> M4 and M1 receptor stimulation indirectly rebalances dopaminergic and glutamatergic circuits involved in the symptoms associated with neurological and neuropsychiatric diseases such as schizophrenia and Alzheimer's disease.
Whoa. Wonder if that's being evaluated?
Co-administration of an agonist and an antagonist for the same pharmacophore seems like an interesting approach.
Looks like the antagonist is only outside the brain, so it works to counteract the side-effects, pretty cool.
I wanted sort of the opposite of this for opioids - work in the body, not the brain. There's been a few attempts but non that passed trials.
Would the opposite (work in the brain but not the body) also be a healthier alternative for people addicted to getting high on opiates?
Yeah, because it is the high they are after, but not working in the brain would make opioids completely useless for depression and anxiety (for which it really does wonders).
look, if someone has actually have a new drug that works like antipsychotics but doesn't have the nightmare side effects, i am very happy for that person to get filthy rich.
if this pans out the way they hope, by all means give the lead guy a couple yachts or whatever he wants. space tourism, gold statue of himself, whatever. big bonuses all the way down the org chart.
there's the potential to reduce an absolutely staggering amount of human misery here. frankly (again if this pans out) our homelessness crisis would look very different if this drug had existed 20 years ago, when the mechanism of action was discovered.
the people who cared enough and took a huge concentrated risk to do this should just get rich, if in fact it pans out.
> a price in line with expected clinical benefits to patients
What would a price in line with recouping R&D and production costs and, say, a 20% profit margin be?
Bristol Myers Squibb acquired Karuna Therapeutics, the company behind Cobenfy (formerly KarXT), for $14 billion earlier this year so that’s their break even for the drug and presumably what their investors thought was fair. I don’t think Karuna had anything else interesting in trials so they have to recoup all of that from Cobenfy before they’re in the black on the acquisition.
Pharmaceutical companies offload most of the risk onto institutional investors and the public (most biotechs IPO pre-revenue to fund clinical trials) but the flipside is that they have to pay eye-watering sums to acquire promising drugs.
In their last 10-K, Bristol Myers Squibb reported an operating income of $8.4bn on sales of $43.7bn, giving them a gross profit margin of just over 19%.
https://www.sec.gov/ix?doc=/Archives/edgar/data/14272/000001...
It may not be fair math. The company may bet on 10 different things and just one pays off. It needs to pay off for the bad bets as well.
> in line with recouping R&D and production costs
That's the "recouping R&D" part.
You shouldn't look at R&D on one product, since lots fail. Would be like saying a record label that funds 100 artists with 1 being profitable should have a strict 20% profit cap on the profitable one. That wouldn't allow ongoing funding of the broader pool of bets.
How much of the record label's music production is funded by tax dollars?
Per wikipedia, wholesale for the drug is $1,850/month.
I think I echo my prior comments on the US health and pharma system: why?
[0] https://en.wikipedia.org/wiki/Xanomeline/trospium_chloride
Let's remember it was recently proven that there is little to no evidence that serotonin levels are linked to depression: https://www.nature.com/articles/s41380-022-01661-0
It's pretty much likely to be the same deal here.
Since there is no chemical or biological test one can do to confirm a schizophrenia diagnosis, it's a subjective diagnosis by practitioners, treating such subjective diagnosis with powerful brain-chemistry altering drugs. Worse, we do not yet know whether these new drugs will be easy to get off of. Some of the other anti-psychotic type medication is VERY hard to get off of, such as abilify, where most drug treatment centers will not deal with Abilify withdrawals or take on those patients because those are so severe (extreme violence, self harm, etc during withdrawal).
Until Psychiatry can reform itself to become a real science, using the scientific method (repeatable, provable results and not just a "theory of how brain chemistry maybe works sorta but we're not sure"), it will continue to just be a big cash cow for Big Pharma while hooking many patients who do not need these drugs onto them for life, while failing to effect ANY cure on the things they are treating (Have you heard of someone getting "better" after taking anti-depressants and being able to come off them? No. They have to take them for life. That's not a cure.)
This is so misguided that it's hard to even know where to begin. People who develop high blood pressure without a known underlying cause take a pill for it every day for the rest of their life. You could say the same thing, they're not cured, but what actually matters is that they get to live a full life, unconstrained by the disease even if we don't know the underlying cause. Of course it would be better if we were more advanced of a civilization and figured it out, but the important thing is that these people get their lives back.
> Have you heard of someone getting "better" after taking anti-depressants and being able to come off them? No. They have to take them for life. That's not a cure.
There is no medicine in the world that you can take for a limited time to fix problems forever. That's not how medicine works. That's not how the world works.
i'm curious what is the longest conversation you've ever had with an untreated schizophrenic person?
it's so obviously a "real disease" even if we don't fully understand the biological basis. it's subjective but honestly, there are just a ton of completely obvious cases.
abuses of the psychiatric system are very bad, but schizophrenia is so so clearly real.
The audacity of pedaling a drug pricetag of $22,000 to solve someone being homeless when government safetynets won't even offer a fraction of that.
It will probably be sold for $220 in other countries.
But hopefully the compounding pharmacies and anti-pharma hacking collectives will solve the pricetag problem here.
https://www.vice.com/en/article/how-to-make-your-own-medicin...
The US will do anything and everything to solve homelessness as long as it doesn't actually involve building more homes or giving homes to people.
I mean that in a fully genuine way. Just look at how much money gets set on fire cycling the same homeless people in and out of jails and emergency rooms and you can see that nobody actually cares about the amount of money being spent, but only that homes themselves aren't easier to get.
Wait till Europe gets generics, it will cost less than $5 per month. My MS medication would cost me $8k per month in the US, costs me $2 here.
I can't stand this term 'game changer', I started noticing it being used a lot during early covid and then the Ukraine war, all for things which did not turn out to be 'game changers'.
You can see its explosive rise on Google Ngrams. Looks like we're still not quite at the peak
https://books.google.com/ngrams/graph?content=game+changer&y...
Ok, we've unchanged the game in the title above.
An unfortunate requirement of modern attention/engagement economy. Readers hate this one trick, but for the media outlets, if you don't crank up hype clickbait engine to 11, you're out, or running some very niche business.
Readers hate this one trick, click to find out why!
In the early days just before and just after AGI, all of a sudden a lot of games will be changed in a short period of time.
At $22.5K/yr it'll be more money changer than game changer.
"Double down" has a similar chart, another annoying phrase.
> Cobenfy, set to launch in October, will have a list price that would cost about $22,500 a year. The influential Institute for Clinical and Economic Review this year estimated that a price in line with expected clinical benefits to patients should be in the range of $16,000 to $20,000 a year. Bristol Myers Squibb executives say most eligible patients are covered by Medicare or Medicaid and wouldn’t pay the list price.
Didn't some bro from the pharma industry get mercilessly shat upon for charging so much for a life saving drug?
You're being downvoted for using an easily google-able factoid incorrectly because you're pattern matching on "high drug prices"
What happened was Martin Shekreli purchased patents for existing life-saving drugs and raised the price for them from $1.50 to $30 to cover the cost of the purchasing the patents themselves.
This is an entirely different.
How people feel about facts is much more important than the facts themselves.
The perception of the drug price increase much more than the details, along with other asshole things he did made him an easy target for outrage.
What is the cost of mass producing this new drug? How much profit should the company be allowed to make? Where's the outrage?
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Mostly fourchan tbh, I didn't notice it that much HN.
If only we had Terry Davis back...
He really was a genius. I think its inspiring how much high quality work he created all by himself. A true hacker IMO.
Quite a low comment. Terry Davis had schizophrenia and could code circles around just about anyone.
If the FDA was truly interested in game changing it would lead. As it is, it's a sock puppet for Big Pharma.
The FDA is under regulatory capture by the pharmaceutical industry, and their approval or lack thereof is one of the most unreliable measures of the safety and efficacy of psychiatric drugs in particular. Schizophrenia diagnoses are almost entirely subjective in nature (there's no reliable biochemical or biomolecular or biophysical test for the presence or absence of the condition) - really the whole field of psychiatric care for mental health issues is about as useful as tuberculosis experts were in the 1850s, before Koch's demonstration of the infectious microbial nature of the disease.
I’m sort of surprised to see someone claiming schizophrenia is subjective. Schizophrenia has extraordinarily pronounced symptoms. It’s like claiming lupus doesn’t exist because there’s no single reliable diagnostic test for it. Schizophrenia has very specific and easily observed symptoms and is specifically affected by medications such as Zyprexa that doesn’t cause similar changes in behavior for people without schizophrenia or psychosis. However that and related medications have horrible side effects leading most patients to avoid taking it. For people who are or have family members ravaged by schizophrenia this is some of the best news you can imagine - a medication with similar beneficial effects on their loved ones but without turning them into zombies. It feels callous to an extraordinary degree to deny the existence of schizophrenia and to not recognize the benefit to a minimal side effect mediation that can give the schizophrenics life back.
I see this take on the internet a lot usually combined with some statement of how Schizophrenics are secret geniuses and were the prophets of olden times. It just doesn't square off with my own observations of schizophrenics in real life. How is the condition subjective when you see the same types of symptoms across people? I've seen it with men and women afflicted by the condition - always the persecutory delusions, belief that they are some king or prophet/chosen one, disorganized thinking, and word salads. Why is it always the same symptoms? You're telling me that's not rooted in any common condition?
> Game changer in treatment of disease we can't even define
Doesn't quite have the same ring to it, now does it?
No it’s under pressure from people who go to the press saying “the FDA won’t let me use this drug to help me/my family” who ignore “because there’s no evidence it works” as the reason.
The pharmaceutical just has to tell those people that it does work in their particular case and just ignore the studies that say it doesn’t, and the media and politicians uncritically report that as “the FDA is mean, let pharmaceutical companies sell new and expensive snake oil and re-victimise these people”, then in a few years later the same reporters and politicians berate the “ineffectual” FDA for allowing snake oil.
Regulatory capture doesn’t mean the entire of idea of FDA as a safety mechanism is bad… nor does a legitimate reason for their existence mean that capture doesn’t exist
It is good to hold federal agencies with large power to a very high standard. But that’s often not the case as any critiques get dismissed with the “well they have good intentions and can you imagine if they didn’t exist?” hand wave tactic.
Most people if they have a mental breakdown, would be much better off if they were put in a straight jacket and thrown in a mental hospital for a year. Many of these breakdowns occur in youth/young adulthood and can be transient. But these drugs that suppress the symptoms are for life, there is no way to get off them without further mental breakdown. Its a really sad trap
As someone with firsthand experience of a sibling with schizophrenia, this comment comes off incredibly callous and ignorant.
I encourage you to learn more about this disease because you’re gravely mistaken—it is not a transient condition of early adulthood nor is untreated isolation on anyone’s treatment plan. The disease often presents in early adulthood and is a lifelong affliction thereafter. Left untreated, the condition worsens. Drugs are taken for life because the condition is incurable.
Despite the risks, I am extremely grateful for Clozapine because it’s given me time back with my brother from this horrible disease. We’ve been through a gamut of medicines and treatments like Cobenfy are welcome. Like most families, we are jubilant at the prospect of finding better treatment options with fewer risks and side effects.
Other people exhibit psychotic behaviors because they're suffering from dementia. You wouldn't go with physical restraints if a chemical relieves the behavior?