14 ms·

The Aducanumab Approval

144 points by hprotagonist 5y ago

raverbashing 5y ago
This, and several other discussions remind me of this post in SSC https://slatestarcodex.com/2014/06/15/fish-now-by-prescription/ https://slatestarcodex.com/2014/06/15/fish-now-by-prescripti... (Though to be fair fish oil apparently has more evidence for its efficacy) Also the same for several purported treatments for Covid. Efficacy is less important than cost and potential profits.
Metacelsus 5y ago
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?
- CarelessExpert 5y ago
  If the FDA views its role as evaluating for harms only and not efficacy, then this isn't itself necessarily a contradiction. That doesn't change the fact that this approval is deeply disheartening and tells us the FDA is cool with any random product claims so long as they don't actively hurt people. But, hey, for all those folks who glory in the good ol' days when men were men and radium was a cure-all, the good news is at this rate we'll be back to snake oil and patent medicine in no time!
- adrianN 5y ago
  It is unlikely that this drug will be given to a comparable number of people as the vaccines. That makes tail risks a lot less important.
- CaliforniaKarl 5y ago
  I strongly recommend making Derek's "In The Pipeline" column a regular read, because he provides the information that answers your question. First, there are the number of people who would take the thing. Alzheimer's is terrible, but I think many more people would take a COVID-19 vaccine than have Alzheimer's. A drug that causes problems in 0.1% of people is treated differently when the population size is 29.8 million[0] people of advanced age vs. 7.8 billion people[1] of all ages. Second, the FDA has more than one advisory committee[2]. Which makes sense; I don't expect the world expert on CPAP and BiPAP machines to also be the world export on COVID-19 vaccines. [0]: https://en.wikipedia.org/wiki/Alzheimer's_disease#cite_note-GBD2015Pre-8 https://en.wikipedia.org/wiki/Alzheimer's_disease#cite_note-... [1]: https://www.worldometers.info/world-population/ https://www.worldometers.info/world-population/ [2]: https://www.fda.gov/advisory-committees https://www.fda.gov/advisory-committees
deeviant 5y ago
Coming soon: insurance companies refusing to cover this because efficacy has not been demonstrated and stories of impassioned family members fighting against evil insurance companies in order to cover "the medicine their love one desperately needs".
- HarryHirsch 5y ago
  It already happened in Britain over cancer medication: https://www.bbc.com/news/health-39711137 https://www.bbc.com/news/health-39711137 You'd predict that in a few years and after a few billions wasted regulators will wake up to the Phase IV results and withdraw approval.
  - pessimizer 5y ago
    The NHS still does homeopathy. They phased out most of it in 2017, but they still do it.
    - aliasEli 5y ago
      But i would expect that the cost of these medicines are quite a bit lower. After all water is pretty cheap. Most of them are just placebo's, but then again placebo's really do work.
- PragmaticPulp 5y ago
  This drug is primarily targeted at elderly populations, who are eligible for Medicare. The private insurance companies won’t be paying for this one. Taxpayers will.
  - borski 5y ago
    This is one of those comments I want to bookmark and come back to in a decade. :)
- zamalek 5y ago
  > impassioned family members Imagine how hopeful these families feel right now. I really hope Derek turns out wrong, but I know it's unlikely that he will.
tootie 5y ago
Good chuckle, but he's missing another tack to this. Saying it's purely based on safety and not efficacy makes it equivalent to the dietary supplement market is missing a key point. And that's the potential upside. Taking a moonshot on curing Alzheimers is far more worthy than taking a moonshot on curing varicose veins. As the Boomers start to hit their twilight years, we're going to have an absolute epidemic of Alzheimers patients and exactly zero chance of treating any of them with anything but palliatives. If Aducanumab has a 3% chance of success, then by all means we have to try. And if Biogen gets rich off of a flop, at least it will encourage more pharmas to get in on the action.
- jolux 5y ago
  They have failed to prove efficacy in a trial. Why believe it has a 3% chance of working? Do you think arbitrary chemicals have a 3% chance of curing some disease, even when it has yet to be shown? There’s absolutely no reason to believe this.
  - tootie 5y ago
    It's not a random drug. It's proven to reduce plaques. The phase 3 trials were inconclusive in proving that it improved patient outcomes which is certainly a bad sign but it's absolutely possible that future trials would show different results. I'm not saying the FDA is definitely right. I'm admittedly out of my depth on this topic. All I'm saying is this blog glossed over the severity of the problem they are trying to solve. Dementia is absolutely terrifying. My parents have already told me to euthanize them if it ever happens to them. I'd absolutely let them try this unproven therapy before doing that.
    - jcranmer 5y ago
      Derek Lowe's blog has an entire category for Alzheimer's that talks about the sordid history of drug candidates: https://blogs.sciencemag.org/pipeline/archives/category/alzheimers-disease https://blogs.sciencemag.org/pipeline/archives/category/alzh... Of particular note is that he, like most practitioners, is of the opinion that the record of unmitigated failure of amyloid blockers is that it means that the theory that reducing amyloid plaques improves outcomes should now be considered discredited. See, e.g., https://blogs.sciencemag.org/pipeline/archives/2019/01/30/another-alzheimers-antibody-fails-there-will-be-more https://blogs.sciencemag.org/pipeline/archives/2019/01/30/an... and https://blogs.sciencemag.org/pipeline/archives/2018/06/12/an-alzheimers-statement https://blogs.sciencemag.org/pipeline/archives/2018/06/12/an...
sparsely 5y ago
An absolutely shocking decision, which will have immense negative consequences for healthcare and healthcare costs far into the future. A license to turn false hope into profit margins and commissions for snake oil salesmen. List price is $56,000 per year if you're curious.
- nceqs3 5y ago
  List price doesn't matter in US healthcare FYI.
  - boreas 5y ago
    The fact that pharma has managed to obfuscate true prices is its own indictment of US healthcare. (edit) made my comment a bit less confrontational in tone
    - nceqs3 5y ago
      It's really the PBMs who have obfuscated the true prices. Check out the formulary incentive structure.
  - NoImmatureAdHom 5y ago
    Idk why the downvotes, this person is basically correct. Maybe downvotes because people find it distasteful? Lots of correct things are distasteful. Here's a discussion of the various ways of thinking about drug pricing in the U.S. (e.g., Average Wholesale Price (AWP). You can search using the acronyms if you're curious: https://www.rjhealth.com/2019/07/31/drug-pricing-101-reimbursement-rj-health-methodologies-drug-claims-code-level-unit-level-hcpcs-ndc/ https://www.rjhealth.com/2019/07/31/drug-pricing-101-reimbur...
Invictus0 5y ago
Is there any way that this decision could be overturned, and is that at all likely?
- yborg 5y ago
  Medicare could decide not to cover it, but that's unlikely. The story here is regulatory capture. The enormous and ever-growing profits of pharma give them equally enormous resources to throw at buying regulators and congressmen.
- aliasEli 5y ago
  Just have some patience. From TFA: > 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.
ProjectArcturis 5y ago
The FDA just allowed Biogen to suck hundreds of billions out of Medicare to pay for a drug that probably doesn't work.
- BurningFrog 5y ago
  The FDA only judges the medical evidence. That is complex enough. Adding pricing to it's concerns would make what is already a nightmare process even worse.
  - hn_throwaway_99 5y ago
    > Adding pricing to its concerns would make what is already a nightmare process even worse. TBH, I believe that is a huge root cause problem with our health care system. We need to stop pretending that money is infinite, and measure the cost against the benefit (in this case, little or none) when deciding whether Medicare/insurance companies should pay for a treatment. Perhaps this shouldn't be the responsibility of the FDA, but SOMEWHERE there should exist a process that says, "OK, this drug increases lifespan on average by 1 week, but costs $10,000 a month in treatment, sorry we're not going to cover it."
    - germinalphrase 5y ago
      Only a few short years ago, the eminently sensible idea of offering end of life planning (making a will, recording end of life medical desires) was demonized/weaponized as “death panels”. What you’re saying seems sensible, but my cynicism…
    - tomsto 5y ago
      This is how it works in the U.K. The MHRA decides which drugs are safe and effective and for which diagnoses. Then NICE decides which of those drugs are available on the public health system (NHS) by evaluating £/quality-adjusted life year. I don’t see why Medicare should be any different. If it’s not available on the public health system you can still pay for it yourself or via private insurance provided it’s licensed by the MHRA.
recursivedoubts 5y ago
all in all, just another brick in the wall watching social trust be destroyed on this scale in real time is both amazing and deeply disorienting
- germinalphrase 5y ago
  Attacking social trust is easy and profitable (across the political spectrum), but transitioning to a low trust society won’t make my life better.
  - recursivedoubts 5y ago
    in the short run in the long run, I suppose the feeling goes, we are all dead my children won't be though
bionhoward 5y ago
Biogen's stock performance yesterday was disturbing given the efficacy questions... This market feels whack. Anyone interested in a potentially more effective Alzheimer's AND Parkinson's drug might be interested in Annovis Bio: https://www.biospace.com/article/annovis-bio-shows-alzheimer-s-reversal-in-humans-in-phase-ii-study/ https://www.biospace.com/article/annovis-bio-shows-alzheimer... Given better results, it's a sign the plaque theory is wrong...
- jcranmer 5y ago
  Oh, Biogen's now guaranteed to make loads of money before the efficacy question comes back to bite them, because the FDA's approval greenlights them to sell it before the efficacy can be firmly resolved (i.e., they come out with their subsequent trial data which, if history is any indication, is pretty likely to say it doesn't work).
HPsquared 5y ago
So the drug has been shown to reduce these amyloid plaques, but the trials have not conclusively demonstrated any effect on patient outcomes. The author then claims it should be effectively banned for this reason. Why shouldn't someone be allowed to take it if they want to?
- jcranmer 5y ago
  There's a history of drugs that reduced amyloid plaques, perhaps with even better efficiency than aducanumab (I don't recall exact details) yet still failed to demonstrate any effect on patient outcomes. The commentary that the trials haven't "conclusively demonstrated any effect" is an understatement. Recall that one of the trials outright failed the endpoint, and the attempt to reconcile that with the other trial smells strongly of statistical hogwash. The advisory committee rejected it wholesale, with not a single vote in favor and only one vote not in disfavor (i.e., abstention).
  - jasonlaramburu 5y ago
    My understanding is that aducanumab has shown the greatest efficacy of any beta amyloid blocker (at reducing beta amyloid, with the least side effects. It definitely has side effects (brain swelling in 40%), but other Beta amyloid blockers have proven largely intolerable.
- vajrabum 5y ago
  Most of the patients this could be prescribed to are on Medicare. At $56k per patient and 5.5 million patients that's $308Billion. Oh and the drug causes edema in the brain in 40% of patients who are APOE e4 carriers which will be overrepresented in the patient population. That edema lead to confusion and patient falls. The scientific advisory board voted 10:0 with one abstention against approval. I'd just as soon not pay for something that doesn't work and in some cases causes harm.
  - shkkmo 5y ago
    I don't understand how a drug gets approved if the science board votes unanimously against it... who chose to override that decision?
PragmaticPulp 5y ago
If this was simply a matter of making the drug available for informed consumers willing and able to pay for it out of pocket, I wouldn't be as concerned. If we're going to have Medicare and private insurance companies pay $56K/year per patient for a drug that may not have positive effects that outweigh the risk of side effects, that's a major problem. Limiting access to experimental drugs is a difficult question. I know someone who has a different poorly-understood disease (not Alzheimer's, I'm being deliberately vague to avoid debates) who managed to get enrolled in a clinical trial for an experimental treatment. She responded fantastically well to the drug, as did a small number of other patients in the study. On average, however, the response to the drug was poor. She and several other responders have now found each other online and are trying multiple avenues to get back on the drug. They're getting desperate enough that they're pooling funds to order a custom synthesis from another country and have it analyzed for purity by a 3rd party lab. I'm terrified to think of the risks they're incurring, but they're so desperate to return to remission that they'd rather take the risks than continue to suffer. It must feel unthinkably unfair to be given a glimpse of remission, only to be forbidden to continue to buy the drug because it didn't work on a majority of patients. In their case, it's likely that the disease has multiple causative factors and the drug in question only treats one specific cause. Without stratifying trials by these yet to be determined different causes, it's difficult for trials to show efficacy on large populations. I wonder if Alzheimer's disease could be similar, in that certain subsets of patients respond to the drug but the average patient will not.
- shkkmo 5y ago
  I think we can improve access to experimental and unapproved drugs while still protecting consumers from malicious marketing of these drugs or sabotaging the current drug approval process.
  - epmaybe 5y ago
    How much more access can you possibly want on top of the previous FDA expanded access guidelines as well as the newer Right to Try Act?????
- adrianN 5y ago
sparsely 5y ago
I had a quick look at what various special interest "non profits" had to say about this: Alzheimer's Association -> very positive, basically an advert (https://www.alz.org/get-involved-now/new-day https://www.alz.org/get-involved-now/new-day). " A new type of Alzheimer’s treatment, aducanumab addresses the disease in a way that has never been done before. This therapy slows progression of the disease, rather than only addressing symptoms." Alzheimer's Foundation of America -> much more measured (https://alzfdn.org/alzheimers-foundation-of-america-statement-on-fda-approving-first-new-alzheimers-medication-in-nearly-20-years/ https://alzfdn.org/alzheimers-foundation-of-america-statemen...) "We are hopeful that it will improve the quality of life for individuals living with Alzheimer’s disease and their caregivers. Patient access and affordability to all of those in need is of significant importance." Alzheimer's Association transparency page claims that they received under $300k from Biogen in 2020 and that <2% of their revenue is from biotech - I feel like they are either selling themselves a bit too cheaply or being a bit dishonest. Their whole website feels weirdly corporate as well.
- pcrh 5y ago
  The article mentions the public pressure brought by these organisations. They may come to regret that pressure.
tunesmith 5y ago
Sorry, just a layman's medical question: If it's been shown to reduce plaque but not been shown to improve outcomes, is that positive evidence that it won't improve outcomes? Or is it more that noticing plaque reduction is fast while noticing outcome improvements would take a while? In other words, is this a case of "it's shown not to be efficacious, so wtf approval?" or is this more a case of "jury's out, so release it in the meantime"?
- ashwal 5y ago
  Important context is that all interventions that have assumed amyloid to be causal for Alzheimer's have failed to show material clinical improvement. So the bar is really much higher than "did remove plaque" and the prior should be this wasn't going to improve clinical response. The fact that it didn't and was still approved is a complete abdication of what the FDA preaches. It's rare to see a uniform response from those that report on drug dev. but it has been unequivocal - the FDA needs to get its shit together. I, personally, have little hope for that.
  - aliasEli 5y ago
    AFAIK there is no reliable non-invasive procedure to determine the amount of plaques in the brain. So it will be difficult to make hard statements about the effect of potential drugs on the plaques. Also we are not really very interested in the effect on plaques, we are interested in things like cognitive behavior which are a lot easier to measure.
- rossdavidh 5y ago
  I am no expert, but my understanding (referenced obliquely in the article) is that this is not the first drug to target reducing the amyloid beta plaque, that does not show positive results. This is raising the question of whether it's treating a side-effect of the disease, rather than actually treating the disease. In other words, it's not all that surprising anymore that a drug targeting the plaque, does not work well.
- jcranmer 5y ago
  > Or is it more that noticing plaque reduction is fast while noticing outcome improvements would take a while? This statement is true, but the trial will have gone on long enough to note whether or not both plaque reduction and outcome improvements happen, because plaque reduction isn't considered sufficient evidence for outcome improvement, despite some attempts to force the FDA otherwise. (Although I guess the FDA has kind of caved in at this point, given that it's conditionally approving this on the basis of plaque reduction despite seeing no outcome improvement.)
DOTIMES 5y ago
Given the studies showing higher rates of chronic infections in Alzheimer's patients (like herpes viruses and periodontal disease), why aren't there more trials like this: https://clinicaltrials.gov/ct2/show/NCT03282916 https://clinicaltrials.gov/ct2/show/NCT03282916 >Anti-viral therapy in Alzheimer's disease will investigate the efficacy of treating patients with mild Alzheimer's disease with the U.S.A marketed generic anti-viral drug Valtrex (valacyclovir, 500mg oral tablet). Valacyclovir, titrated to 4 grams per day, repurposed to treat Alzheimer's disease, will be compared to matching placebo in the treatment of 130 mild AD patients (65 valacyclovir, 65 placebo) who test positive for herpes simplex virus-1 (HSV1) or herpes simplex virus-2 (HSV2). The study will be a randomized, double-blind, 18-month Phase II proof of concept trial. I understand beta-amyloid is still the most likely cause of the disease, but given how lackluster the results of targeting beta-amyloid have been, why can't alternative hypotheses be investigated more fully?
- seasily 5y ago
  It's just a lucky coincidence that the industry colludes to not test generics (or falsify studies claiming they are ineffective, as was done with hydroxychlorquine) so they can continue to develop on-patent $56k per year drugs to sell.
azinman2 5y ago
Somewhat tangential question: there are all these new drugs with -mab and -ab suffixes. Why is that?
- xenophon 5y ago
  The -mab suffix means it's a "monoclonal antibody," or a lab-made protein that specifically targets a certain antigen (for example, an antigen found on a cancer cells).
- folli 5y ago
  See here: https://en.m.wikipedia.org/wiki/Nomenclature_of_monoclonal_antibodies https://en.m.wikipedia.org/wiki/Nomenclature_of_monoclonal_a...
  - azinman2 5y ago
    Wow that's really interesting. Good to see it's less random than these words seem to be! Thanks
- robbiep 5y ago
  As per the other commenter, but also they have a 10 year development pipeline and 10 years ago some major rockstars started hitting the market (ipilumimab, traztuzumab ) which are anti cancer ones but many others also). These were essentially the second generation of these drugs, the first gen sort of came out in the late 90s/early 2000s (ie Bevacizumab, infliximab ) and proved so versatile that they’ve spawned whole industries. The particular advantage is that a drug company can generate an antibody, clonally produce it, and demonstrate efficacy but no one else can claim the same efficacy because any other drug company is going to have an antibody that binds slightly differently and so has a different efficacy. (Ie so a generic here is called a bio similar antibody). There have even been bio similar that have had the opposite effect to the desired one (by for example acting as a receptor agonist rather than an antagonist)
mchusma 5y ago
There is no reason that "banning a drug" for everyone and "forcing medicare to pay for things" should be 1 thing. Should this be banned? Absolutely not. Should medicare be forced to pay for it? Also no. COVID vaccines were the same way. Should they have been banned early on? Absolutely not.
aliasEli 5y ago
Could you perhaps change the title? I have read several articles about it but I could not remember its name. It will probably get more views if you include "Alzheimer" in the title.

144 points by hprotagonist 5y ago

This, and several other discussions remind me of this post in SSC https://slatestarcodex.com/2014/06/15/fish-now-by-prescription/ https://slatestarcodex.com/2014/06/15/fish-now-by-prescripti... (Though to be fair fish oil apparently has more evidence for its efficacy) Also the same for several purported treatments for Covid. Efficacy is less important than cost and potential profits.

Metacelsus 5y ago

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?

CarelessExpert 5y ago
If the FDA views its role as evaluating for harms only and not efficacy, then this isn't itself necessarily a contradiction. That doesn't change the fact that this approval is deeply disheartening and tells us the FDA is cool with any random product claims so long as they don't actively hurt people. But, hey, for all those folks who glory in the good ol' days when men were men and radium was a cure-all, the good news is at this rate we'll be back to snake oil and patent medicine in no time!
adrianN 5y ago
It is unlikely that this drug will be given to a comparable number of people as the vaccines. That makes tail risks a lot less important.
CaliforniaKarl 5y ago
I strongly recommend making Derek's "In The Pipeline" column a regular read, because he provides the information that answers your question. First, there are the number of people who would take the thing. Alzheimer's is terrible, but I think many more people would take a COVID-19 vaccine than have Alzheimer's. A drug that causes problems in 0.1% of people is treated differently when the population size is 29.8 million[0] people of advanced age vs. 7.8 billion people[1] of all ages. Second, the FDA has more than one advisory committee[2]. Which makes sense; I don't expect the world expert on CPAP and BiPAP machines to also be the world export on COVID-19 vaccines. [0]: https://en.wikipedia.org/wiki/Alzheimer's_disease#cite_note-GBD2015Pre-8 https://en.wikipedia.org/wiki/Alzheimer's_disease#cite_note-... [1]: https://www.worldometers.info/world-population/ https://www.worldometers.info/world-population/ [2]: https://www.fda.gov/advisory-committees https://www.fda.gov/advisory-committees

deeviant 5y ago

Coming soon: insurance companies refusing to cover this because efficacy has not been demonstrated and stories of impassioned family members fighting against evil insurance companies in order to cover "the medicine their love one desperately needs".

HarryHirsch 5y ago
It already happened in Britain over cancer medication: https://www.bbc.com/news/health-39711137 https://www.bbc.com/news/health-39711137 You'd predict that in a few years and after a few billions wasted regulators will wake up to the Phase IV results and withdraw approval.
- pessimizer 5y ago
  The NHS still does homeopathy. They phased out most of it in 2017, but they still do it.
  - aliasEli 5y ago
    But i would expect that the cost of these medicines are quite a bit lower. After all water is pretty cheap. Most of them are just placebo's, but then again placebo's really do work.
PragmaticPulp 5y ago
This drug is primarily targeted at elderly populations, who are eligible for Medicare. The private insurance companies won’t be paying for this one. Taxpayers will.
- borski 5y ago
  This is one of those comments I want to bookmark and come back to in a decade. :)
zamalek 5y ago
> impassioned family members Imagine how hopeful these families feel right now. I really hope Derek turns out wrong, but I know it's unlikely that he will.

tootie 5y ago

Good chuckle, but he's missing another tack to this. Saying it's purely based on safety and not efficacy makes it equivalent to the dietary supplement market is missing a key point. And that's the potential upside. Taking a moonshot on curing Alzheimers is far more worthy than taking a moonshot on curing varicose veins. As the Boomers start to hit their twilight years, we're going to have an absolute epidemic of Alzheimers patients and exactly zero chance of treating any of them with anything but palliatives. If Aducanumab has a 3% chance of success, then by all means we have to try. And if Biogen gets rich off of a flop, at least it will encourage more pharmas to get in on the action.

jolux 5y ago
They have failed to prove efficacy in a trial. Why believe it has a 3% chance of working? Do you think arbitrary chemicals have a 3% chance of curing some disease, even when it has yet to be shown? There’s absolutely no reason to believe this.
- tootie 5y ago
  It's not a random drug. It's proven to reduce plaques. The phase 3 trials were inconclusive in proving that it improved patient outcomes which is certainly a bad sign but it's absolutely possible that future trials would show different results. I'm not saying the FDA is definitely right. I'm admittedly out of my depth on this topic. All I'm saying is this blog glossed over the severity of the problem they are trying to solve. Dementia is absolutely terrifying. My parents have already told me to euthanize them if it ever happens to them. I'd absolutely let them try this unproven therapy before doing that.
  - jcranmer 5y ago
    Derek Lowe's blog has an entire category for Alzheimer's that talks about the sordid history of drug candidates: https://blogs.sciencemag.org/pipeline/archives/category/alzheimers-disease https://blogs.sciencemag.org/pipeline/archives/category/alzh... Of particular note is that he, like most practitioners, is of the opinion that the record of unmitigated failure of amyloid blockers is that it means that the theory that reducing amyloid plaques improves outcomes should now be considered discredited. See, e.g., https://blogs.sciencemag.org/pipeline/archives/2019/01/30/another-alzheimers-antibody-fails-there-will-be-more https://blogs.sciencemag.org/pipeline/archives/2019/01/30/an... and https://blogs.sciencemag.org/pipeline/archives/2018/06/12/an-alzheimers-statement https://blogs.sciencemag.org/pipeline/archives/2018/06/12/an...

sparsely 5y ago

An absolutely shocking decision, which will have immense negative consequences for healthcare and healthcare costs far into the future. A license to turn false hope into profit margins and commissions for snake oil salesmen. List price is $56,000 per year if you're curious.

nceqs3 5y ago
List price doesn't matter in US healthcare FYI.
- boreas 5y ago
  The fact that pharma has managed to obfuscate true prices is its own indictment of US healthcare. (edit) made my comment a bit less confrontational in tone
  - nceqs3 5y ago
    It's really the PBMs who have obfuscated the true prices. Check out the formulary incentive structure.
- NoImmatureAdHom 5y ago
  Idk why the downvotes, this person is basically correct. Maybe downvotes because people find it distasteful? Lots of correct things are distasteful. Here's a discussion of the various ways of thinking about drug pricing in the U.S. (e.g., Average Wholesale Price (AWP). You can search using the acronyms if you're curious: https://www.rjhealth.com/2019/07/31/drug-pricing-101-reimbursement-rj-health-methodologies-drug-claims-code-level-unit-level-hcpcs-ndc/ https://www.rjhealth.com/2019/07/31/drug-pricing-101-reimbur...

Invictus0 5y ago

Is there any way that this decision could be overturned, and is that at all likely?

yborg 5y ago
Medicare could decide not to cover it, but that's unlikely. The story here is regulatory capture. The enormous and ever-growing profits of pharma give them equally enormous resources to throw at buying regulators and congressmen.
aliasEli 5y ago
Just have some patience. From TFA: > 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.

ProjectArcturis 5y ago

The FDA just allowed Biogen to suck hundreds of billions out of Medicare to pay for a drug that probably doesn't work.

BurningFrog 5y ago
The FDA only judges the medical evidence. That is complex enough. Adding pricing to it's concerns would make what is already a nightmare process even worse.
- hn_throwaway_99 5y ago
  > Adding pricing to its concerns would make what is already a nightmare process even worse. TBH, I believe that is a huge root cause problem with our health care system. We need to stop pretending that money is infinite, and measure the cost against the benefit (in this case, little or none) when deciding whether Medicare/insurance companies should pay for a treatment. Perhaps this shouldn't be the responsibility of the FDA, but SOMEWHERE there should exist a process that says, "OK, this drug increases lifespan on average by 1 week, but costs $10,000 a month in treatment, sorry we're not going to cover it."
  - germinalphrase 5y ago
    Only a few short years ago, the eminently sensible idea of offering end of life planning (making a will, recording end of life medical desires) was demonized/weaponized as “death panels”. What you’re saying seems sensible, but my cynicism…
  - tomsto 5y ago
    This is how it works in the U.K. The MHRA decides which drugs are safe and effective and for which diagnoses. Then NICE decides which of those drugs are available on the public health system (NHS) by evaluating £/quality-adjusted life year. I don’t see why Medicare should be any different. If it’s not available on the public health system you can still pay for it yourself or via private insurance provided it’s licensed by the MHRA.

recursivedoubts 5y ago

all in all, just another brick in the wall watching social trust be destroyed on this scale in real time is both amazing and deeply disorienting

germinalphrase 5y ago
Attacking social trust is easy and profitable (across the political spectrum), but transitioning to a low trust society won’t make my life better.
- recursivedoubts 5y ago
  in the short run in the long run, I suppose the feeling goes, we are all dead my children won't be though

bionhoward 5y ago

Biogen's stock performance yesterday was disturbing given the efficacy questions... This market feels whack. Anyone interested in a potentially more effective Alzheimer's AND Parkinson's drug might be interested in Annovis Bio: https://www.biospace.com/article/annovis-bio-shows-alzheimer-s-reversal-in-humans-in-phase-ii-study/ https://www.biospace.com/article/annovis-bio-shows-alzheimer... Given better results, it's a sign the plaque theory is wrong...

jcranmer 5y ago
Oh, Biogen's now guaranteed to make loads of money before the efficacy question comes back to bite them, because the FDA's approval greenlights them to sell it before the efficacy can be firmly resolved (i.e., they come out with their subsequent trial data which, if history is any indication, is pretty likely to say it doesn't work).

HPsquared 5y ago

So the drug has been shown to reduce these amyloid plaques, but the trials have not conclusively demonstrated any effect on patient outcomes. The author then claims it should be effectively banned for this reason. Why shouldn't someone be allowed to take it if they want to?

jcranmer 5y ago
There's a history of drugs that reduced amyloid plaques, perhaps with even better efficiency than aducanumab (I don't recall exact details) yet still failed to demonstrate any effect on patient outcomes. The commentary that the trials haven't "conclusively demonstrated any effect" is an understatement. Recall that one of the trials outright failed the endpoint, and the attempt to reconcile that with the other trial smells strongly of statistical hogwash. The advisory committee rejected it wholesale, with not a single vote in favor and only one vote not in disfavor (i.e., abstention).
- jasonlaramburu 5y ago
  My understanding is that aducanumab has shown the greatest efficacy of any beta amyloid blocker (at reducing beta amyloid, with the least side effects. It definitely has side effects (brain swelling in 40%), but other Beta amyloid blockers have proven largely intolerable.
vajrabum 5y ago
Most of the patients this could be prescribed to are on Medicare. At $56k per patient and 5.5 million patients that's $308Billion. Oh and the drug causes edema in the brain in 40% of patients who are APOE e4 carriers which will be overrepresented in the patient population. That edema lead to confusion and patient falls. The scientific advisory board voted 10:0 with one abstention against approval. I'd just as soon not pay for something that doesn't work and in some cases causes harm.
- shkkmo 5y ago
  I don't understand how a drug gets approved if the science board votes unanimously against it... who chose to override that decision?

PragmaticPulp 5y ago

If this was simply a matter of making the drug available for informed consumers willing and able to pay for it out of pocket, I wouldn't be as concerned. If we're going to have Medicare and private insurance companies pay $56K/year per patient for a drug that may not have positive effects that outweigh the risk of side effects, that's a major problem. Limiting access to experimental drugs is a difficult question. I know someone who has a different poorly-understood disease (not Alzheimer's, I'm being deliberately vague to avoid debates) who managed to get enrolled in a clinical trial for an experimental treatment. She responded fantastically well to the drug, as did a small number of other patients in the study. On average, however, the response to the drug was poor. She and several other responders have now found each other online and are trying multiple avenues to get back on the drug. They're getting desperate enough that they're pooling funds to order a custom synthesis from another country and have it analyzed for purity by a 3rd party lab. I'm terrified to think of the risks they're incurring, but they're so desperate to return to remission that they'd rather take the risks than continue to suffer. It must feel unthinkably unfair to be given a glimpse of remission, only to be forbidden to continue to buy the drug because it didn't work on a majority of patients. In their case, it's likely that the disease has multiple causative factors and the drug in question only treats one specific cause. Without stratifying trials by these yet to be determined different causes, it's difficult for trials to show efficacy on large populations. I wonder if Alzheimer's disease could be similar, in that certain subsets of patients respond to the drug but the average patient will not.

shkkmo 5y ago
I think we can improve access to experimental and unapproved drugs while still protecting consumers from malicious marketing of these drugs or sabotaging the current drug approval process.
- epmaybe 5y ago
  How much more access can you possibly want on top of the previous FDA expanded access guidelines as well as the newer Right to Try Act?????
adrianN 5y ago

sparsely 5y ago

I had a quick look at what various special interest "non profits" had to say about this: Alzheimer's Association -> very positive, basically an advert (https://www.alz.org/get-involved-now/new-day https://www.alz.org/get-involved-now/new-day). " A new type of Alzheimer’s treatment, aducanumab addresses the disease in a way that has never been done before. This therapy slows progression of the disease, rather than only addressing symptoms." Alzheimer's Foundation of America -> much more measured (https://alzfdn.org/alzheimers-foundation-of-america-statement-on-fda-approving-first-new-alzheimers-medication-in-nearly-20-years/ https://alzfdn.org/alzheimers-foundation-of-america-statemen...) "We are hopeful that it will improve the quality of life for individuals living with Alzheimer’s disease and their caregivers. Patient access and affordability to all of those in need is of significant importance." Alzheimer's Association transparency page claims that they received under $300k from Biogen in 2020 and that <2% of their revenue is from biotech - I feel like they are either selling themselves a bit too cheaply or being a bit dishonest. Their whole website feels weirdly corporate as well.

pcrh 5y ago
The article mentions the public pressure brought by these organisations. They may come to regret that pressure.

tunesmith 5y ago

Sorry, just a layman's medical question: If it's been shown to reduce plaque but not been shown to improve outcomes, is that positive evidence that it won't improve outcomes? Or is it more that noticing plaque reduction is fast while noticing outcome improvements would take a while? In other words, is this a case of "it's shown not to be efficacious, so wtf approval?" or is this more a case of "jury's out, so release it in the meantime"?

ashwal 5y ago
Important context is that all interventions that have assumed amyloid to be causal for Alzheimer's have failed to show material clinical improvement. So the bar is really much higher than "did remove plaque" and the prior should be this wasn't going to improve clinical response. The fact that it didn't and was still approved is a complete abdication of what the FDA preaches. It's rare to see a uniform response from those that report on drug dev. but it has been unequivocal - the FDA needs to get its shit together. I, personally, have little hope for that.
- aliasEli 5y ago
  AFAIK there is no reliable non-invasive procedure to determine the amount of plaques in the brain. So it will be difficult to make hard statements about the effect of potential drugs on the plaques. Also we are not really very interested in the effect on plaques, we are interested in things like cognitive behavior which are a lot easier to measure.
rossdavidh 5y ago
I am no expert, but my understanding (referenced obliquely in the article) is that this is not the first drug to target reducing the amyloid beta plaque, that does not show positive results. This is raising the question of whether it's treating a side-effect of the disease, rather than actually treating the disease. In other words, it's not all that surprising anymore that a drug targeting the plaque, does not work well.
jcranmer 5y ago
> Or is it more that noticing plaque reduction is fast while noticing outcome improvements would take a while? This statement is true, but the trial will have gone on long enough to note whether or not both plaque reduction and outcome improvements happen, because plaque reduction isn't considered sufficient evidence for outcome improvement, despite some attempts to force the FDA otherwise. (Although I guess the FDA has kind of caved in at this point, given that it's conditionally approving this on the basis of plaque reduction despite seeing no outcome improvement.)

DOTIMES 5y ago

Given the studies showing higher rates of chronic infections in Alzheimer's patients (like herpes viruses and periodontal disease), why aren't there more trials like this: https://clinicaltrials.gov/ct2/show/NCT03282916 https://clinicaltrials.gov/ct2/show/NCT03282916 >Anti-viral therapy in Alzheimer's disease will investigate the efficacy of treating patients with mild Alzheimer's disease with the U.S.A marketed generic anti-viral drug Valtrex (valacyclovir, 500mg oral tablet). Valacyclovir, titrated to 4 grams per day, repurposed to treat Alzheimer's disease, will be compared to matching placebo in the treatment of 130 mild AD patients (65 valacyclovir, 65 placebo) who test positive for herpes simplex virus-1 (HSV1) or herpes simplex virus-2 (HSV2). The study will be a randomized, double-blind, 18-month Phase II proof of concept trial. I understand beta-amyloid is still the most likely cause of the disease, but given how lackluster the results of targeting beta-amyloid have been, why can't alternative hypotheses be investigated more fully?

seasily 5y ago
It's just a lucky coincidence that the industry colludes to not test generics (or falsify studies claiming they are ineffective, as was done with hydroxychlorquine) so they can continue to develop on-patent $56k per year drugs to sell.

azinman2 5y ago

Somewhat tangential question: there are all these new drugs with -mab and -ab suffixes. Why is that?

xenophon 5y ago
The -mab suffix means it's a "monoclonal antibody," or a lab-made protein that specifically targets a certain antigen (for example, an antigen found on a cancer cells).
folli 5y ago
See here: https://en.m.wikipedia.org/wiki/Nomenclature_of_monoclonal_antibodies https://en.m.wikipedia.org/wiki/Nomenclature_of_monoclonal_a...
- azinman2 5y ago
  Wow that's really interesting. Good to see it's less random than these words seem to be! Thanks
robbiep 5y ago
As per the other commenter, but also they have a 10 year development pipeline and 10 years ago some major rockstars started hitting the market (ipilumimab, traztuzumab ) which are anti cancer ones but many others also). These were essentially the second generation of these drugs, the first gen sort of came out in the late 90s/early 2000s (ie Bevacizumab, infliximab ) and proved so versatile that they’ve spawned whole industries. The particular advantage is that a drug company can generate an antibody, clonally produce it, and demonstrate efficacy but no one else can claim the same efficacy because any other drug company is going to have an antibody that binds slightly differently and so has a different efficacy. (Ie so a generic here is called a bio similar antibody). There have even been bio similar that have had the opposite effect to the desired one (by for example acting as a receptor agonist rather than an antagonist)

mchusma 5y ago

There is no reason that "banning a drug" for everyone and "forcing medicare to pay for things" should be 1 thing. Should this be banned? Absolutely not. Should medicare be forced to pay for it? Also no. COVID vaccines were the same way. Should they have been banned early on? Absolutely not.

aliasEli 5y ago

Could you perhaps change the title? I have read several articles about it but I could not remember its name. It will probably get more views if you include "Alzheimer" in the title.