6 ms·

Got my PhD from a lab that works on antibody drugs, they eventually even released one to the market. I’d argue that our current system is broken. There’s no re

Got my PhD from a lab that works on antibody drugs, they eventually even released one to the market. I’d argue that our current system is broken. There’s no reliable metric of drug effectiveness in any of our pre-clinical models, and thus we end up going into clinical trials quite blind indeed. And more often than not, what drug gets into trials has more to do with ego and politics than actual scientific merit. And the folks involved in these types of activities are (IMO) the most unoriginal types I’ve ever seen. There’s a lot we can do to improve our drug development process. It really doesn’t need to cost billions to bring a drug to the market. But the odds are stacked against anyone with a contrarian hypothesis and I just figured I’d save my sweat and leave this field instead.

prox 2y ago
Is this a market that can be disrupted? It sounds if you know how to save a few billion and introduce more science based drugs, it’s ripe for an overtake.
- DrScientist 2y ago
  In the same way Uber disrupted licensed taxis - or the big internet firms disrupted ad supported media. ie totally ignoring existing regulations, pretending they don't apply to you and just hoping you can push through. In a lot of the 'problems' are the regulations ( which are double edged and tricky to get right ) - and pharma companies are just following the rules. I think governments might be less lax in letting there be a new wildwest in drug development.
  - llamaimperative 2y ago
    Pointing the finger at regulation is misleading IMO. The regulations for bringing a drug to market are essentially quite simple: prove that it’s better than what currently exists. What makes it difficult is the word “prove” It turns out it’s obscenely hard to make a drug that’s good, and even harder to prove that it’s good.
    - DrScientist 2y ago
      > prove that it’s better than what currently exists. So how do you do that ethically? How do you justify taking off something that you know works to some extent and try something completely new or worse placebo? ie don't you have to construct the trial in the context of existing treatments etc? These are the kind of challenges that makes drug development slow - in the end you don't do one trial, but a series of trials, slowly building confidence and making the case. Often that's what takes the time during the clinical phase. Of course it would be much faster to go straight to a big trial that would show how well your treatment works in conditions optimal to it - however that kind of 'move-fast break-things' approach involves potentially breaking things which happen to be people. Regulation just reflects the cautious 'first do no harm' philosophy. Now let's be honest - big pharma will simultaneous complain about regulation and the cost of development, and at the same time know it creates barriers to entry - there is always some frustration about the slowest of regulatory authorities to adopt new methods - however you wouldn't want your regulatory to be gungho.
      - datavirtue 2y ago
        [flagged]
        DrScientist 2y ago
        Purdue Pharma, fentanyl and doctors abrogating responsibility for patient safety is an example of 'go wild'. On your second point - I'd agree that a lot of animal experiments are not that informative - but lets be clear 'clinical trials' are simply experiments on people. I'm not sure I'd want to give Musk, Zuckerberg or Bezos free reign to experiment on desperate people in the medical space. Depends on whether you treat people as just grist to your money making mill - or perhaps you think the ends justify the means?
        wat10000 2y ago
        Sorry, are you having difficulty with the concept that human prisoners should have more rights than mice?
  - adventured 2y ago
    There's no hoping you can push through. The US Government has complete top-down control over the sale of prescription drugs in the US, from clinicals to approval to distribution & sale. The sole reason Uber pulled off what they did, is there's no national authority governing taxi style services for all states and cities, it's a state and local effort. So Uber counted on navigating around zillions of slow local governments long enough to get big, and it worked very well. You can't do that in prescription drugs, the feds have a big hammer and can (and will) use it anytime they like.
  - jorvi 2y ago
    Uber disrupted taxis because taxis were a sleazy experience, with dirty old cars, “broken” meters and rude drivers that tried to get you to pay extortionate prices if they knew you were in a pinch. Stop trying to venerate the taxi industry, they’re horrible.
    - DrScientist 2y ago
      I think that depends on what part of the world you live in. My experience of taxi companies in the UK is that they are generally safe, reliable and operate based on reputation. My experience of taxi's in the US is that they appear to be often operated by desperate people living on the edge of existence.
      - immibis 2y ago
        Isn't that every service in the US? It takes pride on pushing the under people to the brink of death.
- ramraj07 2y ago
  Absolutely, and if you recall, even YC tried to get in on this idea. Except they did the same mistake anyone who comes up with this disruption plan commits (including Google with Calico, or Zuck with CZI) - they recruit existing academics to do the disruption. Unfortunately this just fails miserably because they’re culturally corrupted to think of standard dogmas (like there can never be a single cure for cancer). I remember a time when other such dogmas existed (remember how it was considered impossible to de-differentiate somatic cells?). The other mistake tech bros make in biology is they think they can make any cool idea work if they are smart enough. Because this is actually true in tech. But biology is restricted by laws of nature. If a drug doesn’t work, it can’t be made to work. There’s no room for wishful thinking. Third mistake I see often is individual bias towards fields that they come from. Someone who has an RNA background will only try to use RNA to solve everything, likewise with antibodies, or imaging, etc. The current research funding system incentivizes such thinking and it becomes entrenched in anyone already in this field. There’s never a thought of “which is the exact technology and approach I should use to solve this problem independent of what I’m an expert at?” So a lot of projects are doomed from the start. As long as you’re cognizant of these three facts, I think it’s very possible to disrupt this field.
  - nradov 2y ago
    Is there any plausible biological reason to think that there could ever be a single cure for cancer?
    - ckemere 2y ago
      Perhaps immune-based therapies like CAR-T are based on the premise that there are many cancerous cells in your body all the time, but your immune system deals with them, and it’s only when it fails to do so that you end up in the pathological state. So the “single cure” is the normally-functioning immune system?
      - nradov 2y ago
        That might be part of it. And yet sometimes people with normally-functioning immune systems also get cancer. So while that might be an effective treatment for some patients it's not going to be a universal cure.
DrScientist 2y ago
I'd agree with a lot of that in terms of both many drugs being 'discovered' in clinical trials as oppose to earlier ( a lot of it it about choosing the right patients and dose ), and the differences in mindsets between researchers and those often involved in the clinical trial side. One of the things you've missed is the strong restrictions put on pharma in terms of promoting use of existing drugs beyond the existing approval ( which makes sense ), and the almost complete freedom Doctors have to do what they want - they can just decide to prescribe something off-label if they think it might help. It can take a very long time for new ideas to become new products - and a lot of that is inertia ( nobody else is doing it ).
- raxxorraxor 2y ago
  I think the restrictions on pharma, while doctors have more freedom is quite helpful. There are some problems here as well where this freedom has been abused, but overall that isn't a problem in my opinion. Clinical trials are long and expensive, the medical advisory board wants compensation as well. But even startups can theoretically fund new therapies if they and their medial advisory boards get subsidies. It is a lot of risk though because for most drugs or medical devices, the real effectiveness can only be determined later in the trial itself.
JPLeRouzic 2y ago
Many thanks for saying what I suspected when looking at the research publications and clinical trials on neurodegenerative diseases. I was starting to think I was an unproductive perpetual malcontent. For example, memantine has been tested 5 times in ALS. There even no pre-clinical studies that show any positive effect of memantine in animal models. This seems so bizarre to me.
- pfisherman 2y ago
  How good are our animal models of ALS? Are they predictive of effectiveness in humans?
  - JPLeRouzic 2y ago
    I am not an expert (I am a retired R&D telecom engineer) but here is my take: * As for cancer, there are several (many?) ALS variants. The first gene to be associated with ALS was SOD1 G93A allele in 1993. It stayed the only ALS gene known until 2006. That was a curse for research as ALS with SOD1 origin is less than 2% of total cases, and even for SOD1 there are dozens of mutations associated with ALS, some with 6 months of life expectancy, others with 20 years. * Most commercial animal models are SOD1 G93A mice [0]. The G93A mutation represents roughly only 0.4-1.4% of all ALS cases worldwide, yet it is the most used animal model! SOD1 G93A ALS models are also the less costly animal models. * I think another important thing is that ALS starts often in hands (split hand phenomena) and targets skeletal muscles. But humans' nervous system for hands is very special, only shared with other upper primates. Other mammals like mice have an interneuron between the upper and lower motor neuron for hands. We do not, there is a direct connection between upper and lower motor neurons, reflecting the importance of manipulation for humans. Therefore for me, we can't prove with mice at pre-clinical stage, that a drug is efficacious or not (many drugs have some efficacy in animal models, but none in humans). * Some publications pretend they can use individual cells, fishes, or nematodes as animal models. That's laughable, it's ignoring the importance of anatomy and physiology. We are complex animals, our hormones, our immune system, and our metabolism are important to understanding ALS. The proof of that is that ALS patients who have the best life expectancy have a BMI of 27. * Other publications pretend to make their own animal models with some chemical, like BMAA, a neurotoxin found in certain cyanobacteria. Those publications smell bad behavior for me. If you want to buy a mice model of ALS: [0] https://www.jax.org/jax-mice-and-services/preclinical-research-services/neurobiology-services/amyotrophic-lateral-sclerosis-efficacy-studies/als-mouse-model-resource https://www.jax.org/jax-mice-and-services/preclinical-resear...
pfdietz 2y ago
The current system is like Churchill's description of democracy: the worst system, except for all the others. Biology is extremely complex. There's no substitute for actually trying things out on subjects in vivo. For many diseases we don't even know the cause (Alzheimer's for example). Drug companies have all the incentive in the world to improve the system to get better odds; it's not like they want drug discovery to be such a crapshoot.
- clooless 2y ago
  We also don't understand how some drugs work, either (e.g. Tylenol).
  - pfdietz 2y ago
    A utility-maximizing drug discovery system would, I think, devote some effort to biological experimentation on healthy humans, giving them chemical probes to see how that affected their biology. As is, ethics requires we get this information accidentally, for example from that famous recreational drug chemist who gave himself Parkinson's Disease with a botched synthesis that made a highly neurotoxic chemical. And some of the information comes from drug trials. A useful drug is not the only value obtained from a drug trial -- each trial is also a test of a hypothesis about the mechanisms of a disease. One of the books of the "Colossus" trilogy (about a computer that takes over the world) had the computer doing this sort of medical experimentation on randomly selected drafted subjects, with the idea of maximizing overall utility. It shows the problem with utility maximization as a goal, similar to the requirement that people give up a healthy kidney if someone else needs a transplant.
  - cess11 2y ago
    I'd say we have a rather good idea about the mechanisms for pain relief from paracetamol. Even Wikipedia has a decent summary: https://en.wikipedia.org/wiki/Paracetamol#Pharmacodynamics https://en.wikipedia.org/wiki/Paracetamol#Pharmacodynamics
- ramraj07 2y ago
  It’s ironic that you brought Alzheimer’s as an example since it exactly proves your point - drug companies pushed a therapy that targets a highly questionable _symptom_ of the disease, even though every single step of the process gave negative or inconclusive results. It was all about ego and desperate attempts to make profits using iffy drug candidates. And “biology is complex” is the type of truism I hinted at. You can always say that whenever you fail. Biology is complex and Alzheimer’s is the most complex of them all, to be sure, but I hope you’re aware of the. Alzheimer’s cabal allegations that the entire field was mutilated by a bunch of people into believing and pursuing the wrong hypotheses for decades.
mft_ 2y ago
It doesn’t (have to) cost billions to bring a (successful) drug to market. And if you pick a single successful example that was discovered in academia, was spun out into a small focussed biotech, and was in a disease area that didn’t require large or multiple studies to make it to market, you’ll have your anecdote to prove your point. Except… you’d be ignoring the costs of the 90% of drugs that fail in phase 1. You’d be ignoring the huge amount spent on discovery across the industry that never leads to a successful candidate. Drug discovery and development is difficult because, for all of our clever science, it’s still essentially serendipitous and random. And we’ve not yet figured out how to make a production line out of something that’s random, try as we might. And it’s expensive because of the failures as well as the cost associated with success.
- fragmede 2y ago
  Right. You can't just choose to run the successful clinical trials anymore than you can choose to only buy stocks that will go up on wall street. you have to run various clinical trials for a drug, and they fail. a lot. that very very expensive with no payoff. the successes have to be so phenomenally profitable that they cover the costs of all the failures. So real change would come from making the costs of those failures go away, without being able to cheat the system. The amount of medicine is believed to work, but is unpatentable, and thus doesn't have the profit motive to be pushed through clinical trials is a huge black badge on the American version of capitalism as being the best way we can organize society for the advancement of science and technology.
- edmundsauto 2y ago
  All of these things also apply to startups. And creates a VC groupthink of "portfolio theory" that necessitates huge (10,000x) returns, which costs the public a lot of viable small/medium enterprises that are not victims of the perverse incentives. I wonder if the "optimal" theory is portfolio in this case, or if there is a new generation of VC/pharma investors who want a higher probability at a lower return.
- JPLeRouzic 2y ago
  > It doesn’t (have to) cost billions to bring a (successful) drug to market > you’d be ignoring the costs of the 90% of drugs that fail in phase 1 It depends on what you call "bringing a drug to market". _________________ * Phase I costs little, around $1M during the trial, and involves only a small group of participants (one or two dozen people), so it's not multi-center and it is manageable by a few people at a biotech. The problem is that most phase I trials fail, but this is not an issue of cost, it's an issue of the way it is decided as explained by ramraj07, another commenter. Too often it is started on a hunch without solid pre-clinical data, sometimes it is because the drug was tested and failed in another disease and the managers "pivoted" to a new disease because then it costs little to try again, sometimes it's just a "weird IP/financial trick" where you combine an existing drug and an unrelated drug. Then you know you have a relatively efficacious drug, no need for toxicity studies and you can patent it. On the contrary, many trials could be done on drugs with good pre-clinical data, but that does not happen because it would be hard to patent. _________________ * A phase III costs around $25M for one or two hundred participants during the trial [0]. It lasts 6 months at most. Some publications cite much higher numbers (~$1G), but this does not make sense as drugs are often developed by biotechs (startups, in other words) with only a few million in their pockets. Another cost inflationary cause is subcontracting to CROs, as most biotechs do not have the manpower, knowledge and business connections to conduct the trial. _________________ * Once a drug receives commercialization authorization, a major company usually buys the rights and then starts the marketing phase. This starts with teaching doctors on how to prescribe and administer the drug. It means publishing articles in the mainstream medical press, inviting doctors to conferences and workshops, and paying medical sales representatives. It is costly, this is probably where are spend the ~$500M but for me, this is not drug development costs, it's just marketing costs. [0] http://idei.fr/sites/default/files/medias/doc/conf/pha/conf_2008/adams.pdf http://idei.fr/sites/default/files/medias/doc/conf/pha/conf_...
evantbyrne 2y ago
Some drugs not being able to make it into phase 1 clinical trials sounds like a functioning regulatory system to me. The bar isn't astronomically high for a phase 1. Like sure, you can't just do it in your garage like a web startup, but there are reasons for that. If anything, there are way too many drugs floating around in LDT right now, hence why those are being faded out.
Joaomcabrita 2y ago
There are companies trying to address this right? Have you seen biorce and other new ventures? Hopefully it can bring some innovation and reform to old processes. That being said, we're talking about human lives either way so it needs to be thought through and avoid unintended disasters through lack of care.

prox 2y ago

Is this a market that can be disrupted? It sounds if you know how to save a few billion and introduce more science based drugs, it’s ripe for an overtake.

DrScientist 2y ago
In the same way Uber disrupted licensed taxis - or the big internet firms disrupted ad supported media. ie totally ignoring existing regulations, pretending they don't apply to you and just hoping you can push through. In a lot of the 'problems' are the regulations ( which are double edged and tricky to get right ) - and pharma companies are just following the rules. I think governments might be less lax in letting there be a new wildwest in drug development.
- llamaimperative 2y ago
  Pointing the finger at regulation is misleading IMO. The regulations for bringing a drug to market are essentially quite simple: prove that it’s better than what currently exists. What makes it difficult is the word “prove” It turns out it’s obscenely hard to make a drug that’s good, and even harder to prove that it’s good.
  - DrScientist 2y ago
    > prove that it’s better than what currently exists. So how do you do that ethically? How do you justify taking off something that you know works to some extent and try something completely new or worse placebo? ie don't you have to construct the trial in the context of existing treatments etc? These are the kind of challenges that makes drug development slow - in the end you don't do one trial, but a series of trials, slowly building confidence and making the case. Often that's what takes the time during the clinical phase. Of course it would be much faster to go straight to a big trial that would show how well your treatment works in conditions optimal to it - however that kind of 'move-fast break-things' approach involves potentially breaking things which happen to be people. Regulation just reflects the cautious 'first do no harm' philosophy. Now let's be honest - big pharma will simultaneous complain about regulation and the cost of development, and at the same time know it creates barriers to entry - there is always some frustration about the slowest of regulatory authorities to adopt new methods - however you wouldn't want your regulatory to be gungho.
    - datavirtue 2y ago
      [flagged]
      - DrScientist 2y ago
        Purdue Pharma, fentanyl and doctors abrogating responsibility for patient safety is an example of 'go wild'. On your second point - I'd agree that a lot of animal experiments are not that informative - but lets be clear 'clinical trials' are simply experiments on people. I'm not sure I'd want to give Musk, Zuckerberg or Bezos free reign to experiment on desperate people in the medical space. Depends on whether you treat people as just grist to your money making mill - or perhaps you think the ends justify the means?
      - wat10000 2y ago
        Sorry, are you having difficulty with the concept that human prisoners should have more rights than mice?
- adventured 2y ago
  There's no hoping you can push through. The US Government has complete top-down control over the sale of prescription drugs in the US, from clinicals to approval to distribution & sale. The sole reason Uber pulled off what they did, is there's no national authority governing taxi style services for all states and cities, it's a state and local effort. So Uber counted on navigating around zillions of slow local governments long enough to get big, and it worked very well. You can't do that in prescription drugs, the feds have a big hammer and can (and will) use it anytime they like.
- jorvi 2y ago
  Uber disrupted taxis because taxis were a sleazy experience, with dirty old cars, “broken” meters and rude drivers that tried to get you to pay extortionate prices if they knew you were in a pinch. Stop trying to venerate the taxi industry, they’re horrible.
  - DrScientist 2y ago
    I think that depends on what part of the world you live in. My experience of taxi companies in the UK is that they are generally safe, reliable and operate based on reputation. My experience of taxi's in the US is that they appear to be often operated by desperate people living on the edge of existence.
    - immibis 2y ago
      Isn't that every service in the US? It takes pride on pushing the under people to the brink of death.
ramraj07 2y ago
Absolutely, and if you recall, even YC tried to get in on this idea. Except they did the same mistake anyone who comes up with this disruption plan commits (including Google with Calico, or Zuck with CZI) - they recruit existing academics to do the disruption. Unfortunately this just fails miserably because they’re culturally corrupted to think of standard dogmas (like there can never be a single cure for cancer). I remember a time when other such dogmas existed (remember how it was considered impossible to de-differentiate somatic cells?). The other mistake tech bros make in biology is they think they can make any cool idea work if they are smart enough. Because this is actually true in tech. But biology is restricted by laws of nature. If a drug doesn’t work, it can’t be made to work. There’s no room for wishful thinking. Third mistake I see often is individual bias towards fields that they come from. Someone who has an RNA background will only try to use RNA to solve everything, likewise with antibodies, or imaging, etc. The current research funding system incentivizes such thinking and it becomes entrenched in anyone already in this field. There’s never a thought of “which is the exact technology and approach I should use to solve this problem independent of what I’m an expert at?” So a lot of projects are doomed from the start. As long as you’re cognizant of these three facts, I think it’s very possible to disrupt this field.
- nradov 2y ago
  Is there any plausible biological reason to think that there could ever be a single cure for cancer?
  - ckemere 2y ago
    Perhaps immune-based therapies like CAR-T are based on the premise that there are many cancerous cells in your body all the time, but your immune system deals with them, and it’s only when it fails to do so that you end up in the pathological state. So the “single cure” is the normally-functioning immune system?
    - nradov 2y ago
      That might be part of it. And yet sometimes people with normally-functioning immune systems also get cancer. So while that might be an effective treatment for some patients it's not going to be a universal cure.

DrScientist 2y ago

I'd agree with a lot of that in terms of both many drugs being 'discovered' in clinical trials as oppose to earlier ( a lot of it it about choosing the right patients and dose ), and the differences in mindsets between researchers and those often involved in the clinical trial side. One of the things you've missed is the strong restrictions put on pharma in terms of promoting use of existing drugs beyond the existing approval ( which makes sense ), and the almost complete freedom Doctors have to do what they want - they can just decide to prescribe something off-label if they think it might help. It can take a very long time for new ideas to become new products - and a lot of that is inertia ( nobody else is doing it ).

raxxorraxor 2y ago
I think the restrictions on pharma, while doctors have more freedom is quite helpful. There are some problems here as well where this freedom has been abused, but overall that isn't a problem in my opinion. Clinical trials are long and expensive, the medical advisory board wants compensation as well. But even startups can theoretically fund new therapies if they and their medial advisory boards get subsidies. It is a lot of risk though because for most drugs or medical devices, the real effectiveness can only be determined later in the trial itself.

JPLeRouzic 2y ago

Many thanks for saying what I suspected when looking at the research publications and clinical trials on neurodegenerative diseases. I was starting to think I was an unproductive perpetual malcontent. For example, memantine has been tested 5 times in ALS. There even no pre-clinical studies that show any positive effect of memantine in animal models. This seems so bizarre to me.

pfisherman 2y ago
How good are our animal models of ALS? Are they predictive of effectiveness in humans?
- JPLeRouzic 2y ago
  I am not an expert (I am a retired R&D telecom engineer) but here is my take: * As for cancer, there are several (many?) ALS variants. The first gene to be associated with ALS was SOD1 G93A allele in 1993. It stayed the only ALS gene known until 2006. That was a curse for research as ALS with SOD1 origin is less than 2% of total cases, and even for SOD1 there are dozens of mutations associated with ALS, some with 6 months of life expectancy, others with 20 years. * Most commercial animal models are SOD1 G93A mice [0]. The G93A mutation represents roughly only 0.4-1.4% of all ALS cases worldwide, yet it is the most used animal model! SOD1 G93A ALS models are also the less costly animal models. * I think another important thing is that ALS starts often in hands (split hand phenomena) and targets skeletal muscles. But humans' nervous system for hands is very special, only shared with other upper primates. Other mammals like mice have an interneuron between the upper and lower motor neuron for hands. We do not, there is a direct connection between upper and lower motor neurons, reflecting the importance of manipulation for humans. Therefore for me, we can't prove with mice at pre-clinical stage, that a drug is efficacious or not (many drugs have some efficacy in animal models, but none in humans). * Some publications pretend they can use individual cells, fishes, or nematodes as animal models. That's laughable, it's ignoring the importance of anatomy and physiology. We are complex animals, our hormones, our immune system, and our metabolism are important to understanding ALS. The proof of that is that ALS patients who have the best life expectancy have a BMI of 27. * Other publications pretend to make their own animal models with some chemical, like BMAA, a neurotoxin found in certain cyanobacteria. Those publications smell bad behavior for me. If you want to buy a mice model of ALS: [0] https://www.jax.org/jax-mice-and-services/preclinical-research-services/neurobiology-services/amyotrophic-lateral-sclerosis-efficacy-studies/als-mouse-model-resource https://www.jax.org/jax-mice-and-services/preclinical-resear...

pfdietz 2y ago

The current system is like Churchill's description of democracy: the worst system, except for all the others. Biology is extremely complex. There's no substitute for actually trying things out on subjects in vivo. For many diseases we don't even know the cause (Alzheimer's for example). Drug companies have all the incentive in the world to improve the system to get better odds; it's not like they want drug discovery to be such a crapshoot.

clooless 2y ago
We also don't understand how some drugs work, either (e.g. Tylenol).
- pfdietz 2y ago
  A utility-maximizing drug discovery system would, I think, devote some effort to biological experimentation on healthy humans, giving them chemical probes to see how that affected their biology. As is, ethics requires we get this information accidentally, for example from that famous recreational drug chemist who gave himself Parkinson's Disease with a botched synthesis that made a highly neurotoxic chemical. And some of the information comes from drug trials. A useful drug is not the only value obtained from a drug trial -- each trial is also a test of a hypothesis about the mechanisms of a disease. One of the books of the "Colossus" trilogy (about a computer that takes over the world) had the computer doing this sort of medical experimentation on randomly selected drafted subjects, with the idea of maximizing overall utility. It shows the problem with utility maximization as a goal, similar to the requirement that people give up a healthy kidney if someone else needs a transplant.
- cess11 2y ago
  I'd say we have a rather good idea about the mechanisms for pain relief from paracetamol. Even Wikipedia has a decent summary: https://en.wikipedia.org/wiki/Paracetamol#Pharmacodynamics https://en.wikipedia.org/wiki/Paracetamol#Pharmacodynamics
ramraj07 2y ago
It’s ironic that you brought Alzheimer’s as an example since it exactly proves your point - drug companies pushed a therapy that targets a highly questionable _symptom_ of the disease, even though every single step of the process gave negative or inconclusive results. It was all about ego and desperate attempts to make profits using iffy drug candidates. And “biology is complex” is the type of truism I hinted at. You can always say that whenever you fail. Biology is complex and Alzheimer’s is the most complex of them all, to be sure, but I hope you’re aware of the. Alzheimer’s cabal allegations that the entire field was mutilated by a bunch of people into believing and pursuing the wrong hypotheses for decades.

mft_ 2y ago

It doesn’t (have to) cost billions to bring a (successful) drug to market. And if you pick a single successful example that was discovered in academia, was spun out into a small focussed biotech, and was in a disease area that didn’t require large or multiple studies to make it to market, you’ll have your anecdote to prove your point. Except… you’d be ignoring the costs of the 90% of drugs that fail in phase 1. You’d be ignoring the huge amount spent on discovery across the industry that never leads to a successful candidate. Drug discovery and development is difficult because, for all of our clever science, it’s still essentially serendipitous and random. And we’ve not yet figured out how to make a production line out of something that’s random, try as we might. And it’s expensive because of the failures as well as the cost associated with success.

fragmede 2y ago
Right. You can't just choose to run the successful clinical trials anymore than you can choose to only buy stocks that will go up on wall street. you have to run various clinical trials for a drug, and they fail. a lot. that very very expensive with no payoff. the successes have to be so phenomenally profitable that they cover the costs of all the failures. So real change would come from making the costs of those failures go away, without being able to cheat the system. The amount of medicine is believed to work, but is unpatentable, and thus doesn't have the profit motive to be pushed through clinical trials is a huge black badge on the American version of capitalism as being the best way we can organize society for the advancement of science and technology.
edmundsauto 2y ago
All of these things also apply to startups. And creates a VC groupthink of "portfolio theory" that necessitates huge (10,000x) returns, which costs the public a lot of viable small/medium enterprises that are not victims of the perverse incentives. I wonder if the "optimal" theory is portfolio in this case, or if there is a new generation of VC/pharma investors who want a higher probability at a lower return.
JPLeRouzic 2y ago
> It doesn’t (have to) cost billions to bring a (successful) drug to market > you’d be ignoring the costs of the 90% of drugs that fail in phase 1 It depends on what you call "bringing a drug to market". _________________ * Phase I costs little, around $1M during the trial, and involves only a small group of participants (one or two dozen people), so it's not multi-center and it is manageable by a few people at a biotech. The problem is that most phase I trials fail, but this is not an issue of cost, it's an issue of the way it is decided as explained by ramraj07, another commenter. Too often it is started on a hunch without solid pre-clinical data, sometimes it is because the drug was tested and failed in another disease and the managers "pivoted" to a new disease because then it costs little to try again, sometimes it's just a "weird IP/financial trick" where you combine an existing drug and an unrelated drug. Then you know you have a relatively efficacious drug, no need for toxicity studies and you can patent it. On the contrary, many trials could be done on drugs with good pre-clinical data, but that does not happen because it would be hard to patent. _________________ * A phase III costs around $25M for one or two hundred participants during the trial [0]. It lasts 6 months at most. Some publications cite much higher numbers (~$1G), but this does not make sense as drugs are often developed by biotechs (startups, in other words) with only a few million in their pockets. Another cost inflationary cause is subcontracting to CROs, as most biotechs do not have the manpower, knowledge and business connections to conduct the trial. _________________ * Once a drug receives commercialization authorization, a major company usually buys the rights and then starts the marketing phase. This starts with teaching doctors on how to prescribe and administer the drug. It means publishing articles in the mainstream medical press, inviting doctors to conferences and workshops, and paying medical sales representatives. It is costly, this is probably where are spend the ~$500M but for me, this is not drug development costs, it's just marketing costs. [0] http://idei.fr/sites/default/files/medias/doc/conf/pha/conf_2008/adams.pdf http://idei.fr/sites/default/files/medias/doc/conf/pha/conf_...

evantbyrne 2y ago

Some drugs not being able to make it into phase 1 clinical trials sounds like a functioning regulatory system to me. The bar isn't astronomically high for a phase 1. Like sure, you can't just do it in your garage like a web startup, but there are reasons for that. If anything, there are way too many drugs floating around in LDT right now, hence why those are being faded out.

Joaomcabrita 2y ago

There are companies trying to address this right? Have you seen biorce and other new ventures? Hopefully it can bring some innovation and reform to old processes. That being said, we're talking about human lives either way so it needs to be thought through and avoid unintended disasters through lack of care.