Amylyx run another Phase III study when its small study hit on the primary endpoint AND overall survival???

    1. Dave says:

      The answer is in your post: Amylyx ran a small phase 2 study and the FDA wanted more data. Biogen ran 2 large phase 3 studies. The situations cannot be compared.

      1. tnr says:

        More data for what? The risk / benefit is pretty clear for AMX0035 even in the small Phase 2/3 trial. If all you want is a better picture of the long term side effects, that doesn’t require another placebo controlled trial. If the FDA is willing to give a conditional approval to Biogen, then they should be willing to give a conditional approval to Amylyx.

        in my opinion, the difference is that Biogen / Alzheimers patient advocacy groups exerted more effective pressure on the FDA than the Amylyx / ALS patient advocacy groups. Thats not what I want from the FDA in terms of drug approvals.

  27. DC Medchem says:

    President Biden has yet to nominate a permanent FDA Commissioner, unless I’ve missed a recent announcement. It will be interesting to see if this decision is discussed when confirmation hearings eventually take place.

  28. drsnowboard says:

    when wishful thinking allows an FDA drug approval, we’re screwed. Will make Valium, opioids, Skhreli look like mere blips.

  29. MikeC says:

    The most charitable excuse I can think of is that the top of the FDA was not ready to face the barrage from patient advocacy groups (weaponized by Biogen and Eli Lilly) that would have ensued after non-approval. Maybe they are hoping that another drug will be approved soon and then they can find an excuse to kill off aducanumab?

    The best case scenario now: an investigation or exposé torpedoes the approval before any prescriptions are infused.

    1. JasonP says:

      Speculative.

      I think some of the logic for approval could be found here:

      https://www.alzforum.org/news/research-news/aducanumab-approved-treat-alzheimers-disease

      >>>In the face of these pressures, the agency turned to its accelerated approval mechanism. Patrizia Cavazzoni, director of drug evaluation and research at the agency, noted that this pathway is “intended to provide earlier access to potentially valuable therapies for patients with serious diseases where there is an unmet need, and where there is an expectation of clinical benefit despite some residual uncertainty regarding that benefit.” Cavazzoni added that this regulatory option was not discussed at the advisory committee meeting. In a letter to the committee, the FDA’s Billy Dunn, who runs the neuroscience office, explained the agency’s reasoning, citing “substantial evidence that the drug reduces Aβ plaque, and that this reduction is reasonably likely to predict clinical benefit.”<<<<

    2. Spring Texan says:

      The first patient already received an infusion. I’m absolutely enraged by the comment below that AD is a devastating disease by this guy, as though that proved anything!! Given how infusion drugs are reimbursed, this eager proponent stands to make a lot of money, though. https://markets.businessinsider.com/news/stocks/first-patient-receives-biogen-s-alzheimer-s-drug-aduhelm-1030530079 Marc Archambault, 70 of Wakefield, received the infusion shortly before noon at Butler Hospital in Providence…”It’s transforming how we treat Alzheimer’s,” Dr. Stephen Salloway, director of the memory and aging program at Butler Hospital, said at a press conference. “For those of you who don’t know, it’s a devastating disease.”

  30. Till Bruckner says:

    Pharma occupies a really unusual niche in our economies. The prices paid are often kept secret in defiance of normal public procurement principles. Companies are sometimes given a decade to prove that a product they are already selling actually works. And when it then turns out that the product didn’t work, the company is not obliged to provide a refund.
    I know this all seems normal for people who have spent years inside the industry, but seen from the outside, these pharma exceptionalisms are remarkable. How did we get here, historically?

  31. Rich says:

    I’m figuring they’ll now run a massive astroturf campaign in countries like NZ with evidence based funding agencies (Pharmac in our case) in an effort to getbthis funded. Hopefully they’ll staunch it out.

    The only hope is that it becomes so blatant that it discredits these astroturf campaigns totally.

  32. Daniel Correia says:

    Hey, just out of personal curiosity, does anyone else know of a previous trial statistically similar – that is, with two effectively identical trials yielding moderate effect sizes in completely opposite directions?

    1. Patrick says:

      With signals this weak, signals that most observers have concluded are pure noise in both directions? Sure. Just look at a bunch of the HCQ trials. If you stare really, really hard at a trail of drug that doesn’t really do … anything … you’ll always see *something*. Randomness dictates the result does not lie perfectly at “0 effect”, it will always lie above or below that point. And if you slice thin enough, you’ll start to see things.

      The fact that the trials and measures of outcome go in opposite directions is *really* strong evidence we’re looking at noise. More or less irrefutable, in fact, which is why the FDA approved on the basis of amyloid clearance, because this way they can sleep at night by claiming they’re still following a rigorous standard.

      1. Patrick says:

        To clarify a bit:
        The evidence we’re looking at noise in cognitive change is not merely that results go in opposite directions, it’s that several different ones do – both trials and measures of outcomes – and all of the reported effect sizes are small.

    2. Emjeff says:

      No. I have very recent experience with two Phase 3 dose-ranging trials where, because of an unusually high placebo effect, the low dose did not reach statistical significance. The FDA did not approve this low dose, even though it did show an effect when you looked at the means, and we had efficacy data at that dose in a Phase 2 trial. We were turned down flat.

  33. Kanon says:

    I thought the point of running 2 phase 3 trials is to show significant results in BOTH trials, thus RAISING the bar, not EITHER one which LOWERS the bar compared to running just 1 trial. It’s like flipping a coin twice and claiming the coin is biased towards heads because heads showed up once! Jesus fuck indeed!

  34. Dave says:

    I’ll admit that I was not expecting an approval based on the clinical trial results but I’m quite happy the drug was approved. The FDA did not grant full approval though, only accelerated approval and these are meant for drugs that have been shown to meet surrogate endpoints that could reasonably be expected to produce clinical benefit to patients. Therefore if you think the amyloid hypothesis is reasonable then it follows that accelerated approval is reasonable. The FDA is requiring a confirmatory trial anyways and even if it takes 9 years to complete, that’s a short amount of time in Pharma.

    1. Patrick says:

      It could reasonably be expected to provide benefit under the amyloid hypothesis, but this isn’t the first drug to successfully clear amyloid, and there’s been no serious suggestion it’s particularly different in mechanism or efficacy in that task vs the earlier Lilly drug.

      So now you have to contend with the fact that these trials and the Lilly trials *all* failed. They failed. This set failed so badly they were stopped for futility on the basis of cognitive measures.

      So… why again do we think there’s going to be improvement? What’s the basis for it? This drug is *great* at clearing out amyloid. If that is disease altering, why didn’t it, well, alter the disease in trials?

      What’s the population or use case where it will do this? It has completely failed to do so, so far. That is a question that absolutely has to be answered to make a rational case for this drug.

      Remember it causes brain swelling and edema. This is a *dangerous* medication, that at a population level *will kill some people*, which would only ever be approved for a serious indication. It’s not “just take it, it’s safe”.

  35. Well, you probably know where I stand on this unconscionable decision. (If not, see linked file in handle; Science added the stupid title, not me and Adam.)
    Just dawned on me — not sure why it took >24 hours — that this approval “essentially returns us to the days before the 1962 Kefauver Harris Amendment…which first mandated data demonstrating drug efficacy.”
    Back to the days of Massengill, ca. 1938, and the comforting knowledge that if an FDA-approved drug doesn’t do anything useful, at least it won’t kill you.

  36. LEW ROMJE says:

    FDA’s dubious approval makes clear the agency interests to place patient safety behind big profits for Big Pharma & device industries. Perhaps the single worst red flag is the FDA’s mishandling of PEEK spinal cages that were designed & exclusively sold for use in the cervical spine, yet the agency allowed industry to label as “non-cervical” systems while not only concealing the actual risk profile, but providing entirely bogus instructions for use directing surgeons to implant the devices in the lower spine where they are “impossible to use for the labeled purpose.” [https://www.regulations.gov/comment/FDA-2021-N-0334-0005]. To add insult to injury, recent studies show the PEEK spinal implants failing exponentially over the gold standard, leading to costly, risky revision spine surgeries – all the while racking up big bucks for the device industry at the expense of patient suffering and lack of legally effective informed consent. FDA has betrayed the consumer by allowing industry to routinely conceal and omit material fact and safety information about the validated, verifiable design rational and risk/benefit. When we need a strong FDA more than ever, the agency charged with public safety appears opt for consumer to play Russian Roulette while stacking the deck on big profits.

  37. TallDave says:

    yeah was a bit shocked to see it, apparently showing plaque reduction was enough

    seems to be a lot we still don’t understand about this disease

    fortunately protein simulation is making progress, should help future research

    probably critical to extending longevity as Alzheimer’s seems to be one of those “eventually kills you if nothing else does” factors that place hard limits on human lifespan

  38. An Old Chemist says:

    Two doctors have resigned from a prestigious panel after FDA approved a controversial Alzheimer’s drug (June 9,21)

    https://www.msn.com/en-us/health/medical/two-doctors-have-resigned-from-a-prestigious-panel-after-fda-approved-a-controversial-alzheimer-s-drug/ar-AAKSmIj?ocid=msedgntp

    1. Helenus says:

      I wonder if any will resign at all after the EUA vaccine apocalypse? A defence that the future brings a collective and unthinkable, unimaginable catastrophe won’t wash. We know what viral evolution shall bestow in those protected by their vaccine induced antibodies. These scoundrels should be hung like at Nuremberg, but the scale of these crimes against humanity deserves a resurrection in punishment of biblical proportions. Hung, drawn, quartered and their remains pilloried in public. Lest we ever forget.
      Jabbing innocent children while the poor and invariably more coloured nations are left with less than 1% coverage of their most vulnerable and most cherished citizens. Karma’s coming for these monsters. The virus will kneel on your necks.

      1. francini says:

        Was waiting to see how long it would be before an anti-vax crackpot would show up to start spewing their tiresome, unfounded baloney. Ignore and move on.

        1. Trebich says:

          Why worry about the Alzheimer’s drug approval? It has better proof of efficacy than the holy and immensely useful masks and six feet distancing, shutting down half the country and loosing millions of jobs permanently. Eat what you have baked. This fraud is nothing new, all of you have happily taken part in this. Hurting millions was a cherry on top. Western culture is dying in front of us. Of course none of you have offspring, so it is back to “apre moi le deluge”.

  39. Jeff Weidner says:

    This reminds me of when the first statins got approved based only on cholesterol-lowering and years later generated the outcomes data. Since then we now know that the efficacy is more closely linked to the then-unknown anti-inflammatory effects. At least in that case they got lucky on the efficacy without knowing the mechanism. The problem here is that we now have decades of experience where apparently very well-validated mechanisms show biochemical efficacy without any change in the clinical endpoint. CETP is a recent example. We also have plenty of good drugs with clinical efficacy and no idea about their relevant molecular targets.

  40. Foggy Bottom says:

    This decision is brazenly corrupt. Something is rotten at the FDA.

  41. Artemisinin says:

    When we talk about phase 4 clinical trial, why the patients and the insurance need to pay for it? Shouldn’t it be from Biogen? Or at least Biogen should not make money from a CLINICAL TRIAL. It makes more sense that FDA mandates that a conditionally approved drug can only be sold at a set price to cover its cost.

  42. Your Face says:

    They should’ve approved it under EUA. Worked for COVID vaccines.

    1. No Nonsense says:

      While we’re at it, let’s classify old age as a disease and issue EUAs for all the drugs that target aging pathways.

  43. Bank says:

    At the Alzforum website, I was quite surprised to that this decision by the FDA was actually supported by some apparently well-informed and senior clinicians (see link in my name).

  44. Giorgio says:

    How does Aducanumab cross the BBB? can someone explain?

  45. JasonP says:

    The BBB isn’t some reinforced “fortress” with armed guards that keeps just about everything out. It is in effect selected Endothelial cells on the blood vessels in the brain. Part of the drug discovery process is figuring out if the targeted compound (at certain doses) reaches the intended target as well as being efficacious. In this case, I believe evidence of the antibody (or reaction resultants) in cerebral spinal fluid was used.

    Also there is increasing evidence that the BBB is “leaky” in ALZ situations and as one ages.

    As for the exact mechanisms of penetration, the experts here will have to lead you to appropriate articles and make any corrections to the above.

  46. dearieme says:

    Gentlemen, Ladies, you’ve missed the point. Somebody is desperate to get a drug they can give to Mr Biden. What further explanation is needed?

    1. Martyn says:

      Well, at least you got your username right.

  47. An Old Chemist says:

    Harvard’s Kesselheim quits AdComm over FDA’s Aduhelm approval (FierceBiotech, JUne 11, 2021):

    https://www.fiercebiotech.com/biotech/harvard-s-kesselheim-quits-adcomm-over-fda-s-aduhelm-approval

  48. Erik says:

    XKCD is quite apropos today: https://m.xkcd.com/2475/

  49. JenniferRM says:

    Derek, I love you and have learned SO MUCH about interpreting the practicalities of chemistry from reading your blog, but this feels to me like it is a step towards the FDA becoming even more a parody of itself as imagined by a libertarian.

    It does NOT seem to me like “just the libertarian turn that many people have wished for”.

    The problem with the FDA, under the theory that the FDA is structurally bad, is that instead of *doing science* (which creates a public good, and will be under supplied by the market) or regulating *fraud in medicine* (at the level of doctor/patient interactions and diagnosis/promise/outcome reporting systems) the FDA is just censoring the drug market based on backroom deals and p-hacking and whatever, to decide which pharma companies get a privileged “official market access patent” or not.

    The claim is that it was NEVER really about efficacy or safety and it was always about using backroom deals to decide who gets the profits for plausible potions that might not work, and might even be recalled for MARKET DISCOVERED safety problems.

    Under the libertarian vision, the FDA is one brick in a vast wall, generated via regulatory capture, that exists to prop up oligarchic profit centers by preventing competition in medicine. The FDA is not the only brick, by far.

    For example, if you get diagnosed with a disease, Medicare could disburse “probably enough for a minimally but realistically adequate treatment to prevent people from needing to beg on the internet” into a medical debit card with some monitoring on it. The Medicare folks should be cruising the internet looking for beggars, and asking them how and why medicare failed them, and if it is actually a scam, the scammy beggars should be thrown in jail for scamming people, and if it is not a scam then Medicare should debug the process and help for real.

    The goal would be to make it clearly and straightforwardly shameful to go begging like people do currently go begging to get gofundme donations, because The System would have clearly made such begging unnecessary. Medicare would be clean and honest government charity.

    Separately, there should be a distinct government run thing, which is an actual public health system that handled ALL AND ONLY the communicable diseases that either affect “the entire herd” (because herd immunity was NOT maintained), or effect almost no one (because the public health system is working properly). I’m talking HIV, covid, measles, etc.

    Public health is about communicable diseases. We have no such communicable disease management system in the US right now, so in a deep sense WE HAVE NO PUBLIC HEALTH SYSTEM in America. We’re like a third world country or something, in this way? Communicable diseases are intrinsically a public good, and any libertarian worthy of the name would admit that public goods are properly the domain of the government.

    These clinics should basically be free, and they should have offices in every port of entry, and the employees should work for the government and have the government authority to put people in some kind of “plague jail” if necessary. Wandering around knowingly infecting people with a communicable disease would be simply be a crime, and the doctors at these clinics would be like “cold cops”.

    (Also they should be doing pooled testing for diseases probably (because it is super cheap, and massively increases testing capacity), and also they should be sampling wastewater for pathogens. And so on. Protecting entire communities skillfully is possible, and would be a public good (which again: market are predicted to not provide adequately) but almost no one paid out of taxes is just DOING this in a clean and systematic and efficient and honest way.)

    Every time a very poor person gets a cold, they should go to a public health clinic like this. The treatment for communicable diseases would be free (treating one person for a cold in a proper way PREVENTS the cold from going exponential within the herd, and putting up with treatment like this shouldn’t cost people much at all… paying for the right to help others isn’t economically sane) and the treatment for anything else at such clinics would be: nothing.

    Some diseases are public (the communicable ones) and others are private (the incommunicable ones). Go to a private clinic for the private diseases. Boob jobs are private medicine. So is cancer. So is senile dementia. So is diabetes. For poor people, this is where medicare would kick in, and for the middle class and up this is where their private insurance would pay out MORE than medicare does (so they can afford better, faker, crazier, more experimental, more heroic, more luxurious treatment).

    In the private medical system, the patients (paying with medicare or not, it would be the same) could shop around among all doctors, and the doctors could be regulated like car mechanics who have to quote a price up front, and say what they will fix in writing, and get a signature agreeing to the planned fix. If the fine print says the thing won’t work… fine… that’s what a REAL “right to try” looks like. If an entrepreneur convinces a single doctor to sell a new thing to a single patient with extensive warnings in the fine print… great! We should trust doctors, right? Because they’re benevolent medical experts, right?

    Right now, car mechanics are more deserving of respect than doctors, because car mechanics do something clean and valuable and honorable, but after a reform like this, doctors might become more prestigious than car mechanics (which, honestly, is probably how it SHOULD be).

    Maybe medicare pays too little? It SHOULD be a little on the low side so that market movements can be used by the medicare folks to calibrate the payments. Then other insurance companies could sell “top ups” over and above the medicare, and the cash from the top-ups could hypothetically fund experimental treatments with concierge service and a money back guarantee if you catch MRSA in their facility… or whatever.

    A person could have many such insurance policies (purchased while they are still a kid? or before they start smoking? or whatever) preferably purchased long in advance of when they might realistically/predictably get the obvious diseases that they will probably get (so the risk pooling benefits actually work like they are supposed to on the tin). All the money would go into the same debit accounts that medicare pays into. They should stack, like annuities, or like life insurance policies.

    Right now having two health insurance policies can or would cause three times the headache because the current insurance scheme is basically just a system of privatized for-profit command-economy bureaucracies. The insurance companies would fight you and each other to try to force someone else to pay out for whatever treatment might have already happened (without any price quoted up front)… and all those paperwork gears would be grinding for no reason, and with no positive contribution to health outcomes.

    If you apply for direct diagnosis-for-cash insurance and the insurance quotes you a really high price for a certain payout on a certain diagnosis (because pre-existing conditions?) that should cause you to simply plan for the disease. Casinos throw people out for counting cards, and insurance companies are basically just casinos with a better story about how they hypothetically actually help some people manage their financial plans.

    If you have a pre-existing condition and no coverage, maybe look up what the medicare payout is, and lookup the Wikipedia article on the current best known way to use that amount of money to buy an adequate cure (or to find out that there is not yet a cure)?

    But isn’t that kinda insane? Wikipedia is a more plausibly trusted source than the FDA *right now* and it is run on donations, and mostly written and edited by volunteers. This is the opposite of how it should be, and to me it suggests that maybe the FDA would do more good if its employees spent more time buying products in the market and testing them in a lab, publishing the results, and then editing wikipedia to summarize the study… and less time choosing winners in the medical marketplace based on almost no data, and then analyzing the scarce data using committees and politics.

    The entire system I’ve proposed would put enormous pricing pressure on doctors. Plausibly, the percent of GDP spent on health would go way down. In my book: GOOD.

    The health per dollar of the US medical system is a disaster and a national disgrace. Every other nation gets more health for less cost, and many also get more health PERIOD. (My current “best of breed” health system is Singapore’s… Lee Kuan Yew was super smart.)

    (A bailout I would approve of if this reform happened: compensating doctors for their student loans, which they might not be able to repay after a reform like this, because they would probably make less money, because nearly all of their customers would switch from totally price insensitive to thoughtfully price conscious.)

    The FDA choosing a medical winner in the marketplace via a baroque bureaucratic monstrosity of a process, with no regard for efficacy, isn’t what a proper libertarian solution to medicine looks like… it is the final culmination of the obvious and obviously visible bureaucratic top-down farce that many people have quietly feared that the FDA always was.

    Repeal the Kefauver-Harris Amendment, drop GMP prior review of factory setups, switch to random testing of products for purity and dosing accuracy (with lots of testing on the first batch), rename the FDA (to acknowledge how shameful its previous iteration was), rehire the people who resigned from the FDA (because their resignation suggests they have integrity), fire anyone the rehired people insist would have to leave before they come back, and pivot the remaining organization over to market surveillance, the initiation of recalls, the shutting down of factories whose randomly sampled products are found to have impurities or false dosing claims, and hunting down doctors who might actually be committing a kind of fraud on their patients if they are promising efficacy and safety for drugs that actually only have technical/legal FDA approval.

    The FDA’s insanity becoming visible to everyone and then the FDA *continuing to exist beyond that point* is NOT what libertarians want.

    Libertarians want markets where markets are likely to work (because costs and benefits are local and owned) and actual public goods generated by an efficiently run state that knows when and how to stay in its lane and focus on the low cost provision of high quality public goods (like catching criminals, and enforcing contracts… which are also examples of public goods).

    The thing about the FDA is that it is at the top of the medical scam pyramid, and it provides a halo of “surely this is all working properly because of Science” to the rest of the scheme.

    But the scheme is BAD. It is uniquely bad in America. And the problem is not with the science of the system, the problem is with the political-economy of the system (or lack thereof).

    1. sPh says:

      “JenniferRM: Medicare would be clean and honest government charity.”

      There is no such thing as a “government charity”, certainly not in any Atlantic nation and to my knowledge in very few nations on the Earth. If a government institutes a program it becomes part of the commonweal. Medicare in the United States specifically was intended and designed as a contribution to ‘promote[ing] the general welfare’ by allowing all to contribute a reasonable amount through their working life and then obtain a decent retirement in the latter stages of life. This is in no way a “charity”; it is part of the fabric of our society and an inter-generational compact.

  50. SRP says:

    I suspect one reason for the approval is that the usual incentive balance for the FDA–to reject things because no bad headlines result from patients not getting things that might have helped them–was here neutralized by desperate and engaged (and probably supported by the vendor) patient groups. For example, one report said: :

    “The ADCS-ADL scale showed a robust 40% slowing of functional decline in the treatment group compared to the placebo group [7]. The Neuropsychiatric Inventory (NPI) that assesses an array of behavioral changes common in AD showed an 87% reduction from baseline scores in the high dose group of EMERGE [8]. There was a corresponding 84% reduction in caregiver distress.”

    Now, it’s entirely possible that Zoloft (for patient or caregiver) would also have reduced caregiver distress, but the pressure to give this thing a chance based on the lack of other good options was probably intense. Note that it was the FDA’s internal scientists who supported this drug.
    https://alzres.biomedcentral.com/articles/10.1186/s13195-021-00838-z

    1. Derek Lowe says:

      Only some of them – the FDA’s statisticians were strongly against it.

      1. SRP says:

        Sure, but the ball was carried by the civil-service staff scientists at FDA. This isn’t commissioners overriding staff.

  51. Barry says:

    Knocking plaques out of the brain without reducing dementia is a grave challenge to the beta-amyloid hypothesis. But there remain the “familial AD” cases in which know mutations to amyloid do correlate with dementia.
    Someone should run a new clinical with aducanumab in these patients only. It may turn out that “familial AD” is a false lead, sharing symptoms–but not etiology–with AD.

  52. Petros says:

    The Agenda for this week’s CHMP meeting shows that this is up for a (positive) opinion, i.e. an EMA recommendation of approval!

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