I have been a supporter of Cures Within Reach, a nonprofit that focuses on repurposing drugs, especially for rare diseases. https://www.cureswithinreach.org
They have funded some important repurposed-drug studies for Huntingtons Disease, which runs in my family. For a disease like this, it's never going to make sense for major pharmaceutical companies to invest the effort to develop entirely new drugs, but by repurposing existing drugs, it gives people living with rare diseases a chance to ease symptoms.
> For a disease like [Huntingtons], it's never going to make sense for major pharmaceutical companies to invest the effort to develop entirely new drugs
This is ... not correct.
Roche, Regeneron, and Novartis all have novel HD drugs under development in tandem with smaller labs (Ionis, Alnylam, and PTC respectively), and then smaller labs like uniQure and Wave Life Sciences do too. Novartis have already dropped $1bn on the partnership with a committed $2b more. In addition, there are a bunch of incentive schemes for diseases like HD: both the FDA and EMA have offered orphan-drug designation to therapies for HD, the FDA does expedited programmes and can offer RMAT designation for drugs like AMT-130.
With some luck (which is always in short supply for HD treatments, sadly), people with the disease might be able to get a single-injection treatment in the next 12 months[0].
I’m currently on Spravato, which is fully emblematic of how broken the incentives in the US healthcare system are.
Spravato is esketamine - a modified version of ketamine. Ketamine is made up of mirror image molecules and esketamine is the right-handed molecule. They did this because ketamine is off-patent so they needed to modify it in order to patent it, however there is evidence that esketamine is a less effective treatment than ketamine.
It’s very cheap for me but my insurance company pays about $17k a month for this treatment. Ketamine would be a more effective treatment that would be super cheap for them, but they don’t do it because it’s not FDA-approved. So they’re paying a fortune for a less effective treatment.
It would be in the insurance companies’ interests to band together to fund the research so they can save huge amounts of money in the long term but they do not do this.
> It would be in the insurance companies’ interests to band together to fund the research so they can save huge amounts of money in the long term but they do not do this.
Insurance companies do not want cheaper care.
In the US, insurance companies must spend 80% of premiums on care. So if you pay $1k/mo, they have to pay out at least $800/mo in care. (Not to you specifically, but averaged out across all subscribers.)
This is a cap on their potential profits. They always have to pay out 80% of premiums for care, so how do they make more money?
Well, imagine care is twice as expensive. Instead of paying $800, they have to pay $1600. That sounds worse, but, instead of $200/mo, they now $400/mo for themselves!
So, no, paradoxically, it is not in the interest of people paying for the treatment to save money. Quite the opposite.
Such studies are great but there is no regulatory pathway to extend the use of existing drugs for new indications of use without the consent of the manufacturer (or becoming a manufacturer yourself).
This means such studies can give more clarity on which off-label use is beneficial but it can't be an officially allowed usage.
Also a LDN user, that drug saved my life. I bought it from a shady dude online, the initial effect was so strong that I thought they shipped me meth instead - that wore off after a week but the lifting of the brain fog persisted.
It didn’t have that sort of immediate, intense effect for me (though yours isn’t the only account like this that I’ve seen) but I’m still happy with the outcome; it dropped my average 1-to-10 pain score by about two points at three months.
It is a rare side effect, I helped a bunch of people (~50) get LDN, primarily for LongCovid, and only one other had a similar ‘too much energy’ effect and both of us have multiple TNXB SNPs and a very similar rare personality profile. I think the brain is so starved for dopamine at that point that it becomes hyper sensitive. I do miss the extra high energy but I also know that isn’t maintainable and I try to err on the side of caution.
I’ve had ME/CFS my whole life but the third covid vaccine shot sent me to new lows, to the point LDN just wasn’t cutting it anymore. These days I take a combo of modafinil in the morning and amitryptiline at night. And low dose ozempic has been super helpful as well. I was researching GLP1As prior to the current craze because I was worried about hyper sensitivity so I waited for more data before trying, I started at 1/100th the normal starting dose and still got temporary gastroparesis. These days I take a more regular dose of 1mg/wk but it also seems that my body has largely normalized as the hypersensitivities have worn off. Probably a good sign that I’ve successfully addressed actual deficiencies.
The doctors are assuming liability or let the patient sign waivers, which I guess is fine. But the lack of a pathway prevents a lot of commercial possibilities. For instance it is almost impossible to build a business around supporting off-label use cases (for instance selling necessary accessories).
I have some difficult-to-treat medical issues and about 1/3 of the handful of pills I take every day are off-label. I think when you get into less common medical concerns off-label use becomes much, much more frequent.
E.g. gabapentin is an anti-seizure medication that has been found to reduce neuropathic pain as well. It has shot up to the 5th most prescribed medication in the last decade as it has replaced long-term opioid use for new chronic neuropathic pain patients. This is 100% off-label and is prescribed by everyone from NPs all the way up to neurosurgeons for this purpose.
I’ve never been asked to sign a waiver and I can’t imagine that for-profit hospitals would allow their doctors to prescribe off-label medications willy-nilly if they represented big liability. (I don’t know this for sure, this is just what my experience implies.)
Yup, I've seen this sort of off label prescription at least 3 times.
A lot of drugs require almost no evidence (especially if they are relatively cheap or common) to be given to the insurance company when they are prescribed. And if you are willing to pay for it, you can always pay out of pocket if insurance is being a pain.
That presumably has to do with the risk profile of the medications you've taken. If there was a high risk of devastating side effects and it was off label presumably the prescriber wouldn't be willing to take on the liability.
I would wager if those waivers actually did anything they'd boilerplate a generic version of it in the legal mumbo jumbo you have to sign even if you come in to have the doctor look at a stubbed toe.
To get a drug approved you have to go through regulatory approval for a particular use. If the fuck-fuck game is you can just off-label for whatever but only if first approved by the FDA to solve some other problem, why not just bypass the bullshit and get straight to the point of approving the drug without any approved use? Oh yes, because that assures the barriers to entry are arbitrarily higher, and Pfizer and other ilk can insulate themselves from competition. Thanks FDA!
Like a lot of the systems we have today, it grew from good intentions. We need to figure out a way to refresh our systems without throwing them away. The current system does provide new drugs and benefit. The question is is it limiting, and are the tradeoff of those limits worth while.
In other words it takes hard work, with politically risky outcomes and an upside that becomes invisible as far as political careers go. We need to figure out how to refresh our systems in an environment where that type of thing just stumbles along. Maybe a couple of politicians elected who have lost out because of the status quo, but that want to improve it not throw it away. Maybe working with them to motivate them to take it on as a pet project and move things.
If we're just letting doctors yolo* off-label, i have no problem with that, but that functionally relegates FDA protections to testing risk profile at some particular dose regimen, with a bunch of extra bullshit tacked on that is highly inefficient process for off-label use even if partially applicable.
It's pretty clear if you're allowing off-label use you can just gate dose-risk profile at one gate and then just add additional gates for on-label uses if you want to approve one.
Of course the issue is the FDA regulator gets the hammer and damned if anything goes wrong but nothing good happens to them if they approve something. So they have no real incentive to approve anything except ideological satisfaction to whatever extent it lives within their mind, plus whatever revolving door benefits industry is offering them.
Probably best to reward the FDA employees for approving good drugs so that the prisoners' dilemma doesn't always fall back to erring on the side of denials, and being easier on them for taking some risk that approves bad drugs to the point they're willing to take some risk to let potentially good drugs through. The regulator doesn't get to see all the bad they cause by not approving drugs because that's invisible, and that's the unintended consequence of their activities and something they're not really held to account for.
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>Doctors aren't yoloing it.
If you take offense, call it whatever the hell you want, I was using it in the context of using a drug for a non-approved off-label use. You're making no legal distinction, it's not an FDA approved use and telling the FDA you have some evidence elsewhere but you won't be going through the process to approve it doesn't mean dick to the approval process anymore than my disapproved use of the world "yolo" to refer to same does. If the best my counterparties have is disapproving of "yolo" I rest my case.
What's happening is further research on the medicines are being done which show medicinal benefits for off label use. In many cases, it's researchers seeing a drug has a known side effect and saying "Hmm, I wonder if that side effect can counter this symptom".
What's lacking is the final FDA approval for the drugs being used for these off label treatments. That's because these drugs have to go through all the same tests that are required to get FDA approval in the first place.
IMO, for already approved drugs there should be a faster secondary route to getting these drugs approved for current off label usages. Ideally, it'd be something the FDA itself spearheads in partnership with the likes of the NIH.
> For instance it is almost impossible to build a business around supporting off-label use cases (for instance selling necessary accessories).
There is no need for a business. Off label use is hacking around the existing commercial and regulatory system. The innovation to be had is fixing said commercial and regulatory system, not another business. Make cheap drugs or medical supplies, distribute them to those in need with as little margin and risk to the patient as possible. This is a utility system masquerading as a market. More duct tape by way of new businesses is suboptimal.
Yes, but that isn't relevant to what happens after the type of trials described in the article, which tends to happen when the patents are no longer relevant. As the article points out, while the drugs are patented, the manufacturers themselves are generally very interested in repurposing because it broadens their market. The article is discussing trials that mostly happens once the patents have expired.
A research group can file for a new drug application (or abbreviated new drug application) for an existing drug. There is no mandate that an NDA sponsor be a manufacturer or the existing manufacturer.
Only the entity holding an approved NDA can file a supplemental NDA but that’s not the only path.
The real reason no one files for off label use is that there’s high cost and little to no practical benefit to doing so.
This isn't completely true at least in the UK. It is simply that the manufacturer is no longer responsible legally. The GMC allow prescibing of unlicensed meds. However the change needs to be made to the pathway. So many issues in the NHS has been due to pathway problems.
I'm in the US, and there are a couple of wrinkles to this: insurance typically won't cover off label use, so patients end up paying the full cost of the medication, and if there is a big enough market, I believe companies can patent the new use even if the patents for the original use have run out.
Doctors here are allowed to prescribe them though.
Insurance will have prior authorization rules for certain drugs that are expensive that require the doctor to submit documentation of the condition, but in most cases the common medication is simply covered if prescribed. The insurance company does not receive documentation of every condition for every prescription to determine if the prescription is on label or off label.
Insurance companies can and do also support some off label treatments that are commonly used under their prior auth requirements.
I don’t know why there are so many comments in this thread making confident assertions that off label prescribing or insurance or so uncommon. This happens all day long at doctors offices and pharmacies.
Agreeing. There is a ton of blatant misinformation being shared in this thread by people who seem utterly confident despite their apparently complete ignorance.
"COM claims can be difficult to gain for repurposed compounds, as the patentee must somehow differentiate their patent claims over what is in the public domain and present data that the drug is a credible candidate for the new indication [41, 42]."
Specialists keep up with the latest research in their domains and talk with other specialists in their field. They usually know about these things before their patients discover them spontaneously.
You can read a lot of published papers on PubMed by searching for a condition or drug. You should be aware that there are a lot of papers published that say disease A can be treated with drug or supplement B that fail to replicate if anyone else tries it. It takes some practice to recognize when a treatment represents a real trend as opposed to a single quack doctor looking for a status boosting publication with some questionable claims.
Big medical systems will post their clinical trails quarterly or so. If you have a big medical system near you you can sign up for emails. I imagine universities would have a mailing list too, if they regularly did clinical trials.
If every drug created with taxpayer dollars at government-funded research institutions was open-sourced, there would be a collapse in monopoly control of drug manufacturing and that would lower prices significantly.
The question is then, if corporations can no longer acquire IP rights to drugs created by taxpayer-funded research programs and transferred to their exclusive control (eg if Bayh-Dole is repealed in the USA), who will invest in clinical trial costs that need to be recouped via a period of inflated pricing?
The answer is government-funded, transparent, and statistically-robust clinical trials of drugs. Once a clinical trial is complete, private manufacturers can compete to produce the drugs at the lowest price by optimizing their manufacturing pipelines against a final product standard regulated by the FDA. If they want to run their own R & D divisions for drug development outside the taxpayer-financed university system to generate exclusive private patents, they certainly can - on their own dime. That’s an investment decision.
If you need to review why this government-linked, tightly regulated system is needed for drugs with clinical effects, just look up ‘patent medicine disasters of the early 20th century’.
This all assumes that the government will do an equal or better job spending money than companies that rely on spending that money well to exist.
What will actually happen is that the government department of repurposing drugs will be efficient once and then get their budget reduced and never be efficient again. Next time they'll make sure to spend every last cent and not worry about the over budget boondoggle that's three years late because their job isn't to get stuff done, it's to make sure politicians can say their doing something on the campaign trail.
Notice I was sure to include ‘revival of corporate R & D divisions’ in the argument? Bell Labs is the archetype - if corporations can do a better job of applied R & D, let them. If corporations are upset about publicly funded research generating open-source discoveries that upset the monopolistic apple cart, that’s not an argument about improving efficiency - that’s an argument about maximizing profits and investor return, not for efficient new drug discovery or old drug repurposing.
The real question is, what is the metric of ‘success’ - improved public health for the entire population at low cost, or bloated returns for pharmaceutical investors?
fascinating! I'm sure there's quite a bit that can be learned through appropriate research - pathways to solve problems that haven't been thought of before
the thing is while something is better than nothing, new drug development is critical
there is absolutely no cure for certain types of long-covid and me-cfs right now
no repurposing any drug is going to cure it, they've tried everything after six years
it will take a decade to have anything even in the pipeline and won't emerge from the USA because all medical and science research investment by the government has been destroyed by Russell Vought and Heritage Foundation
JAK-STAT inhibitors will be a big treatment, not a cure, but they cost thousands per month in the USA because generics aren't allowed
> the thing is while something is better than nothing, new drug development is critical
> there is absolutely no cure for certain types of long-covid and me-cfs right now
> no repurposing any drug is going to cure it, they've tried everything after six years
Then repurposing should free up resources for new drug development for those conditions that it can't address.
Sounds like a win-win, unless the goal is somehow not to most efficiently allocate resources to maximize health outcomes. But at least in the US, that's clearly not the goal.
The prices of drugs in the USA are especially high. This is interesting
because the USA claims to pursue a maximum capitalistic society - but if
this were the case, you'd have competition in a free market. But you don't
have that. You have a cartel (or rather more than one).
A pure capitalistic society works on assumptions that are not real. People
are often cheaters. This would have to be taken into account. But when you
have an orange Al Capone in charge, it is pillage day. Even before the orange
King you had heavily overcharged prices in the health care system. You need
to realise that you have a mafia in charge that does not want to change this
system. Why kill the cow that you can milk for free?
> This is interesting because the USA claims to pursue a maximum capitalistic society
No it doesn't. This is silly.
Drug prices in the US are high for non-generic drugs because patent law gives the patent holder an artificial government-granted monopoly, which is blatantly not "pure" or "maximum capitalistic".
Generic drugs - where the free market does apply - in the US are as cheap or cheaper than in other countries. See [0]:
U.S. prices for brand-name originator drugs were 422 percent of prices in
comparison countries, while U.S. unbranded generics, which we found account for 90
percent of U.S. prescription volume, were on average cheaper at 67 percent of
prices in comparison countries, where on average only 41 percent of prescription
volume is for unbranded generics.
The maximum libertarian alternative to patents isn't free-for-all copying, it's trade secret formulas - e.g. Coca Cola. Drug patents actually exist as a compromise given the clear need for the state to force companies to publish their drug formulas for research. Allowing companies to just keep their drugs secret would be even more capitalistic, and would increase drug prices even more.
This is where prizes come in. If you create a drug and keep it secret, the government can grant you a large prize as an offer to reveal your secret.
This is a much better compromise. The company will end up with more money(and faster!) as a result of this prize than under a patent system - since the patent system induces dead-weight losses, and the government will end up with more lives saved.
They keep their processes secret instead under the current system, achieving a "trade-secret" like result for some drugs. For some drugs it achieves the same thing because finding a practical economic synthesis is the hard part rather than coming upon a small bit of chemical that is proven to be effective. For others it wouldn't matter whether you kept it secret or not, someone would isolate and characterize it and reverse engineer a practical synthesis.
The biggest value protector arguably of the patent-FDA approval process is on the FDA side, who create massive barriers to entry that mitigate close unpatented chemical competitors from outside the pharma oligopoly from competing.
Is the patent not for the synthesis route itself, rather than the drug? Someone can't just plop down a chemical formula on a piece of paper and patent that, can they?
I'm not really happy with the current system either - I tend to think that the state should just mandate that all medical research be fully published, and either have companies compete on research and manufacturing, or pay for it directly if it can't be made to work as a private business. My point was just that this is very much not a capitalist or libertarian position.
"Drug prices in the US are high for non-generic drugs because patent law gives the patent holder an artificial government-granted monopoly, which is blatantly not "pure" or "maximum capitalistic"."
This is very much capitalistic. It's not competitive markets (which are good for consumers) but capitalists hate competition once they have made it to the top.
> This is interesting because the USA claims to pursue a maximum capitalistic society
I don’t know why you think this. The US is not a maximally capitalist society. The reason drug prices are so high is due to regulations restriction who can manufacture them due to government-granted temporary monopolies through patent law.
If the US was maximally capitalist it would be a free for all with no patent protection.
> If the US was maximally capitalist it would be a free for all with no patent protection.
The much more likely alternative in a maximally capitalist / free market maximalist society would be keeping all drug formulas as trade secrets, and thereby having all drugs as branded, no generics whatsoever (or few - perhaps some substances could be reverse engineered). In such a society, having the state force companies to publish their formulas would be seen as unacceptable interference in the free market, almost certainly.
Look at the development of price and quality of something that is outside the regulated medical system, like eg Lasik, and everything within that system. Its like night and day.
If we had proper competition and price discovery, things would be much better.
Are you under the impression that dentists are under competitive pressure? The labour supply is artificially limited, similar to other doctor specialisations.
Dentists are only slightly more honest as a profession than Chiropractors. More than half of the one's you meet are outright fraudsters/charlatans/scammers. Most who work in that business will reincarnate as cockroaches or durian fruits.
Are you in the US? This is not my experience at all. I've paid in US <2000 for dental invasive surgery including general anesthesia straight cash. That's approaching prices for medical care in Mexico.
I have been a supporter of Cures Within Reach, a nonprofit that focuses on repurposing drugs, especially for rare diseases. https://www.cureswithinreach.org
They have funded some important repurposed-drug studies for Huntingtons Disease, which runs in my family. For a disease like this, it's never going to make sense for major pharmaceutical companies to invest the effort to develop entirely new drugs, but by repurposing existing drugs, it gives people living with rare diseases a chance to ease symptoms.
> For a disease like [Huntingtons], it's never going to make sense for major pharmaceutical companies to invest the effort to develop entirely new drugs
This is ... not correct.
Roche, Regeneron, and Novartis all have novel HD drugs under development in tandem with smaller labs (Ionis, Alnylam, and PTC respectively), and then smaller labs like uniQure and Wave Life Sciences do too. Novartis have already dropped $1bn on the partnership with a committed $2b more. In addition, there are a bunch of incentive schemes for diseases like HD: both the FDA and EMA have offered orphan-drug designation to therapies for HD, the FDA does expedited programmes and can offer RMAT designation for drugs like AMT-130.
With some luck (which is always in short supply for HD treatments, sadly), people with the disease might be able to get a single-injection treatment in the next 12 months[0].
0: https://en.hdbuzz.net/the-other-shoe-drops-uniqure-shares-pl...
I'm on my cell phone and I couldn't figure out what diseases can be treated on the site. I'd say it's donor focused and not patient focused
Not exactly what you asked for, but this page lists their impact: https://www.cureswithinreach.org/about-us-repurposing-resear...
Have you looked into UniQure / Clearpoint Neuro ?
Exciting stuff, if it gets FDA approved.
I’m currently on Spravato, which is fully emblematic of how broken the incentives in the US healthcare system are.
Spravato is esketamine - a modified version of ketamine. Ketamine is made up of mirror image molecules and esketamine is the right-handed molecule. They did this because ketamine is off-patent so they needed to modify it in order to patent it, however there is evidence that esketamine is a less effective treatment than ketamine.
It’s very cheap for me but my insurance company pays about $17k a month for this treatment. Ketamine would be a more effective treatment that would be super cheap for them, but they don’t do it because it’s not FDA-approved. So they’re paying a fortune for a less effective treatment.
It would be in the insurance companies’ interests to band together to fund the research so they can save huge amounts of money in the long term but they do not do this.
> It would be in the insurance companies’ interests to band together to fund the research so they can save huge amounts of money in the long term but they do not do this.
Insurance companies do not want cheaper care.
In the US, insurance companies must spend 80% of premiums on care. So if you pay $1k/mo, they have to pay out at least $800/mo in care. (Not to you specifically, but averaged out across all subscribers.)
This is a cap on their potential profits. They always have to pay out 80% of premiums for care, so how do they make more money?
Well, imagine care is twice as expensive. Instead of paying $800, they have to pay $1600. That sounds worse, but, instead of $200/mo, they now $400/mo for themselves!
So, no, paradoxically, it is not in the interest of people paying for the treatment to save money. Quite the opposite.
So in Ketamine approved as a treatment in other countries but not in the US?
Related, one of my all time favorite articles: https://www.propublica.org/article/revlimid-price-cancer-cel...
Thank you, really liked this one.
This was so hurtful and blood boiling to read. How is stuff like this allowed to happen?
The Price of Remission - https://news.ycombinator.com/item?id=43925396 - May 2025 (93 comments)
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If you haven't watched this talk by Matt Might on Precision Medicine with MiniKanren, you will surely find it inspiring https://www.youtube.com/watch?v=Rt3XyeFHvt4
Such studies are great but there is no regulatory pathway to extend the use of existing drugs for new indications of use without the consent of the manufacturer (or becoming a manufacturer yourself).
This means such studies can give more clarity on which off-label use is beneficial but it can't be an officially allowed usage.
There tens of millions of people being treated off-label.
Can confirm. LDN user here.
Also a LDN user, that drug saved my life. I bought it from a shady dude online, the initial effect was so strong that I thought they shipped me meth instead - that wore off after a week but the lifting of the brain fog persisted.
It didn’t have that sort of immediate, intense effect for me (though yours isn’t the only account like this that I’ve seen) but I’m still happy with the outcome; it dropped my average 1-to-10 pain score by about two points at three months.
It is a rare side effect, I helped a bunch of people (~50) get LDN, primarily for LongCovid, and only one other had a similar ‘too much energy’ effect and both of us have multiple TNXB SNPs and a very similar rare personality profile. I think the brain is so starved for dopamine at that point that it becomes hyper sensitive. I do miss the extra high energy but I also know that isn’t maintainable and I try to err on the side of caution.
I’ve had ME/CFS my whole life but the third covid vaccine shot sent me to new lows, to the point LDN just wasn’t cutting it anymore. These days I take a combo of modafinil in the morning and amitryptiline at night. And low dose ozempic has been super helpful as well. I was researching GLP1As prior to the current craze because I was worried about hyper sensitivity so I waited for more data before trying, I started at 1/100th the normal starting dose and still got temporary gastroparesis. These days I take a more regular dose of 1mg/wk but it also seems that my body has largely normalized as the hypersensitivities have worn off. Probably a good sign that I’ve successfully addressed actual deficiencies.
The doctors are assuming liability or let the patient sign waivers, which I guess is fine. But the lack of a pathway prevents a lot of commercial possibilities. For instance it is almost impossible to build a business around supporting off-label use cases (for instance selling necessary accessories).
I have some difficult-to-treat medical issues and about 1/3 of the handful of pills I take every day are off-label. I think when you get into less common medical concerns off-label use becomes much, much more frequent.
E.g. gabapentin is an anti-seizure medication that has been found to reduce neuropathic pain as well. It has shot up to the 5th most prescribed medication in the last decade as it has replaced long-term opioid use for new chronic neuropathic pain patients. This is 100% off-label and is prescribed by everyone from NPs all the way up to neurosurgeons for this purpose.
I’ve never been asked to sign a waiver and I can’t imagine that for-profit hospitals would allow their doctors to prescribe off-label medications willy-nilly if they represented big liability. (I don’t know this for sure, this is just what my experience implies.)
Yup, I've seen this sort of off label prescription at least 3 times.
A lot of drugs require almost no evidence (especially if they are relatively cheap or common) to be given to the insurance company when they are prescribed. And if you are willing to pay for it, you can always pay out of pocket if insurance is being a pain.
> I’ve never been asked to sign a waiver
That presumably has to do with the risk profile of the medications you've taken. If there was a high risk of devastating side effects and it was off label presumably the prescriber wouldn't be willing to take on the liability.
Do you know that for a fact or are you just guessing?
I would wager if those waivers actually did anything they'd boilerplate a generic version of it in the legal mumbo jumbo you have to sign even if you come in to have the doctor look at a stubbed toe.
That's not my experience at all, my doctor's have prescribed plenty of things off label. No special waivers.
Off label prescribing is extremely common.
This isn’t a new or novel concept. Doctors manage patients with off-label prescriptions all day long.
To get a drug approved you have to go through regulatory approval for a particular use. If the fuck-fuck game is you can just off-label for whatever but only if first approved by the FDA to solve some other problem, why not just bypass the bullshit and get straight to the point of approving the drug without any approved use? Oh yes, because that assures the barriers to entry are arbitrarily higher, and Pfizer and other ilk can insulate themselves from competition. Thanks FDA!
Like a lot of the systems we have today, it grew from good intentions. We need to figure out a way to refresh our systems without throwing them away. The current system does provide new drugs and benefit. The question is is it limiting, and are the tradeoff of those limits worth while.
In other words it takes hard work, with politically risky outcomes and an upside that becomes invisible as far as political careers go. We need to figure out how to refresh our systems in an environment where that type of thing just stumbles along. Maybe a couple of politicians elected who have lost out because of the status quo, but that want to improve it not throw it away. Maybe working with them to motivate them to take it on as a pet project and move things.
If we're just letting doctors yolo* off-label, i have no problem with that, but that functionally relegates FDA protections to testing risk profile at some particular dose regimen, with a bunch of extra bullshit tacked on that is highly inefficient process for off-label use even if partially applicable.
It's pretty clear if you're allowing off-label use you can just gate dose-risk profile at one gate and then just add additional gates for on-label uses if you want to approve one.
Of course the issue is the FDA regulator gets the hammer and damned if anything goes wrong but nothing good happens to them if they approve something. So they have no real incentive to approve anything except ideological satisfaction to whatever extent it lives within their mind, plus whatever revolving door benefits industry is offering them.
Probably best to reward the FDA employees for approving good drugs so that the prisoners' dilemma doesn't always fall back to erring on the side of denials, and being easier on them for taking some risk that approves bad drugs to the point they're willing to take some risk to let potentially good drugs through. The regulator doesn't get to see all the bad they cause by not approving drugs because that's invisible, and that's the unintended consequence of their activities and something they're not really held to account for.
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>Doctors aren't yoloing it.
If you take offense, call it whatever the hell you want, I was using it in the context of using a drug for a non-approved off-label use. You're making no legal distinction, it's not an FDA approved use and telling the FDA you have some evidence elsewhere but you won't be going through the process to approve it doesn't mean dick to the approval process anymore than my disapproved use of the world "yolo" to refer to same does. If the best my counterparties have is disapproving of "yolo" I rest my case.
Doctors aren't yoloing it.
What's happening is further research on the medicines are being done which show medicinal benefits for off label use. In many cases, it's researchers seeing a drug has a known side effect and saying "Hmm, I wonder if that side effect can counter this symptom".
What's lacking is the final FDA approval for the drugs being used for these off label treatments. That's because these drugs have to go through all the same tests that are required to get FDA approval in the first place.
IMO, for already approved drugs there should be a faster secondary route to getting these drugs approved for current off label usages. Ideally, it'd be something the FDA itself spearheads in partnership with the likes of the NIH.
Problem with FDA is that they try the "one size fits all" what often leads to blocking something that works onlu for a group of patients.
Problem with doctors preascribing against FDA is that it can lead to problems or abuse.
Om an unrelated note, FDA could have been bribed to ban something same way a doctor cpuld have been bribed to prescribe it.
The business is already built given the drug in question is already being manufactured and available on the market.
> For instance it is almost impossible to build a business around supporting off-label use cases (for instance selling necessary accessories).
There is no need for a business. Off label use is hacking around the existing commercial and regulatory system. The innovation to be had is fixing said commercial and regulatory system, not another business. Make cheap drugs or medical supplies, distribute them to those in need with as little margin and risk to the patient as possible. This is a utility system masquerading as a market. More duct tape by way of new businesses is suboptimal.
The article points out that it is typically after patent expiry that the universities and hospitals start looking at repurposing.
The patents aren't hindering off-label use. The hinder commercial exploitation by others.
Yes, but that isn't relevant to what happens after the type of trials described in the article, which tends to happen when the patents are no longer relevant. As the article points out, while the drugs are patented, the manufacturers themselves are generally very interested in repurposing because it broadens their market. The article is discussing trials that mostly happens once the patents have expired.
This is all untrue so far as I understand.
A research group can file for a new drug application (or abbreviated new drug application) for an existing drug. There is no mandate that an NDA sponsor be a manufacturer or the existing manufacturer.
Only the entity holding an approved NDA can file a supplemental NDA but that’s not the only path.
The real reason no one files for off label use is that there’s high cost and little to no practical benefit to doing so.
This isn't completely true at least in the UK. It is simply that the manufacturer is no longer responsible legally. The GMC allow prescibing of unlicensed meds. However the change needs to be made to the pathway. So many issues in the NHS has been due to pathway problems.
That seems wild. Do you have a citation to back that up? And in what country/countries?
I'm in the US, and there are a couple of wrinkles to this: insurance typically won't cover off label use, so patients end up paying the full cost of the medication, and if there is a big enough market, I believe companies can patent the new use even if the patents for the original use have run out.
Doctors here are allowed to prescribe them though.
> insurance typically won't cover off label use
I’m in the US. This is not true.
Insurance will have prior authorization rules for certain drugs that are expensive that require the doctor to submit documentation of the condition, but in most cases the common medication is simply covered if prescribed. The insurance company does not receive documentation of every condition for every prescription to determine if the prescription is on label or off label.
Insurance companies can and do also support some off label treatments that are commonly used under their prior auth requirements.
I don’t know why there are so many comments in this thread making confident assertions that off label prescribing or insurance or so uncommon. This happens all day long at doctors offices and pharmacies.
So much weirdly confident misinformation here. When LLMs do this we can it hallucination.
Can't tell if this comment is agreeing with Aurornis or calling them out.
Agreeing. There is a ton of blatant misinformation being shared in this thread by people who seem utterly confident despite their apparently complete ignorance.
Insurance absolutely covers off label use. And depending on the area of medicine, off label use can be incredibly common (see cardiac pediatrics).
> I believe companies can patent the new use even if the patents for the original use have run out.
This is not true
> insurance typically won't cover off label use
Generally not true but it can be the case, especially for expensive medications
Yes new uses of existing drugs can be patented:
https://www.drugpatentwatch.com/blog/patenting-new-uses-for-...
This is clearly made by an LLM and thus not a credible resource.
From:
https://pmc.ncbi.nlm.nih.gov/articles/PMC9336118/
"COM claims can be difficult to gain for repurposed compounds, as the patentee must somehow differentiate their patent claims over what is in the public domain and present data that the drug is a credible candidate for the new indication [41, 42]."
citing
41 https://pubmed.ncbi.nlm.nih.gov/32241561/
42 https://pubmed.ncbi.nlm.nih.gov/30310233/
> insurance typically won't cover off label use
That's a lie, I get off-label drugs prescribed monthly covered.
How do people needing (and willing to risk) treatment hear about repurposing studies?
Specialists keep up with the latest research in their domains and talk with other specialists in their field. They usually know about these things before their patients discover them spontaneously.
You can read a lot of published papers on PubMed by searching for a condition or drug. You should be aware that there are a lot of papers published that say disease A can be treated with drug or supplement B that fail to replicate if anyone else tries it. It takes some practice to recognize when a treatment represents a real trend as opposed to a single quack doctor looking for a status boosting publication with some questionable claims.
Big medical systems will post their clinical trails quarterly or so. If you have a big medical system near you you can sign up for emails. I imagine universities would have a mailing list too, if they regularly did clinical trials.
You can also search here: https://clinicaltrials.gov/
I was a clinical trial participant once and it was a positive experience for me.
I think in the same way they participate in other clinical trials.
Communities (on-line or off-line) of people who share your disorder, and maybe health care professionals who see many patients with your disorder.
If every drug created with taxpayer dollars at government-funded research institutions was open-sourced, there would be a collapse in monopoly control of drug manufacturing and that would lower prices significantly.
The question is then, if corporations can no longer acquire IP rights to drugs created by taxpayer-funded research programs and transferred to their exclusive control (eg if Bayh-Dole is repealed in the USA), who will invest in clinical trial costs that need to be recouped via a period of inflated pricing?
The answer is government-funded, transparent, and statistically-robust clinical trials of drugs. Once a clinical trial is complete, private manufacturers can compete to produce the drugs at the lowest price by optimizing their manufacturing pipelines against a final product standard regulated by the FDA. If they want to run their own R & D divisions for drug development outside the taxpayer-financed university system to generate exclusive private patents, they certainly can - on their own dime. That’s an investment decision.
If you need to review why this government-linked, tightly regulated system is needed for drugs with clinical effects, just look up ‘patent medicine disasters of the early 20th century’.
This all assumes that the government will do an equal or better job spending money than companies that rely on spending that money well to exist.
What will actually happen is that the government department of repurposing drugs will be efficient once and then get their budget reduced and never be efficient again. Next time they'll make sure to spend every last cent and not worry about the over budget boondoggle that's three years late because their job isn't to get stuff done, it's to make sure politicians can say their doing something on the campaign trail.
Notice I was sure to include ‘revival of corporate R & D divisions’ in the argument? Bell Labs is the archetype - if corporations can do a better job of applied R & D, let them. If corporations are upset about publicly funded research generating open-source discoveries that upset the monopolistic apple cart, that’s not an argument about improving efficiency - that’s an argument about maximizing profits and investor return, not for efficient new drug discovery or old drug repurposing.
The real question is, what is the metric of ‘success’ - improved public health for the entire population at low cost, or bloated returns for pharmaceutical investors?
fascinating! I'm sure there's quite a bit that can be learned through appropriate research - pathways to solve problems that haven't been thought of before
the thing is while something is better than nothing, new drug development is critical
there is absolutely no cure for certain types of long-covid and me-cfs right now
no repurposing any drug is going to cure it, they've tried everything after six years
it will take a decade to have anything even in the pipeline and won't emerge from the USA because all medical and science research investment by the government has been destroyed by Russell Vought and Heritage Foundation
JAK-STAT inhibitors will be a big treatment, not a cure, but they cost thousands per month in the USA because generics aren't allowed
> the thing is while something is better than nothing, new drug development is critical
> there is absolutely no cure for certain types of long-covid and me-cfs right now
> no repurposing any drug is going to cure it, they've tried everything after six years
Then repurposing should free up resources for new drug development for those conditions that it can't address.
Sounds like a win-win, unless the goal is somehow not to most efficiently allocate resources to maximize health outcomes. But at least in the US, that's clearly not the goal.
The prices of drugs in the USA are especially high. This is interesting because the USA claims to pursue a maximum capitalistic society - but if this were the case, you'd have competition in a free market. But you don't have that. You have a cartel (or rather more than one).
A pure capitalistic society works on assumptions that are not real. People are often cheaters. This would have to be taken into account. But when you have an orange Al Capone in charge, it is pillage day. Even before the orange King you had heavily overcharged prices in the health care system. You need to realise that you have a mafia in charge that does not want to change this system. Why kill the cow that you can milk for free?
> This is interesting because the USA claims to pursue a maximum capitalistic society
No it doesn't. This is silly.
Drug prices in the US are high for non-generic drugs because patent law gives the patent holder an artificial government-granted monopoly, which is blatantly not "pure" or "maximum capitalistic".
Generic drugs - where the free market does apply - in the US are as cheap or cheaper than in other countries. See [0]:
[0] https://pmc.ncbi.nlm.nih.gov/articles/PMC11147645/The maximum libertarian alternative to patents isn't free-for-all copying, it's trade secret formulas - e.g. Coca Cola. Drug patents actually exist as a compromise given the clear need for the state to force companies to publish their drug formulas for research. Allowing companies to just keep their drugs secret would be even more capitalistic, and would increase drug prices even more.
This is where prizes come in. If you create a drug and keep it secret, the government can grant you a large prize as an offer to reveal your secret.
This is a much better compromise. The company will end up with more money(and faster!) as a result of this prize than under a patent system - since the patent system induces dead-weight losses, and the government will end up with more lives saved.
They keep their processes secret instead under the current system, achieving a "trade-secret" like result for some drugs. For some drugs it achieves the same thing because finding a practical economic synthesis is the hard part rather than coming upon a small bit of chemical that is proven to be effective. For others it wouldn't matter whether you kept it secret or not, someone would isolate and characterize it and reverse engineer a practical synthesis.
The biggest value protector arguably of the patent-FDA approval process is on the FDA side, who create massive barriers to entry that mitigate close unpatented chemical competitors from outside the pharma oligopoly from competing.
Is the patent not for the synthesis route itself, rather than the drug? Someone can't just plop down a chemical formula on a piece of paper and patent that, can they?
I'm not really happy with the current system either - I tend to think that the state should just mandate that all medical research be fully published, and either have companies compete on research and manufacturing, or pay for it directly if it can't be made to work as a private business. My point was just that this is very much not a capitalist or libertarian position.
I believe you two are arguing the same thing. Maybe the poster could have better worded it "general thought among most people is that the USA ..."
Because you are both absolutely right.
"Drug prices in the US are high for non-generic drugs because patent law gives the patent holder an artificial government-granted monopoly, which is blatantly not "pure" or "maximum capitalistic"."
This is very much capitalistic. It's not competitive markets (which are good for consumers) but capitalists hate competition once they have made it to the top.
Capitalism doesn't serve capitalists. It's built to create an environment where the capitalist, doing what they do best, also serves the community.
Monopolies are anti-capitalism, despite it being something that capital strives for.
This is like being upset that bug spray doesn't actually spray bugs, in fact, it actually deters them.
And yet, the defense of the status quo often relies on the supposition that the US is a capitalist nation, perhaps even a “maximally capitalist” one.
I’ll have to keep this in mind the next time it comes up…
> This is interesting because the USA claims to pursue a maximum capitalistic society
I don’t know why you think this. The US is not a maximally capitalist society. The reason drug prices are so high is due to regulations restriction who can manufacture them due to government-granted temporary monopolies through patent law.
If the US was maximally capitalist it would be a free for all with no patent protection.
> If the US was maximally capitalist it would be a free for all with no patent protection.
The much more likely alternative in a maximally capitalist / free market maximalist society would be keeping all drug formulas as trade secrets, and thereby having all drugs as branded, no generics whatsoever (or few - perhaps some substances could be reverse engineered). In such a society, having the state force companies to publish their formulas would be seen as unacceptable interference in the free market, almost certainly.
You are confusing capitalism with competitive markets. These are very different things.
Look at the development of price and quality of something that is outside the regulated medical system, like eg Lasik, and everything within that system. Its like night and day.
If we had proper competition and price discovery, things would be much better.
On the other hand, dental work, especially anything above basic filings, are prohibitively expensive. I'd say Lasik is the exception, not the rule.
Are you under the impression that dentists are under competitive pressure? The labour supply is artificially limited, similar to other doctor specialisations.
Dentists are only slightly more honest as a profession than Chiropractors. More than half of the one's you meet are outright fraudsters/charlatans/scammers. Most who work in that business will reincarnate as cockroaches or durian fruits.
Are you in the US? This is not my experience at all. I've paid in US <2000 for dental invasive surgery including general anesthesia straight cash. That's approaching prices for medical care in Mexico.
The US is not a capitalist society, it is a liberal society. Capitalism is a consequence of that but it isn't the reason.