[HN Gopher] The Aducanumab Approval
       ___________________________________________________________________
        
       The Aducanumab Approval
        
       Author : hprotagonist
       Score  : 123 points
       Date   : 2021-06-08 12:51 UTC (10 hours ago)
        
 (HTM) web link (blogs.sciencemag.org)
 (TXT) w3m dump (blogs.sciencemag.org)
        
       | recursivedoubts wrote:
       | 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 wrote:
         | 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 wrote:
           | in the short run
           | 
           | in the long run, I suppose the feeling goes, we are all dead
           | 
           | my children won't be though
        
       | bionhoward wrote:
       | 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...
       | 
       | Given better results, it's a sign the plaque theory is wrong...
        
         | jcranmer wrote:
         | 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).
        
       | sparsely wrote:
       | 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 wrote:
         | List price doesn't matter in US healthcare FYI.
        
           | boreas wrote:
           | 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
        
       | HPsquared wrote:
       | 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?
        
         | vajrabum wrote:
         | 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 wrote:
           | I don't understand how a drug gets approved if the science
           | board votes unanimously against it... who chose to override
           | that decision?
        
             | nceqs3 wrote:
             | The FDA.
        
           | nceqs3 wrote:
           | MEDICARE DOESN'T PAY LIST PRICES!
        
         | shkkmo wrote:
         | There should be a step between banning and approval.
         | 
         | If you look at the history of hiv/aids drug approval it's
         | pretty clear that there is significant harm that can be done by
         | banning unapproved drugs.
         | 
         | At the same time, removing the requirement to show efficacy to
         | be approved is also quite obviously bad for the reasons
         | outlined in the article.
         | 
         | Why can't the company be allowed to provisionally sell the drug
         | with the warning that the FDA has evaluated the drug as
         | "unproven efficacy" until such a time as the follow up studies
         | are completed?
        
           | ceejayoz wrote:
           | We have such a thing. https://www.fda.gov/news-events/public-
           | health-focus/expanded...
        
             | shkkmo wrote:
             | My understanding is that while that helps in some cases,
             | the restrictions on its applicability leave a lot of people
             | high and dry.
        
           | EamonnMR wrote:
           | They could sell them as supplements but then they wouldn't be
           | legally able to claim efficacy or be billed as medicine. They
           | can't make nearly as much money without FDA approval.
        
         | gumby wrote:
         | > Why shouldn't someone be allowed to take it if they want to?
         | 
         | That's the standard libertarian argument and we have an actual
         | A/B experiment that shows what happens.
         | 
         | People used to be able to market any old thing (such as "snake
         | oil") to cure whatever they wanted to say. A regime was built
         | up over time (culminating in 1963) that you had to demonstrate
         | both safety and efficacy in order to sell a drug, and you could
         | only describe the drug in ways you had demonstrated (which
         | included manufacturing).
         | 
         | In 1994 Orrin Hatch (he of copyright maximization and senator
         | from a state with a lot of "natural" scammers") got a law
         | passed to say that anything "natural" was exempt from any FDA
         | rules and sellers could say whatever they want. And as a result
         | unlocked a huge snake oil business that preys on people when
         | they are feeling most vulnerable. Fortunately most of those
         | things are harmless nonsense but sadly not all.
         | 
         | If you decide there is no need to prove efficacy than nobody
         | would spend time on it. And thus drug had its trials halted
         | because nobody was being cured (not only do you not want to
         | spend money on them, but it's unethical to expose people to
         | side effects of a drug that doesn't help them.
         | 
         | The FDA is saying that even though it's unethical to do in a
         | trial it's OK to do in the market.
        
         | PragmaticPulp wrote:
         | > Why shouldn't someone be allowed to take it if they want to?
         | 
         | It's not entirely an issue of freedom. It's also about whether
         | or not taxpayers have to pay Medicare to provide it.
         | 
         | By some estimates, 1 in 9 people over the age of 65 have some
         | degree of Alzheimer's. The cost of the drug is estimated at
         | $56K per year.
         | 
         | If we, the taxpayers, are now on the hook to pay $56K/year for
         | up to 1 in 9 elderly people in the country for a drug that _may
         | not actually work_ and has some serious side effects, that 's
         | not good at all. Given the data we have, there's a significant
         | probability that we'd be paying $56K/year to make these
         | patients worse on average given the risk of serious side
         | effects of the drug with negligible appreciable upside. That's
         | a major problem.
         | 
         | It might be possible for Medicare to deny this drug due to lack
         | of efficacy, but that sounds like a political nightmare.
        
         | jcranmer wrote:
         | 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 wrote:
           | 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.
        
       | DOTIMES wrote:
       | 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
       | 
       | >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?
        
       | raverbashing wrote:
       | This, and several other discussions remind me of this post in SSC
       | 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.
        
       | mchusma wrote:
       | 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.
        
       | tootie wrote:
       | 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.
        
         | mekkkkkk wrote:
         | There's a huge market already saturated with moonshots like
         | this. It's called alternative medicine.
        
         | jcranmer wrote:
         | But the pharmaceutical companies _have_ tried several times to
         | get an Alzheimer 's drug that work. Being the first one to get
         | an approved drug is a license to print money to the tunes of
         | tens or hundreds of billions of dollars--enough to cover the
         | costs of development. The reason why we haven't had any yet is
         | because _they don 't work_.
         | 
         | Why should Biogen's probably-doesn't-work Alzheimer's drug get
         | a pass that the dozen or more attempts that showed similarly
         | bad results didn't get? Note in particular that the assessments
         | of everyone who looked at Biogen's statistical claims here is
         | that those claims are not substantiated by statistics.
        
         | jolux wrote:
         | 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 wrote:
           | 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.
        
             | wins32767 wrote:
             | Do you think you should be taxed so that everyone's parents
             | can try this unproven therapy for ~56k a person a year?
        
             | [deleted]
        
             | jcranmer wrote:
             | Derek Lowe's blog has an entire category for Alzheimer's
             | that talks about the sordid history of drug candidates: htt
             | ps://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/an... and https://blogs.s
             | ciencemag.org/pipeline/archives/2018/06/12/an...
        
             | vkou wrote:
             | The goal of medicine is not reducing plaques, the goal is
             | treating Alzheimer's.
             | 
             | If the drug reduces plaques, but doesn't cure Alzheimer's,
             | it's not a 'bad sign'. It simply means the drug doesn't
             | work.
             | 
             | P-value hacking over and over again[1] until we finally get
             | a study that shows us that the drug works is not the
             | solution. [2]
             | 
             | [1] https://xkcd.com/882/
             | 
             | [2] Unless the problem we are solving is "We have too much
             | money that we need to spend on snake oil."
        
               | tootie wrote:
               | I get it, I'm just saying it's not like they're selling
               | essential oils or healing crystals. Reducing plaques
               | could at least plausibly have some benefit. And I'm not
               | arguing necessarily that the FDA are therefore justified,
               | I'm just saying it's not fair to compare this to diet
               | supplements. I was pointed to some other posts by this
               | same guy about how bearish he is on amyloid plaque
               | reduction as a plausible therapy which would have been
               | useful context.
        
               | jolux wrote:
               | > I get it, I'm just saying it's not like they're selling
               | essential oils or healing crystals.
               | 
               | You might have more of an argument here if this drug was
               | only going to cost as much as essential oils or healing
               | crystals, ironically. Would you suggest somebody go into
               | debt for treatment with this product? It's likely to be
               | quite expensive.
        
             | jolux wrote:
             | This is an epistemologically leaky argument. The goal of an
             | Alzheimer's drug is not to reduce amyloid plaques, it's to
             | treat Alzheimer's. There is, as of now, no evidence that it
             | does so. Giving people false hope of treating a horrible
             | disease does actually seem more unethical than not giving
             | them the treatment at all.
        
       | tunesmith wrote:
       | 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 wrote:
         | 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.
        
         | rossdavidh wrote:
         | 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 wrote:
         | > 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.)
        
       | azinman2 wrote:
       | Somewhat tangential question: there are all these new drugs with
       | -mab and -ab suffixes. Why is that?
        
         | xenophon wrote:
         | 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 wrote:
         | See here:
         | https://en.m.wikipedia.org/wiki/Nomenclature_of_monoclonal_a...
        
           | azinman2 wrote:
           | Wow that's really interesting. Good to see it's less random
           | than these words seem to be! Thanks
        
         | robbiep wrote:
         | 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)
        
       | Invictus0 wrote:
       | Is there any way that this decision could be overturned, and is
       | that at all likely?
        
         | yborg wrote:
         | 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.
        
       | Metacelsus wrote:
       | 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?
        
         | CaliforniaKarl wrote:
         | 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-...
         | 
         | [1]: https://www.worldometers.info/world-population/
         | 
         | [2]: https://www.fda.gov/advisory-committees
        
         | adrianN wrote:
         | 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.
        
         | CarelessExpert wrote:
         | 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!
        
       | ProjectArcturis wrote:
       | The FDA just allowed Biogen to suck hundreds of billions out of
       | Medicare to pay for a drug that probably doesn't work.
        
         | BurningFrog wrote:
         | 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 wrote:
           | > 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 wrote:
             | 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...
        
             | tptacek wrote:
             | Not for nothing, but, despite all the airtime this issue
             | gets, my understanding is that pharmaceuticals are a pretty
             | small component of health care spending; like, if you
             | zeroed it out, you'd get less than a grocery store
             | discount.
        
               | hn_throwaway_99 wrote:
               | I disagree. See
               | https://www.politifact.com/factchecks/2019/feb/22/amy-
               | klobuc... (drug costs come between 15-17% of total
               | spending). And given how you can divvy up spending
               | (drugs, facilities, doctors, nurses, admin staff,
               | overhead, etc.), one sixth of total spending seems like a
               | very large amount.
               | 
               | And, it's especially the case that for certain
               | individuals (this page also made the top of HN today,
               | https://www.goodrx.com/blog/most-expensive-drugs-period/)
               | that drug costs are a gargantuan, total-lifetime-salary
               | kind of expenditure.
        
             | tomsto wrote:
             | 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 PS/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.
        
           | NationalPark wrote:
           | Considering their own advisory committee advised against
           | approving the drug because of the lack of evidence that it
           | works, the FDA doesn't really judge the medical evidence very
           | well!
        
         | an_opabinia wrote:
         | > 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?
         | 
         | In a sense, this is how it's sort of always worked. The
         | approval process is about protecting investors. If a drug is
         | good it's usually pretty obvious. When it's not obvious,
         | efficacy in a more abstract sense must account for cost, which
         | is out of the FDA's jurisdiction.
         | 
         | The real problem with its organization is that it is, as you're
         | saying, Medicare's procurement agent. But it is not empowered
         | to consider cost.
        
       | PragmaticPulp wrote:
       | 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.
        
         | adrianmonk wrote:
         | > _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._
         | 
         | Hmm, what if we added a new phase where it's approved but can
         | only be sold at a low, regulated price? Then if/when it is
         | proven effective, they can transition to charging more.
         | 
         | Without getting into whether it's actually a good idea, in
         | theory the high prices are meant to be a reward that makes it
         | worthwhile to invest in drug development. Delaying the reward
         | would still allow that incentive but keep it tied to actually
         | creating drugs that work while still allowing patients earlier
         | access.
        
           | rolleiflex wrote:
           | The risk with that is that it creates a 'perverse' incentive
           | for the FDA to not fully approve drugs because the approved
           | drugs might shoot up in price 1000x the moment they exit the
           | 'purgatory approval', and granting the official approval
           | might kill some people who can afford the purgatory price,
           | but not the fully approved official one.
        
             | pontifier wrote:
             | So lock in the price for the ones that started taking it
             | before it was fully approved.
        
               | rolleiflex wrote:
               | That then would create the 'perverse' incentive for
               | poorer people who are dying of major diseases to sign up
               | for any and all trials possible to lock in prices,
               | regardless of relevance, and make things much, much worse
               | for themselves due to misuse. Richer people would not do
               | that since they can pay the full price without locking
               | the old price in, so this risks converting the sick and
               | poor people already battered by life into lab rats.
               | 
               | If you instead don't enforce the requirement to actually
               | take the drugs to lock in the price, then everyone signs
               | up for everything and your drug companies will stop
               | making any new drugs.
        
         | mkehrt wrote:
         | Mean drug effect is possibly a bad metric to measure. If the
         | distribution is bimodal, or has very high variance, the FDA
         | could take that into account when approving a drug.
         | 
         | I believe SSRIs often vary in effectiveness, for example; some
         | people are just very good responders. Fortunately, their mean
         | effectiveness is high enough.
         | 
         | (Not a doctor, etc)
        
         | nceqs3 wrote:
         | Medicare would pay no where close to 56k/year. There are
         | mandated rebates and price controls in medicare.
        
           | amercer777 wrote:
           | Medicare would indeed pay close to that price. Medicaid would
           | see a rebate but would still be on the hook for roughly 75%
           | of the list price initially.
        
         | adrianN wrote:
         | Hopefully, eventually we'll be able to figure out _why_ a drug
         | works for one person but not for the next so that we can get
         | pinpointed approvals for just that subpopulation.
        
           | sneak wrote:
           | A simpler solution is to get rid of the approval process and
           | let people operate their own bodies how they personally
           | choose.
        
             | majormajor wrote:
             | So the solution to the problem of doctors and medicine
             | makers not being able to figure out what's gonna be safe
             | and effective for whom is to just tell the patient to try
             | to figure that out on their own?
        
               | sneak wrote:
               | We know the top-down approach is ineffective. Is the
               | other one worse?
        
               | tptacek wrote:
               | Yes. We don't have to wonder; we have a supplements
               | industry to show us what happens.
        
               | 35fbe7d3d5b9 wrote:
               | The terms "patent medicine" and "snake oil" didn't just
               | appear from the aether.
        
               | dnautics wrote:
               | Choosing != Figuring out
        
         | jasonlaramburu wrote:
         | I think the FDA was in a difficult spot. There have been no new
         | Alzheimers drugs in decades and patients are desperate for
         | treatments. There is reason to believe that beta amyloid
         | blockers need to be given in the earliest stages of Alzheimers
         | (when diagnosis is difficult) to have any impact on cognitive
         | decline. The trials did not focus on early stage patients, so
         | there may be positive impacts if it can be given early enough.
        
           | hmahncke wrote:
           | The trial did focus on early stage patients - mild cognitive
           | impairment (MCI) and early stage AD to be precise.
        
           | compiler-guy wrote:
           | Great! So let's figure out a way to make this study happen so
           | that the drug can be given effectively (if it does indeed
           | work) rather than have a blanket approval of a drug that
           | lacks any proof of efficacy at all.
           | 
           | That a drug hasn't been approved for a treatment in years is
           | no reason to approve one that doesn't work.
        
             | majormajor wrote:
             | > So let's figure out a way to make this study happen so
             | that the drug can be given effectively (if it does indeed
             | work) rather than have a blanket approval of a drug that
             | lacks any proof of efficacy at all.
             | 
             | It isn't a blanket approval, but it does sound way too
             | generous in terms. From the linked article:
             | 
             | > 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.
        
             | jasonlaramburu wrote:
             | I guess the thinking is that it could take years to know
             | whether it's working or not through an RCT. I believe they
             | are currently allowed 9 years by FDA to show efficacy. If
             | the side effects aren't significant why not let people in
             | need try it?
        
               | robbiep wrote:
               | The side effects are significant. It comes with some risk
               | of brain bleeds and a high risk of cerebral oedema in
               | patients who have APOe4. This is an important genetic
               | profile for those who understand Alzheimer's, as
               | homozygotes for APOe4 are 12x more likely to develop
               | Alzheimer's.
               | 
               | This is a cop out decision by the FDA. Efficacy can be
               | determined by a RCT - instead a decision was made which
               | supports biogen's share price
        
         | bsder wrote:
         | > In their case, it's likely that the disease has multiple
         | causative factors and the drug in question only treats one
         | specific cause.
         | 
         | The problem is that _every_ drug that has targeted amyloid has
         | failed to do jack shit in _any_ cohort--not early, not late,
         | not alien--none of them.
         | 
         | Any _rational_ science system would conclude  "The amyloid
         | hypothesis for Alzheimer's is _WRONG_. "
         | 
         | But, no, the bio people just plow on further because amyloid
         | gets published, and funded, and, now, approved.
         | 
         | One day we'll look at this time as the alchemy period of neuro.
        
         | shkkmo wrote:
         | 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 wrote:
           | 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?????
        
         | phkahler wrote:
         | >> 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.
         | 
         | The usual story for why we allow patenting of drugs and high
         | prices is that development is very costly - particularly the
         | cost of doing trials. If they're going to allow this on the
         | market without trials that show efficacy, the least they can do
         | would be to allow generics at low prices while we're doing the
         | efficacy testing on the general public ;-) </sarcasm>
        
       | sparsely wrote:
       | 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). " 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-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 wrote:
         | The article mentions the public pressure brought by these
         | organisations. They may come to regret that pressure.
        
       | deeviant wrote:
       | 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".
        
         | PragmaticPulp wrote:
         | 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 wrote:
           | This is one of those comments I want to bookmark and come
           | back to in a decade. :)
        
         | zamalek wrote:
         | > 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.
        
         | HarryHirsch wrote:
         | It already happened in Britain over cancer medication:
         | 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.
        
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