I have a little insight here from working with ophthalmologists.
When the article mentions "using a cancer drug to treat a leading cause of blindness" it's talking about using Bevacizumab (brand name Avastin) to treat macular degeneration.
Avastin and Lucentis are molecularly the same drug. The difference is that Avastin isn't packaged to be injected into eyeballs, and Lucentis is. Also, Avastin costs about $50/dose, and Lucentis costs around $1,500/dose.
There are compounding pharmacies that will repackage Avastin into a format that can be injected into eyeballs.
However, many ophthalmologists are hesitatnt to use Avastin because that process introduces the potential for contamination. Not that it happens frequently, but every ophthalmologist I know lives in fear of introducing an infection into their patient's eyeballs. And what level of risk is worth saving $1,450 per dose on an injection? 1/100? 1/1000?
I know at least one ophthalmologist who would use Avastin, but would culture a sample from every batch she got from the compounding pharmacy, and had at least one batch that cultured bacteria.
Assumedly, if she hadn't, every patient she injected with that batch would have been at risk of contracting endophthalmitis, and endophthalmitis is no joke. Not infrequently, it can mean losing vision.
I know several of that ophthalmologist's colleagues who had been using compounded Avastin to try and save their patients money, stopped after that incident.
I don't really have a conclusion beyond "drug pricing is insane and the issue is complex for providers."
Compounding pharmacies can get injectibles wrong in a deadly way. Many families are still waiting for justice after the MECC pharmacy caused the deaths of 64 people:
"On July 7, 2021, Barry Cadden's original 9-year sentence was increased to 14.5 years. An appeals court court decision required the trial judge to consider patients, and not only hospitals, as victims of the crime."
The law is always more complex than a layman like me thinks, questions of standing, etc. But I would have simply assumed that the patients hurt and killed would naturally be counted among the victims and not just the organisations left out-of-pocket.
> And what level of risk is worth saving $1,450 per dose on an injection? 1/100? 1/1000?
I've have plenty of friends that would struggle to afford that. I have friends that buy black market drugs because they can't get/afford a prescription. I don't know if I would make the same choice but I can I can understand why some people do.
The reason people get endophthalmitis is rarely due to a contaminated batch, but it certainly happens. But frankly it’s unsustainable to have all patients on branded drug, it would be too costly for patients and payers. Not to mention it is slightly unethical in the US due to drug rebates incentivizing branded drug use.
Endophthalmitis is bad, but we can treat it if caught promptly. Patient education, informed consent, good hygiene practices, and easy access to their ophthalmologist can make a tremendous difference.
> But frankly it’s unsustainable to have all patients on branded drug, it would be too costly for patients and payers.
This is incorrect, the Canadian healthcare system negotiates drug costing at a per province rather than per patient manner and has managed to negotiate down drugs pretty significantly especially in Ontario. A national drug plan doesn't currently exist but it's likely that drug and dental coverage is going to be a goal in the near term.
In the US there is also a complex drug reimbursement program run by most manufacturers to offer rebates to patients in the form of trial cards or direct refunds that does help widen accessibility but those programs are generally limited to patients on private insurance due to the nature of incentives and, well, greed.
I think it's very fair to say "Within this current system brand name drugs are a ridiculous ask for most patients due to the availability of generic alternatives" but the system itself is deeply broken. Generics are sometimes whitelabeled versions of the same product but often what are considered inactive ingredients may be modified significantly from brand name versions leading to issues, especially when it comes to neurological drugs, of drastically different effects to patients. The brand name vs. generic problem is a lot more complex than most people give it credit for and while patients should always prefer generics when they're similarly functional there are very notable scenarios where they are not equivalent for treatment. This comment shouldn't be read in direct opposition to the full comment above as this drug is outside my wheelhouse but rather as a comment on generics in general.
Source: I work in a company that analyzes drug pricing and, more generally, comparative insurance reimbursement for a living.
The higher manufacturer price of the eyeball-safe formulation is clearly justified, then, i.m.o. Also, is it the doctor's responsibility to assume risk to save the patient money?
Assuming the compounding process is inherently more at risk of contamination. It also gets complicated when the extreme prices are involved: what risk of infection balances out with the risk that the patient will not be treated due to cost or will suffer whatever negative consequences due to bearing the cost? One in two? Probably not. One in a billion? Probably.
Considering that the doctor was able to test the batches and verify contamination, it seems like this is an important step that was skipped by the pharmacy.
My quick searching is showing that bevacizumab is the full antibody, but lucentis (ranibizumab) is just the fab. So, very similar, but indeed not the same thing. I would generally expect them to have the same effect, but biology is full of surprises.
They are not transforming the drug just the form. For example, elderly patients may have a hard time swallowing pills, for some medicines (not all) a compounding pharmacy can turn the pill into a lollipop. They can also turn things into like a cream or lotion.
/use to write code for a small independent pharmacy that had a couple compounding labs
Just went down a chatgpt rabbit hole because I was also curious - seems it’s literally physical repackaging, no modification of the drug itself- as another commenter pointed out it’s not quite the same molecule but they have the same effect? Someone correct me if I’m wrong
> How does a lowly pharmacy transform a drug that is not for eye injection into one that is?
New research probably discovered new applications for their product. Investors agree to diversify. Company developed a system to inject it. The system was approved by government agency at charge of this, and they give the green light to put it in the market.
This is totally normal. See Ozempic history.
The price of a treatment reflects also the collateral risks and probability to be sued for the physician and the company. The problem is not that it cost 1000 dollars, the real problem is that US government should be subsiding at least a part of this cost. Tax money is collected exactly for cases like this. The problem is that they are instead burning 14 millions to paint a pool in "American Idiot Green" dye and nobody says, this bill must be wrong. What they used to paint this? titanium?
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.
It's worse than this. Their cap is 80% of the Insurer's profit. Not the Insurer's Parent company. So often the parent company will own the Insurer as a subsidiary and own the Pharmacy, Hospital, Healthcare etc under the parent company.
This way as costs go up, it's really just bypassing the 80%. Because the hospital can charge the insurance subsidary X amount, and then the hospital profits to the parent company.
There needs to be a law in the US that health insurance organizations cannot be owned by anyone who owns a healthcare provider. Nor can the insurance company own healthcare providers.
I tried to explain to people in The Netherlands this exact problem when they were thinking about switching from single-player to a commercial insurance company model.
Insurance companies always have an incentive to make healthcare services expensive. They have even more incentive to make healthcare expensive and do deals on the backside where their suppliers give them a kickback. Even better if said kickback comes via a side door.
So we went for the commercial insurance companies. It took them 4 years before they change the drug choice from decentralised (Pharmacies deal with drugs companies, received small discounts which funded a good quality of care) to centralised (Insurance deal with drug companies, receives kickbacks) and the Pharmacies funding was drastically cut leading to worse quality of care and more drugs being used. Double-whammy because in the previous system the Pharmacy did medication reviews which almost always result in a reduction in drugs (the thing with drugs is that quite a lot of them are given to reduce side effects of other drugs, the original drug gets cancelled but the side effect reducer gets forgotten and just continues ad infinitum).
Health insurance has been super inflationary since then when controlled for quality of care.
> So, no, paradoxically, it is not in the interest of people paying for the treatment to save money. Quite the opposite.
I'll assume they're on company insurance. Which is often "self-insured" in that the company actually foots the bill as opposed to the insurance company.
Why don't corporations just drop insurance companies that decide to not allow cheaper medicines?
Large swaths of US insurance are underwritten by employers, with the insurance companies acting as contracted administrators. Employers don't have the incentives you list.
Why is there a continuous stream of healthcare providers threatening to or becoming out of network for various managed care organizations because they cannot come to an agreement on healthcare prices?
What’s so interesting about this that I just learned after googling about Spravato that ketamine is a treatment for serious depression. Why? That’s fascinating! Is it the dissociative effects?
A significant effect is through opioid receptor activation, as demonstrated by Williams et al. <https://doi.org/10.1038/s41380-019-0503-4> by blocking the receptor with naltrexone, which attenuated the antisuicidality effects.
The FDA's policy for the last couple of decades is that mixtures of mirror images will not get FDA approval unless there is a strong rationale for it.
Racemic mixture of ketamine was approved decades ago. If you want a new indication for ketamine, you will need to get approval for a single mirror image, as the FDA won't approve the old drug.
They did this because there are numerous examples of racemic mixture drugs having increased side effects from the less active mirror image, so the FDA decided no more racemic approvals.
My guess is your insurer would be happy to pay for the old version, but your doctor is heavily incentivized to use the new version as the markup on the drug is much, much higher.
>but your doctor is heavily incentivized to use the new version as the markup on the drug is much, much higher.
I don't think it is normal/usual for doctors to receive any benefits or profits from which drugs they prescribe. Other than golf outings with the drug company reps? Is there something I'm missing?
> Ketamine is made up of mirror image molecules and esketamine is the right-handed molecule.
Esketamine is their cutesy way of saying the word s-ketamine. The s- comes from the Latin word "sinister" which means this is the left-handed enantiomer, not the right-handed one.
It is stupidly expensive, given how generic ketamine itself is. In our case, sleep apnea treatment proved to be a much better option than that drug, as it was just hiding an underlying condition and the treatments only last for maybe a week or two anyway.
I think there have been some people using ketamine off-label, but I don't know much about that. It does need to be tightly controlled because it can cause breakthrough psychosis in some patients. They try to screen those out, but that's not as effective as one might hope given my experience of seeing that fail. And it that was very nearly a fatal mistake.
universal health care can be offered even in 3rd world countries but they're really smart about keeping costs low. they drastically cut the costs of medical service by just offering one or two generic drugs bbought in bulk from china and india rather than all those custom expensive drugs that do the same thing. it does the same thing but at a much lower cost
I tried health-tech twice. Opted out both times as there are too many misaligned incentives and useless rent-takers supported by Congress and other entrenched players.
At this point maybe the best solution is door to door doctors using AI.
I feel like the best way to fight this, if I was the government, would be to stop enforcing laws preventing patients and even doctors or hospitals from importing the overpriced pharmaceuticals from overseas generics manufacturers. Like the article points out, each pill costs no more than $0.25 to make. The goal wouldn't necessarily be to get everyone using overseas suppliers but to put downward pressure on the price gougers in the country.
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.
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).
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.
On paper you are right. You can file an NDA. But in reality you can't prove that the product on the market (the drug you are adding an NDA to) is sufficiently under your control to enable you to claim that it is safe and effective. Only a manufacturer can control the product. If you want to piggyback on top of an existing product in the market, you have to become a manufacturer or sign a contract with an existing one.
You are absolutely right about the incentives. There are absolutely none except to help humanity which is why only hospitals and universities are doing these off label studies.
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.
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.
Yes, but it's really tough. I read that 50% of Stanford Medical School budget comes from Big Pharma. It's really hard to get the message out. I believe Pharma (the biggest advertiser on Google) is influencing Google search results, among other things.
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
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?
>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.
We know they do because before the government took over the job, the nascent medicine industry would sell you literal poison.
In fact, you can see today what an unregulated pharmaceutical industry looks like. It's the supplements aisle at your local supermarket. The place where you can buy literal homeopathy sugar pills, and various completely unstudied compounds and other scams. You can buy turmeric for hundreds of dollars a pound.
If private industry was better than the government at managing drugs, the American supplements industry would mean we should have dramatically better health outcomes and dramatically cheaper healthcare
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.
"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.
This is completely backwards read Marx. Superstructure (culture, politics) flows from the economic base (there are some important exceptions, but that’s the dominant arrow).
I have a little insight here from working with ophthalmologists.
When the article mentions "using a cancer drug to treat a leading cause of blindness" it's talking about using Bevacizumab (brand name Avastin) to treat macular degeneration.
Avastin and Lucentis are molecularly the same drug. The difference is that Avastin isn't packaged to be injected into eyeballs, and Lucentis is. Also, Avastin costs about $50/dose, and Lucentis costs around $1,500/dose.
There are compounding pharmacies that will repackage Avastin into a format that can be injected into eyeballs.
However, many ophthalmologists are hesitatnt to use Avastin because that process introduces the potential for contamination. Not that it happens frequently, but every ophthalmologist I know lives in fear of introducing an infection into their patient's eyeballs. And what level of risk is worth saving $1,450 per dose on an injection? 1/100? 1/1000?
I know at least one ophthalmologist who would use Avastin, but would culture a sample from every batch she got from the compounding pharmacy, and had at least one batch that cultured bacteria.
Assumedly, if she hadn't, every patient she injected with that batch would have been at risk of contracting endophthalmitis, and endophthalmitis is no joke. Not infrequently, it can mean losing vision.
I know several of that ophthalmologist's colleagues who had been using compounded Avastin to try and save their patients money, stopped after that incident.
I don't really have a conclusion beyond "drug pricing is insane and the issue is complex for providers."
Compounding pharmacies can get injectibles wrong in a deadly way. Many families are still waiting for justice after the MECC pharmacy caused the deaths of 64 people:
https://en.wikipedia.org/wiki/New_England_Compounding_Center...
This note in that WP link is wild:
"On July 7, 2021, Barry Cadden's original 9-year sentence was increased to 14.5 years. An appeals court court decision required the trial judge to consider patients, and not only hospitals, as victims of the crime."
The law is always more complex than a layman like me thinks, questions of standing, etc. But I would have simply assumed that the patients hurt and killed would naturally be counted among the victims and not just the organisations left out-of-pocket.
> And what level of risk is worth saving $1,450 per dose on an injection? 1/100? 1/1000?
I've have plenty of friends that would struggle to afford that. I have friends that buy black market drugs because they can't get/afford a prescription. I don't know if I would make the same choice but I can I can understand why some people do.
The reason people get endophthalmitis is rarely due to a contaminated batch, but it certainly happens. But frankly it’s unsustainable to have all patients on branded drug, it would be too costly for patients and payers. Not to mention it is slightly unethical in the US due to drug rebates incentivizing branded drug use.
Endophthalmitis is bad, but we can treat it if caught promptly. Patient education, informed consent, good hygiene practices, and easy access to their ophthalmologist can make a tremendous difference.
Source: I do these injections for a living.
> But frankly it’s unsustainable to have all patients on branded drug, it would be too costly for patients and payers.
This is incorrect, the Canadian healthcare system negotiates drug costing at a per province rather than per patient manner and has managed to negotiate down drugs pretty significantly especially in Ontario. A national drug plan doesn't currently exist but it's likely that drug and dental coverage is going to be a goal in the near term.
In the US there is also a complex drug reimbursement program run by most manufacturers to offer rebates to patients in the form of trial cards or direct refunds that does help widen accessibility but those programs are generally limited to patients on private insurance due to the nature of incentives and, well, greed.
I think it's very fair to say "Within this current system brand name drugs are a ridiculous ask for most patients due to the availability of generic alternatives" but the system itself is deeply broken. Generics are sometimes whitelabeled versions of the same product but often what are considered inactive ingredients may be modified significantly from brand name versions leading to issues, especially when it comes to neurological drugs, of drastically different effects to patients. The brand name vs. generic problem is a lot more complex than most people give it credit for and while patients should always prefer generics when they're similarly functional there are very notable scenarios where they are not equivalent for treatment. This comment shouldn't be read in direct opposition to the full comment above as this drug is outside my wheelhouse but rather as a comment on generics in general.
Source: I work in a company that analyzes drug pricing and, more generally, comparative insurance reimbursement for a living.
The higher manufacturer price of the eyeball-safe formulation is clearly justified, then, i.m.o. Also, is it the doctor's responsibility to assume risk to save the patient money?
Assuming the compounding process is inherently more at risk of contamination. It also gets complicated when the extreme prices are involved: what risk of infection balances out with the risk that the patient will not be treated due to cost or will suffer whatever negative consequences due to bearing the cost? One in two? Probably not. One in a billion? Probably.
Considering that the doctor was able to test the batches and verify contamination, it seems like this is an important step that was skipped by the pharmacy.
How does that justify a 30 fold increase?
If an individual Dr can get a batch checked while saving the patient money, it obviously isn't justified.
They have similar targeting but are not the same molecule.
My quick searching is showing that bevacizumab is the full antibody, but lucentis (ranibizumab) is just the fab. So, very similar, but indeed not the same thing. I would generally expect them to have the same effect, but biology is full of surprises.
How does a lowly pharmacy transform a drug that is not for eye injection into one that is?
They are not transforming the drug just the form. For example, elderly patients may have a hard time swallowing pills, for some medicines (not all) a compounding pharmacy can turn the pill into a lollipop. They can also turn things into like a cream or lotion.
/use to write code for a small independent pharmacy that had a couple compounding labs
Just went down a chatgpt rabbit hole because I was also curious - seems it’s literally physical repackaging, no modification of the drug itself- as another commenter pointed out it’s not quite the same molecule but they have the same effect? Someone correct me if I’m wrong
E.g., by physically crushing up tablets and dissolving them in a solution.
> How does a lowly pharmacy transform a drug that is not for eye injection into one that is?
New research probably discovered new applications for their product. Investors agree to diversify. Company developed a system to inject it. The system was approved by government agency at charge of this, and they give the green light to put it in the market.
This is totally normal. See Ozempic history.
The price of a treatment reflects also the collateral risks and probability to be sued for the physician and the company. The problem is not that it cost 1000 dollars, the real problem is that US government should be subsiding at least a part of this cost. Tax money is collected exactly for cases like this. The problem is that they are instead burning 14 millions to paint a pool in "American Idiot Green" dye and nobody says, this bill must be wrong. What they used to paint this? titanium?
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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.
It's worse than this. Their cap is 80% of the Insurer's profit. Not the Insurer's Parent company. So often the parent company will own the Insurer as a subsidiary and own the Pharmacy, Hospital, Healthcare etc under the parent company.
This way as costs go up, it's really just bypassing the 80%. Because the hospital can charge the insurance subsidary X amount, and then the hospital profits to the parent company.
There needs to be a law in the US that health insurance organizations cannot be owned by anyone who owns a healthcare provider. Nor can the insurance company own healthcare providers.
We've allows the Ma Bell of healthcare to exist.
I tried to explain to people in The Netherlands this exact problem when they were thinking about switching from single-player to a commercial insurance company model.
Insurance companies always have an incentive to make healthcare services expensive. They have even more incentive to make healthcare expensive and do deals on the backside where their suppliers give them a kickback. Even better if said kickback comes via a side door.
So we went for the commercial insurance companies. It took them 4 years before they change the drug choice from decentralised (Pharmacies deal with drugs companies, received small discounts which funded a good quality of care) to centralised (Insurance deal with drug companies, receives kickbacks) and the Pharmacies funding was drastically cut leading to worse quality of care and more drugs being used. Double-whammy because in the previous system the Pharmacy did medication reviews which almost always result in a reduction in drugs (the thing with drugs is that quite a lot of them are given to reduce side effects of other drugs, the original drug gets cancelled but the side effect reducer gets forgotten and just continues ad infinitum).
Health insurance has been super inflationary since then when controlled for quality of care.
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> So, no, paradoxically, it is not in the interest of people paying for the treatment to save money. Quite the opposite.
I'll assume they're on company insurance. Which is often "self-insured" in that the company actually foots the bill as opposed to the insurance company.
Why don't corporations just drop insurance companies that decide to not allow cheaper medicines?
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Large swaths of US insurance are underwritten by employers, with the insurance companies acting as contracted administrators. Employers don't have the incentives you list.
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They operate with similar supply and demand constraints and competition, even with prices increasing
>Insurance companies do not want cheaper care.
Why is there a continuous stream of healthcare providers threatening to or becoming out of network for various managed care organizations because they cannot come to an agreement on healthcare prices?
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We baked the snake charmer problem into the law?
Good lord.
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What’s so interesting about this that I just learned after googling about Spravato that ketamine is a treatment for serious depression. Why? That’s fascinating! Is it the dissociative effects?
A significant effect is through opioid receptor activation, as demonstrated by Williams et al. <https://doi.org/10.1038/s41380-019-0503-4> by blocking the receptor with naltrexone, which attenuated the antisuicidality effects.
The Huberman Lab episode Ketamine: Benefits and Risks for Depression, PTSD & Neuroplasticity <https://www.hubermanlab.com/episode/ketamine-benefits-and-ri...> and the referenced journal articles (including the above) have a lot of detail on it.
Blame the FDA on that one.
The FDA's policy for the last couple of decades is that mixtures of mirror images will not get FDA approval unless there is a strong rationale for it.
Racemic mixture of ketamine was approved decades ago. If you want a new indication for ketamine, you will need to get approval for a single mirror image, as the FDA won't approve the old drug.
They did this because there are numerous examples of racemic mixture drugs having increased side effects from the less active mirror image, so the FDA decided no more racemic approvals.
My guess is your insurer would be happy to pay for the old version, but your doctor is heavily incentivized to use the new version as the markup on the drug is much, much higher.
Thalidomide being one of the more notable ones (though apparently neither chirality is truly safe)
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>but your doctor is heavily incentivized to use the new version as the markup on the drug is much, much higher.
I don't think it is normal/usual for doctors to receive any benefits or profits from which drugs they prescribe. Other than golf outings with the drug company reps? Is there something I'm missing?
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The NHS in the UK refuses to cover it in part because of the absurd cost.
So in Ketamine approved as a treatment in other countries but not in the US?
> Ketamine is made up of mirror image molecules and esketamine is the right-handed molecule.
Esketamine is their cutesy way of saying the word s-ketamine. The s- comes from the Latin word "sinister" which means this is the left-handed enantiomer, not the right-handed one.
It is stupidly expensive, given how generic ketamine itself is. In our case, sleep apnea treatment proved to be a much better option than that drug, as it was just hiding an underlying condition and the treatments only last for maybe a week or two anyway.
I think there have been some people using ketamine off-label, but I don't know much about that. It does need to be tightly controlled because it can cause breakthrough psychosis in some patients. They try to screen those out, but that's not as effective as one might hope given my experience of seeing that fail. And it that was very nearly a fatal mistake.
universal health care can be offered even in 3rd world countries but they're really smart about keeping costs low. they drastically cut the costs of medical service by just offering one or two generic drugs bbought in bulk from china and india rather than all those custom expensive drugs that do the same thing. it does the same thing but at a much lower cost
Related, one of my all time favorite articles: https://www.propublica.org/article/revlimid-price-cancer-cel...
I tried health-tech twice. Opted out both times as there are too many misaligned incentives and useless rent-takers supported by Congress and other entrenched players.
At this point maybe the best solution is door to door doctors using AI.
This was so hurtful and blood boiling to read. How is stuff like this allowed to happen?
The system is broken. Hence Luigi.
lack of disincentives to do this
Thank you, really liked this one.
The Price of Remission - https://news.ycombinator.com/item?id=43925396 - May 2025 (93 comments)
This was a good read, thanks for sharing.
I feel like the best way to fight this, if I was the government, would be to stop enforcing laws preventing patients and even doctors or hospitals from importing the overpriced pharmaceuticals from overseas generics manufacturers. Like the article points out, each pill costs no more than $0.25 to make. The goal wouldn't necessarily be to get everyone using overseas suppliers but to put downward pressure on the price gougers in the country.
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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.
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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).
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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.
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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.
On paper you are right. You can file an NDA. But in reality you can't prove that the product on the market (the drug you are adding an NDA to) is sufficiently under your control to enable you to claim that it is safe and effective. Only a manufacturer can control the product. If you want to piggyback on top of an existing product in the market, you have to become a manufacturer or sign a contract with an existing one.
You are absolutely right about the incentives. There are absolutely none except to help humanity which is why only hospitals and universities are doing these off label studies.
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.
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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
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.
Yes, but it's really tough. I read that 50% of Stanford Medical School budget comes from Big Pharma. It's really hard to get the message out. I believe Pharma (the biggest advertiser on Google) is influencing Google search results, among other things.
Here is a site that focuses on COVID and Cancer: https://imahealth.org/
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
What is repurposing drugs?
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.
All the same problems exist in corporations. That disconnected idiocy is a function of size, not government vs private.
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?
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>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.
We know they do because before the government took over the job, the nascent medicine industry would sell you literal poison.
In fact, you can see today what an unregulated pharmaceutical industry looks like. It's the supplements aisle at your local supermarket. The place where you can buy literal homeopathy sugar pills, and various completely unstudied compounds and other scams. You can buy turmeric for hundreds of dollars a pound.
If private industry was better than the government at managing drugs, the American supplements industry would mean we should have dramatically better health outcomes and dramatically cheaper healthcare
Neither are true.
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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/
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.
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.
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"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.
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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.
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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.
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The US is not a capitalist society, it is a liberal society. Capitalism is a consequence of that but it isn't the reason.
This is completely backwards read Marx. Superstructure (culture, politics) flows from the economic base (there are some important exceptions, but that’s the dominant arrow).
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