Posted by giuliomagnifico 8 hours ago
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.
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...
Exciting stuff, if it gets FDA approved.
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.
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.
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.
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.
Changing the law will take time (election cycles). If you cannot leave the US for a developed country that won't squeeze to extract from you while you're trying to meet your healthcare needs, importing your drugs that can be imported without US approval is your only path in the short term, or potentially traveling to obtain them and bring them back (roughly two-thirds of the entire U.S. population, ~200M people, live within 100 miles of a U.S. land or coastal border).
(not legal advice, i am just an internet rando)
This means such studies can give more clarity on which off-label use is beneficial but it can't be an officially allowed usage.
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.
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.)
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.
This isn’t a new or novel concept. Doctors manage patients with off-label prescriptions all day long.
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.
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.
* --------- re: below due to throttling -------
>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.
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.
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.
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.
Doctors here are allowed to prescribe them though.
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.
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
https://www.drugpatentwatch.com/blog/patenting-new-uses-for-...
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
https://synapse.patsnap.com/blog/what-are-the-types-of-pharm...?
That's a lie, I get off-label drugs prescribed monthly covered.
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.
You can also search here: https://clinicaltrials.gov/
I was a clinical trial participant once and it was a positive experience for me.
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’.
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.
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 is a false dichotomy and this kind of zero sum thinking is exactly the root of so much misunderstanding of economics that's all the rage these days (and probably forever).
Wealth is created by innovation, not transfered. "Rent seeking" is wealth transfer but most companies provide a service that is more valuable than what exists without them.
The goal of capitalism is to allow the capitalist to increase their profits by improving the public good. "Public good" being measured by what people are willing to spend their money on. It isn't to increase the capatalists profits at all costs. The entire idea is built on exploiting the capitalist's impulse to increase profits to also serve the public good.
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.
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
> 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.
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?
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.
Because you are both absolutely right.
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.
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.
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.
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.
I’ll have to keep this in mind the next time it comes up…
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.
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.
If we had proper competition and price discovery, things would be much better.