FDA approves intranasal esketamine formulation
nytimes.com
nytimes.com
Let's say my doctor says to me "you're depressed, I'm prescribing esketamine, go to this clinic and pay them $3000". Well, I do my research and learn that really this stuff has the same antidepressants effect as ketamine. And the same number of doses of ket on the darknet markets are going to cost me a heck of a lot less.
Sure, there's the question of legality. But if I can't afford esketamine but can afford dodgy internet ket, and I'm desperate for something, anything, to help with this nagging constant psychic pain weighing down my life...
Suddenly I appreciate my Canadian single payer health care system a lot more, even with the small problems it has.
On a risk/harm scale, it's comparable to alcohol or cigarettes[1].
[1]: https://en.wikipedia.org/wiki/Drug_harmfulness#/media/File:D...
When you get ketamine from the internet, you're getting a mystery powder that is, at best, a potent form of an addictive drug in quantities that are not metered and are ripe for abuse. At worst, you're getting some form of fentanyl because internet drug dealers are inept.
> a potent form of an addictive drug
It's literally the same chemical; you didn't use those adjectives when you described it earlier.
> quantities that are not metered
Readily fixed for < $20: https://www.amazon.com/dp/B07D1NNGM6/
https://erowid.org/chemicals/ketamine/ketamine_dose.shtml#or...
> At worst, you're getting some form of fentanyl because internet drug dealers are inept.
That's not a ketamine problem; it's a prohibition problem.
My friend had one like this. It was barely accurate enough for all the funny RCs we had.
I would talk the same way about treating ADHD with Desoxyn prescribed by a doctor versus buying a pile of methamphetamine online to self-medicate with.
> Readily fixed for < $20: https://www.amazon.com/dp/B07D1NNGM6/
If you're going to make bad choices, volumetric dosing is one of the less bad choices.
> That's not a ketamine problem; it's a prohibition problem.
It's a regulation problem. The supplement market is full of bunk or outright fake products. It took the FDA to reel actual medicine in.
At least near me, there are "ketamine centers" that already to ketamine clinics - $500 per session, and insurance doesn't cover it. Ends up being around $3000. I haven't done it, so I can't comment on its effectiveness.
It's pretty lame that the cost difference is so large. I guess the barrier is a psychiatrist's willingness to prescribe. Maybe all of this research will open up psychiatrists to prescribe take-home ketamine more readily?
It's been a long time since I lived in Canada, but one of the "small problems" was that prescription medicine wasn't covered. You need private health insurance, or you need to be covered by one of many confusing provincial health care plans. Generally, you can find a way, but at least 15 years ago (when I left) it could be pretty dicey. I remember several of my friends having difficulty affording their insulin when I was in university -- too rich to qualify for aide, too poor to be able to pay for their life saving drugs without hardship. My dad (who still lives there) tells me things have improved, but he still pays more for prescription drugs than I do (living in Japan) I think.
The UK's NHS seems to be a better system to compare to ;-) I lived there for 2 years and was really surprised at what the NHS covers. Interestingly they will even pay for emergency treatment for non-residents who happen to be in the country!
The caveat is all of the stuff that the NHS won't cover. The service is largely free at the point of use, but there has always been some element of rationing which has drastically increased in recent years due to Conservative government cuts.
Mental health gets the short end of the stick in this respect - it represents 23% of the disease burden but only 13% of NHS spending. Most patients with a mental health condition will never see a psychiatrist and receive no more than six half-hour sessions of psychotherapy. If esketamine does prove to be effective, the NHS is exceedingly unlikely to offer it to more than a handful of patients until the patent expires.
https://www.nuffieldtrust.org.uk/resource/rationing-in-the-n...
[1] https://www.nhs.uk/using-the-nhs/nhs-services/visiting-or-mo...
In the specific case of ketamine for depression, some people do seem to have successfully gotten insurance companies to pay for it.[2] Even without FDA approval, this would probably get easier over time, as more studies show effectiveness.
[1] https://www.aafp.org/afp/2003/0801/p498.html [2] https://www.ketaminewellnesscenters.com/getting-insurance-to...
is just a system that forces healthy people to pay for unhealthy people.
In this last case, you might pay more for certain markers (smoking, uncontrolled high blood pressure, and other wellness marks), but not if you have asthma or migraines, for example. Part of your premium is literally paying for folks that are sick. Paying for other people's pregnancies and children and stuff like that.
[1] https://en.wikipedia.org/wiki/List_of_countries_by_total_hea...
My DIY nasal spray is made from liquid ketamine vials purchased off the dark net. The vials are 1g in 10ml saline and are intended for veterinary use. They come factory sealed with holographic labeling, and I'm confident they are legit. They cost $100-$150 each which is a lot more than powder but I am much more confident in what I'm getting and it's already in liquid form. I use a needle to extract the ketamine from the vial and put it into an amber glass nasal spray bottle after sterilizing it. The solution is already isotonic, no need to add any salt.
I'll do a squirt on each side of my nose against the nasal wall when I'm really depressed / suicidal, which is usually no more than once a month. It's not magic, but it really brings me back to reality about half the time.
I have also tried an IV ketamine clinic, paid about $3k to go 3 times. Unfortunately that is super expensive and the last time I had what amounted to a bad trip and I haven't been back.
If anyone has any questions about these I'm happy to answer them.
To anyone feeling depressed: If you haven't done so already, get the basics out of the way: Get a physical and get your thyroid levels checked. Consider supplementing vitamin D, fish oil, and magnesium. You can find academic evidence that those may help in people who are deficient.
The price of $3k for 8 doses is so high compared to regular ketamine. I wonder if there is any real difference or if you’re really just paying for the comfort of doing it legally under the guidance of a doctor.
You're really paying for the cost of bringing a new drug to market for a specific label use. It wouldn't be worth the multi-million dollar expense for any for-profit company to do the FDA process to show that ordinary ketamine is effective for depression, because they couldn't privatize the profits to recoup their costs.
Instead they make an arbitrary but likely nonfunctional[0] chemical change[1], get it approved, and use their patent to demand high costs to recoup their FDA process fees (and if they're lucky, to make a profit).
[0]: Edit/clarification: Apparently some (meta)studies suggest the S-isomer is better than the racemic mixtures in some ways (waving my hands; I did not read or understand the details).
[1]: Edit/clarification: I don't know enough chemistry to be sure if describing the extraction of the S-isomer from the racemic mixture is a "chemical change," exactly, but you get the idea.
The trouble for anyone (citizens, government, and biotech companies) is sifting the wheat from the chaff as far as what drugs are likely to be safe and effective treatments. You could give away all of your money and not end up with one approved drug.
Edit: It's a common delusion that pharmaceuticals are sold for therapeutic uses. Actually, they're a mechanism to monetize intellectual property.
Edit: Oops. For having just the active isomer.
Edit: That comment about monetizing intellectual property comes from an expert economist :)
And just because it’s present in a plant doesn’t mean it can be drugged. It could have a short half life, high toxicity, etc., so derivatives are made to optimize it’s action.
Finally, even if a patent can’t be secured, the first version of a drug is given exclusivity by the FDA - they won’t approve another version up to 7 years (orphan drugs).
A cursory look at the top selling drugs of all time doesn't appear to show any plant derived drugs [0]. Obviously this does not disprove your statement but its the quickest heuristic i could think of
[0] https://en.wikipedia.org/wiki/List_of_largest_selling_pharma...
OP's statement was about sheer number of patented drugs. I don't know that OP's statement was accurate, but the wikipedia link doesn't really refute or confirm the idea.
[1] "pharmaceutical and biotechnology sales revenue increased from $534 billion to $775 billion between 2006 and 2015.... Drug industry spending for research and development increased from $82 billion in 2008 to $89 billion in 2014" (I assume there are other costs so one cannot simply divide to get gross profit but it seems illustrative)
In 2018 only like 12% of new FDA approved drugs were developed by big pharma. 63% were developed by small companies. A negligible amount were discovered by universities alone
Pharma acquired these drugs from startups through M&A which doesn't show up in profit and loss statements. It shows up on the balance sheet
That $84B r&d figure seems very low. The top 15 pharma companies spend something like $75B a year in r&d. VC backed startups spend like $10-15B. Then all the firms in between account for the majority of spending. Don't remember the source but I think total global pharma r&d is like $200B
https://www.nytimes.com/2014/11/19/upshot/calculating-the-re...
In 2018 only like 12% of new FDA approved drugs were developed by big pharma. 63% were developed by small companies. A negligible amount / zero were developed by universities
The $161M figure cited in that nytimes study is not at all representative because most early stage r&d is done outside of big pharma, and then big pharma buys the drugs and markets them
If drug research was profitable pharma would be doing more of it, not less
But maybe there's also a patent on the delivery mechansim. Or maybe it's a process patent.
Janssen obviously believes that it's valid. Or at least, they're confident that they can defend it. Maybe they know that it's not valid, but are confident that others won't figure out why.
In one case that I recall, the manufacturer bribed a chemist to retract a paper that had reported the synthesis of their drug.
Many years of budget cuts have rendered the Patent Office pretty clueless about drugs. And the FDA doesn't do any independent assessment of patent validity. I've seen testimony where FDA staff said that they lack expertise for that.
So basically, patents are valid if they survive litigation.
Anybody could perform a sufficiently capable of job this has way better career opportunities than earning $80k at the patent office. While this does support your notion of budgetary cuts being the primary problem, again I think that misses the core problem which is that the system has become so convoluted that actually having a meaningful holistic understanding requires immense skill and education. Systems that are supposed to be for public, and individual, use should not require a juris doctor to begin to parse.
The whole system needs a major overhaul, frankly like much of our formal structures. Isn't it a bizarre system that people are expected to completely obey laws which they are in no way expected to be able to completely understand?
> "A person shall be entitled to a patent unless . . . the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention."[0]
0) https://www.whitecase.com/publications/alert/supreme-court-s...
But if S(+) ketamine has been commercially available, even if only illegally, it's not patentable.
How could they recoup those costs without IP protection?
[1] https://clinicaltrials.gov/ct2/results?cond=&term=Esketamine...
So the next version will be monetizing the delivery system.
Clinical benefit -- making sick patients healthier -- creates value
You need patents because without patent protection, no one would invest the large sums of money and take on the huge risk to bring drugs to market
These days, investors and companies generally only fund development of drugs that provide a significant clinical benefit to really sick patients. This is because they deeply understand that value in pharma is determined by clinical benefit
The statement that pharmaceuticals are not sold for therapeutic uses is just wrong.
That's just semantic hand waiving.
Patents create value. With no patent, as with generic drugs, price approaches marginal cost of production. With a patent, price is limited only by competition with other therapies. And sometimes by regulatory intervention.
> These days, investors and companies generally only fund development of drugs that provide a significant clinical benefit to really sick patients. This is because they deeply understand that value in pharma is determined by clinical benefit
That's because "really sick patients" are desperate.
Right. But the thing is, bringing a drug to market is extremely expensive. So without patents, there isn't a financial incentive to bring a drug to market. Biotech companies aren't charities.
> That's because "really sick patients" are desperate.
Not sure what you're driving at. The alternative to offering an extremely expensive patented drug to really sick patients is no drug at all (or whatever the previous standard of care was). Yeah, drugs are expensive until the patent runs out, but the patent does eventually run out.
Without this system, we wouldn't have new drugs brought to market by for-profit companies. With this system, sure, new drugs are really expensive the first 17-20 years. But then they're really inexpensive, and exist. In the other timeline, they simply did not exist.
However, I am arguing against patent protection for de minimis structural changes that have no substantial therapeutic benefit. Or bullshit delivery systems.
For example, I use testosterone creme. Androgel costs a bloody fortune, because their formulation (basically hair gel) has patent protection. So I use a compounded cream that costs ~90% less.
> The alternative to offering an extremely expensive patented drug to really sick patients is no drug at all (or whatever the previous standard of care was).
That's not the only alternative. Drug development ought to be publicly funded. As it is, the drug industry tends to leech off publicly-funded research. And drug manufacturers ought to be paid only for the manufacturing.
Potato, potato. If they don't do the work to get FDA approval, even with the bullshit de minimis change, the alternative isn't a patent-free generic — it's nothing, for any price.
> Androgel costs a bloody fortune, because their formulation (basically hair gel) has patent protection. So I use a compounded cream that costs ~90% less.
So what is the problem with androgel's patent? How does it make your life worse? If they didn't have the patent, you'd still be using the same previous standard-of-care.
> Drug development ought to be publicly funded.
Well, good luck with that.
> And drug manufacturers ought to be paid only for the manufacturing.
Like, at-cost? I think you'd see drug manufacturing die out under that proposed policy.
No, the alternative is some old generic drug, which is just as effective as the new one. But the manufacturer bribes doctors to prescribe the new one, which has no generic equivalents.
> So what is the problem with androgel's patent? How does it make your life worse?
Because for years there was no commercial alternative. It was only by chance that I found a compounding pharmacy that sold an old-school version.
> Like, at-cost? I think you'd see drug manufacturing die out under that proposed policy.
That's how it works for generics. And there are lots of generics.
This is a little simplistic. The FDA strongly prefers evidence that new drugs are more effective than existing treatments. They look at the target condition and available treatments, including existing generics, to weigh the benefits and risks of a new drug being approved.
And the only reason that "old generic" drug exists at all is because the patent process paid for its R&D more than 20 years ago.
> But the manufacturer bribes doctors to prescribe the new one, which has no generic equivalents.
This is illegal, for obvious reasons. I suspect it is less wide-spread than you think.
> Because for years there was no commercial alternative. It was only by chance that I found a compounding pharmacy that sold an old-school version.
So you're saying there wasn't an alternative treatment available and androgel brought an effective treatment to market and was rewarded for it? And they shouldn't be, because?
> That's how it works for generics. And there are lots of generics.
Generics manufacturers first, absolutely do not sell at-cost; they're for-profit companies trying to make money, not charities. And most importantly, they don't develop novel drugs.
I've seen many thousands of internal documents from pharmaceutical firms. It's ~all about the money.
Except the government.
They already fund virtually all basic research in the US (and the world). I don't understand why they couldn't start funding pharmaceutical R&D.
Plus 30% or so of NIH money goes to universities for "overhead" and not to research
The odds of a promising academic finding becoming a drug are incredibly low. and there is not enough NIH funding to support drug discovery and development
I also think that if drug research was publicly funded t would be a nightmare. You'd probably end up with drugs costing more than they do now (in terms of added taxes you'd have to pay to bolster NIH budget) and getting fewer drugs approved. Pharma r&d is actually held to a much higher standard in terms of robustness than academic science. The incentives are just messed up in academia -- people want to publish first and foremost, not make medicines. And you can get crappy / irreproducble science published fairly readily
One of the first things pharma companies do when considering licensing academic tech is try to replicate the findings independently. Often they can't
At least in pharma, the incentives are to make drugs that get FDA approval, that docs prescribe to patients and that insurance companies pay for. For all that to happen the drugs have to work and work very well. And even with the profit motive as an incentive there is still poor decision making and incentive alignment
some people are studying ketamine + some sort of therapy, but it isnt clear whether this actually works, who it may work for or what the ideal regimen is. the idea is that ketamine treatment provides a very rapid antidepressive effect, but that effect isnt durable after treatment stops. some forms of psychotherapy are more effective when people are only mildly depressed, so ketamine can "prime" people for psychotherapy
F.D.A. approval requires that doses be taken in a doctor’s office or clinic, with patients monitored for at least two hours… The safety monitoring will require doctors to find space for treated patients, which could present a logistical challenge, some psychiatrists said.
I can kill a few birds with one stone here. Doctors should offer the 2-hour sessions in the evening, in darkened "clinics" with dance floors and DJ music.
I heard about the approval on NPR, where they interviewed a doctor from Icahn school of medicine to talk about the benefits of such a formulation, without any mention of this patent. Is there any way to find out if J&J licensed their patent?
Edit: meant racemic instead of non racemic
https://www.drugs.com/history/spravato.html
https://www.drugs.com/alpha/sp.html [not listed yet]
The article reports the experiment, the results, and not only FDA approval.
Color me doubtful.
Stay away from calculus, kids.
He was a really good/unique/smart guy, though :/ He was also pretty staunchly atheist... Perhaps he needed to know, once and for all.
Because this is the US we're talking about, I've had to change doctors pretty frequently in my life and there are only a small handful I would say wouldn't react negatively. I'm pretty sure the proliferation of Epic has made it worse too.
Certainly something to be concerned about. I've read ketamine abusers can often end up with kidney issues (presumably proportional to dosage as its related to elimination), but I'd also think monitoring kidney health with chronic dosing, even at low levels, could be prudent - especially in individuals with pre-existing kidney issues.
It does not have to be the case. In some European countries it is ridiculously cheap, as cheap as any other basic/necessary medications, medications that are super expensive to the Americans.
However, years of experience have led me to believe that throwing drugs at this problem does nothing but mask some of the symptoms temporarily, while often having somewhat undesirable side effects. I think we just keep doing it because depression is not well understood, doctors (like the rest of us) are lazy and incentivized to get you out of their office as quickly as possible, and phrama is big business.
https://twitter.com/melaynalokosky/status/110311449708494028...
Most famously, it was used to sedate the boys trapped in the caves in Thailand last year (during their extraction).
The Maclean's story is the one that I first saw it in: https://www.macleans.ca/thai-cave-rescue-heroes/
https://www.smh.com.au/world/asia/we-didn-t-expect-all-13-ou...
When you give and bond with people, your body releases oxytocin. When you do cold showers, your body releases seretonin. When you laugh or meditate, your body releases endorphin. I can go on and on. All of which helps bring back balance to the mood and get people rid of depression.
You create a chemical/toxic & selfish society,where everything MUST be fixed through chemical drugs backed by greed of pharma companies that does half-dashed studies, you are doing humanity endless harm.
This is not depression.