[HN Gopher] FDA approves a novel drug for schizophrenia
       ___________________________________________________________________
        
       FDA approves a novel drug for schizophrenia
        
       Author : tintinnabula
       Score  : 89 points
       Date   : 2024-09-29 18:02 UTC (4 hours ago)
        
 (HTM) web link (www.washingtonpost.com)
 (TXT) w3m dump (www.washingtonpost.com)
        
       | RobotToaster wrote:
       | It's this
       | https://en.wikipedia.org/wiki/Xanomeline/trospium_chloride
        
         | kstrauser wrote:
         | > 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?
        
         | therein wrote:
         | Co-administration of an agonist and an antagonist for the same
         | pharmacophore seems like an interesting approach.
        
           | nwienert wrote:
           | 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.
        
             | swores wrote:
             | Would the opposite (work in the brain but not the body)
             | also be a healthier alternative for people addicted to
             | getting high on opiates?
        
               | johnisgood wrote:
               | 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).
        
               | nwienert wrote:
               | My want is for relieving pain in the body without making
               | me feel high, I actually assumed you want it in the body
               | not brain, as the brain effects are the feel-good
               | effects, but really not sure or familiar with how they
               | work.
        
             | Scoundreller wrote:
             | > I wanted sort of the opposite of this for opioids - work
             | in the body, not the brain
             | 
             | That's already how some anti-diarrheals work like
             | loperamide. And some anticonstipation drugs like oral
             | naloxone and methylnaltrexone that work as peripheral or
             | locally-acting antagonists
        
               | nwienert wrote:
               | Yes but loperamide doesn't alleviate pain, which maybe
               | just that opioids only alleviate pain if they do reach
               | the brain, but I did see trials for non-bbb crossing ones
               | that were for pain so not sure what's going on there.
        
       | boingo wrote:
       | https://archive.is/BYzWs
        
       | KomoD wrote:
       | > 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.
        
         | givemeethekeys wrote:
         | Didn't some bro from the pharma industry get mercilessly shat
         | upon for charging so much for a life saving drug?
        
           | the_sleaze_ wrote:
           | 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.
        
             | givemeethekeys wrote:
             | 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?
        
           | desumeku wrote:
           | Legends say that Shkreli was actually trying to rip off
           | insurance companies and left individuals alone, even going as
           | far as to give it away for $1 to people without insurance,
           | but I'm not sure.
        
       | photochemsyn wrote:
       | 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.
        
         | olliej wrote:
         | 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.
        
           | dmix wrote:
           | 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.
        
         | 77pt77 wrote:
         | > Game changer in treatment of disease we can't even define
         | 
         | Doesn't quite have the same ring to it, now does it?
        
         | fnordpiglet wrote:
         | 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.
        
         | mikhmha wrote:
         | 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?
        
       | rozab wrote:
       | 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...
        
         | drdaeman wrote:
         | 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.
        
           | olelele wrote:
           | Readers hate this one trick, click to find out why!
        
         | howard941 wrote:
         | At $22.5K/yr it'll be more money changer than game changer.
        
         | beautifulfreak wrote:
         | "Double down" has a similar chart, another annoying phrase.
        
         | unsupp0rted wrote:
         | 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.
        
         | dang wrote:
         | Ok, we've unchanged the game in the title above.
        
       | ck2 wrote:
       | 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...
        
         | johnisgood wrote:
         | 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.
        
           | devin wrote:
           | What medication?
        
         | crooked-v wrote:
         | 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.
        
           | microbug wrote:
           | imagine thinking that the "homelessness" crisis is only lack
           | of homes.
           | 
           | go talk to a sample and you'll quickly find out it ain't the
           | lack of home.
        
             | crooked-v wrote:
             | The point of my comment, in response to its parent, is that
             | people in the US are willing to support _immense_ amounts
             | of money being spent on the homeless as long as it doesn 't
             | involve housing anyone.
             | 
             | I think the institutional structure of most US states and
             | cities wouldn't blink at spend huge amounts on
             | schizophrenia drugs as long as it doesn't involve any kind
             | of inpatient treatment (forced or not) that would put a
             | roof over anyone's head.
        
           | the_optimist wrote:
           | What qualifies to you as a home? Is it "nice"? Fully
           | finished? Large? In a nice area? In an area with good
           | weather? In good repair?
        
             | crooked-v wrote:
             | In short, a couple of hundred square feet with decent
             | temperatures, a sturdy lock, and basic facilities. I
             | believe that the de facto illegalization of SROs in US
             | cities is one of the more prominent factors when it comes
             | to both invisibly and visibly homeless populations.
        
         | NHQ wrote:
         | Healthcare in the US is an elite graft, the system will pay the
         | full price. That is actually why prices are so high and
         | hospitals try to keep price tags a secret, because the bill
         | does get paid, and all those executives and investors and even
         | the insurance companies all make off with riches, increasingly
         | paid for by the public. The real crime is setting up indigent
         | people now using drugs on the street to become a massive market
         | for psychiatric medication on the pretense of a pseudo-
         | scientific "disorders" like schizophrenia.
        
       | chiefalchemist wrote:
       | If the FDA was truly interested in game changing it would lead.
       | As it is, it's a sock puppet for Big Pharma.
       | 
       | https://michaelpollan.com/books/how-to-change-your-mind/
        
       | pjmorris wrote:
       | > 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?
        
         | thefounder wrote:
         | 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.
        
           | gramie wrote:
           | > in line with recouping R&D and production costs
           | 
           | That's the "recouping R&D" part.
        
         | jdietrich wrote:
         | 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...
        
         | cma wrote:
         | 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.
        
           | givemeethekeys wrote:
           | How much of the record label's music production is funded by
           | tax dollars?
        
             | throwup238 wrote:
             | David Bowie, Mick Jagger and Keith Richards, John Lennon
             | and Paul McCartney. The list of musicians who were "on the
             | dole" to support their music careers before they made it
             | big is huge. It's almost a cliche at this point. And when
             | they do make it big, their biggest concerts are usually
             | held in stadiums that were heavily subsidized by tax
             | payers.
             | 
             | Besides, Bristol Meyers Squibb acquired this drug for $14
             | billion which is bigger than the annual budget of the
             | entire NSF. For a single drug. Tax payers weren't the ones
             | on the hook for that.
        
             | cma wrote:
             | That's fine but even considering that, is 20% only on
             | successes enough to fund the rest of the portfolio that
             | fails? And will it pass the risk free rate of return you
             | can get from money markets or treasuries or whatever?
        
             | s1artibartfast wrote:
             | In what sense are you proposing pharma production is funded
             | by tax dollars?
             | 
             | Selling a product to the taxpayers is not the same as
             | funding.
        
               | cma wrote:
               | Fundamental research is slants towards public
               | institutions, advertising and the clinical trials are the
               | main spending the drug companies do, though they have
               | research too. Lots of acquiring university spinouts as
               | well.
        
               | pjmorris wrote:
               | 'Bristol Myers Squibb executives say most eligible
               | patients are covered by Medicare or Medicaid and wouldn't
               | pay the list price.'
        
         | throwup238 wrote:
         | 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.
        
       | tomrod wrote:
       | 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
        
       | imperio59 wrote:
       | 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.)
        
         | throw18376 wrote:
         | 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.
        
         | crooked-v wrote:
         | > 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.
        
           | catlikesshrimp wrote:
           | Antibiotics (Most of the time) Everything surgery, I would
           | include gene replacement therapy and auto transplants in its
           | viccinity.
        
         | Etheryte wrote:
         | 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.
        
         | toast0 wrote:
         | > 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.
         | 
         | Some people with acute depression can take the meds, work on
         | the underlying issues and taper off, yes.
         | 
         | People with chronic depression likely need to take the meds for
         | life.
         | 
         | People with type I diabetes can't get insulin one time either.
         | People with allergies often take the allergy meds when exposed
         | to allergens, which is always for some.
         | 
         | That's not big pharma being greedy, that's a chronic condition
         | requires chronic treatment.
        
         | toastau wrote:
         | We don't have cures for diabetes, HIV/AIDS, allergies, plenty
         | of ailments. Having treatments is totally valid even if they
         | are taken forever.
         | 
         | People with the guidance of their doctor stop taking
         | antidepressants all the time. External factors aren't static
         | and often these can change. (separately or because of the
         | treatment) You do not need to stop treatment unless you and
         | your doctor have decided it is going to be better for you.
         | 
         | Another point I'd make is that we don't have exact mechanisms
         | for action in other treatments like paracetamol. That doesn't
         | make it invalid treatment.
        
           | catlikesshrimp wrote:
           | What is your doubt about paracetamol? This drug's
           | pharmacology is rather well understood.
           | 
           | About the analgesic activity
           | https://pubmed.ncbi.nlm.nih.gov/31734950/
           | 
           | About the antipyretic activity
           | https://pubmed.ncbi.nlm.nih.gov/29738273/
        
       | throw18376 wrote:
       | 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.
        
         | throwup238 wrote:
         | _> the people who cared enough and took a huge concentrated
         | risk to do this should just get rich, if in fact it pans out._
         | 
         | They already did. Bristol Myer Squibb acquired the company
         | behind this drug for $14 billion earlier this year.
        
         | lukan wrote:
         | "frankly (again if this pans out) our homelessness crisis would
         | look very different if this drug had existed 20 years ago"
         | 
         | Are there numbers, for how many homeless people, are suffering
         | from schizophrenia?
         | 
         | I would assume only a very small number of homeless people has
         | the clinical condition, but those who have it, are just very
         | visible. Most homeless people are hidden usually and avoid
         | attention.
        
           | dgacmu wrote:
           | It's actually quite high. 10%+ in this meta-analysis, and 21%
           | with some form of psychosis.
           | 
           | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880407/
           | 
           | If I were to guess, I would say that while many people may
           | experience bouts of homelessness, the ones with schizophrenia
           | are more likely to be persistently homeless.
        
           | throw18376 wrote:
           | this is completely true, but they take up a very
           | disproportionate amount of time and energy from social
           | service providers, people who work in shelters, etc, and make
           | all spaces for homeless people much more chaotic.
           | 
           | the crisis would look very different if it was just a mix of
           | people dealing with drug addiction (but basically lucid and
           | rational) and with poverty.
        
             | lukan wrote:
             | "drug addiction (but basically lucid and rational) "
             | 
             | Serious drug addicts are seldom lucid and rational.
             | 
             | But I very much do get the point, that solving the
             | schizophrenic problem, would help a lot with everything
             | else. (I am just way more sceptical, that this drug can
             | deliver that)
        
       | throwaway0665 wrote:
       | > What are "Novel" Drugs?
       | 
       | > "Novel" drugs are new drugs never before approved or marketed
       | in the U.S.
        
       | rendx wrote:
       | The Role of Childhood Trauma in Psychosis and Schizophrenia: A
       | Systematic Review
       | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8858420/
       | 
       | "Childhood Trauma is probably the most important environmental
       | factor associated with Schizophrenia. There is evidence of
       | multiple paths between traumatic experiences and psychosis.
       | Mental disorders are systems of interacting symptoms through a
       | framework of networks. Psychotic symptoms in patients with a
       | history of child abuse are more severe, persistent, and
       | refractory to treatment. In developmental years, exposure to
       | neglect and abuse reveals severe adverse effects on the average
       | neurobiological growth, leading to vulnerable neurobiology
       | preceding disadvantageous psychiatric outcomes."
       | 
       | https://www.theguesthouseocala.com/understanding-the-connect...
       | 
       | "The guiding principles of trauma-specific care can give you the
       | space to uncover the root of your schizophrenia and trauma. Thus,
       | understanding how your early traumas have impacted you opens the
       | door to dismantling maladaptive coping mechanisms. As you deepen
       | your self-understanding, it encourages you to lean into adaptive
       | coping strategies to process your experiences and life stressors.
       | Furthermore, with support, you can find a path to recovery from
       | schizophrenia and trauma that considers you and your specific
       | experiences."
        
         | throw18376 wrote:
         | i'm getting very argumentative on the internet today (under a
         | pseudonymous account because as you might guess from my
         | incessant posting, this issue is personal for me)
         | 
         | trauma (at any time), drug use, other experiences -- all can
         | make schizophrenia more likely in those susceptible. absolutely
         | true.
         | 
         | but it is a biological disease, and healing trauma won't stop
         | its progression. as your source notes, the trauma causes
         | differences in brain development, and once that's done its
         | done.
         | 
         | i don't think coming up with a new drug, the main advantage of
         | which is it _doesn 't_ numb you the horrible way existing
         | antipychotics do, is a bad thing.
         | 
         | this is basically a drug that was only created to improve the
         | QoL of people with schizophrenia. if society just wanted to
         | numb them, we already have drugs for that and could just be
         | much more aggressive in violently coercing treatment.
         | 
         | investing in these drugs isn't "looking away", it's putting in
         | a huge investment of many billions of dollars to _help_ the
         | victims live better lives.
        
       ___________________________________________________________________
       (page generated 2024-09-29 23:00 UTC)