5 ms·

Quietly another drug candidate disappears

73 points by dcminter 7y ago

pmiller2 7y ago
Isn’t this the normal, expected, and preferred method for a drug to fail? The alternative failure mode is: drug gets to market, later on is found to have horrible side effects and harms a lot of people. See e.g. Vioxx.
- dvh 7y ago
  I think the reverse is also more common. Drug get pass the "causes no harm" phase and they start putting it into everything. Recently I've seen glue used as both spermicide and in eye drops.
  - dvh 7y ago
    I really don't understand why am I being downvoted. The drug in question is Carbomer 974P which is bioadhesive (a glue) and is used in spermicides and eydrops (e.g. Oftagel). Similar drug that is recently being put into everything is hyaluronic acid.
- dcminter 7y ago
  Oh, absolutely - but I think Derek's point in the article is that many critics of "Big Bad Pharma" who see the profitable drugs making it to market are unaware of the expensive failures that never make it that far.
  - skohan 7y ago
    > many critics of "Big Bad Pharma" who see the profitable drugs making it to market are unaware of the expensive failures that never make it that far. But I think this image - that pharmaceutical companies are constantly risking their financial future pouring resources into research for new drugs which will finally cure some disease that has plagued humanity - is also a mischaracterization of reality. For instance, drug companies also spend a large portion of their research budget developing "novel compounds" which are based on small chemical changes to existing drugs, just for the purpose of extending their patent and increasing the profitability (read: cost to consumer) of an existing treatment. So it's not as if all the resources they put in to research represent some altruistic good. To be honest, I think the incentive structure for drug companies, like many things in healthcare, is just not ideal for producing the best outcomes. Their ideal business model is to own expensive drugs which sick people have to take for their entire lives. If they produce truly curative treatments, that's actually a net loss for them. As some people have suggested, it would make a lot of sense to nationalize drug research in the US. The idea is you bring the top pharmaceutical researchers into the NIH, and while this would require a big up-front investment, you might even be able to operate at a profit by licensing the drugs they develop to the rest of the world. Also, in a single-payer world, you would have the healthcare provider under the same financial umbrella as the people creating the drugs. As a result, the incentive would be to drive treatment costs down.
    - new299 7y ago
      > just for the purpose of extending their patent I don’t understand this point, though I’ve heard it before. If the original patents expire, the original drugs can be manufactured as generics right? If the new patents provide no new benefit, don’t use them? > The idea is you bring the top pharmaceutical researchers into the NIH... Projects I’ve seen suggests that technology development carried out in an academic context often requires significant refinement (or complete reworking tbh) when being brought to market. So, it’s not clear to me how well the model you suggest would work. Perhaps it would be best to have a public organization that manufactures genetic drugs first and build from that. But... I think that may also have issues.
      - skohan 7y ago
        > I don’t understand this point, though I’ve heard it before. If the original patents expire, the original drugs can be manufactured as generics right? If the new patents provide no new benefit, don’t use them? So it's because of a loophole created in the Hatch-Waxman act, which basically stipulates that if a drug company creates a "new chemical version" of a name-brand drug, then it's possible to extend the patent for 5 years and block the FDA approval of any generics. [0] [0]: https://www.upcounsel.com/how-long-does-a-drug-patent-last https://www.upcounsel.com/how-long-does-a-drug-patent-last > Projects I’ve seen suggests that technology development carried out in an academic context often requires significant refinement (or complete reworking tbh) when being brought to market. So, it’s not clear to me how well the model you suggest would work. So the problem, as I see it, is that the people who profit from the production and sale of drugs also have an essential monopoly over the talent pool which is capable of developing new drugs. As a result, the incentive is for them to direct their R&D resources in ways which maximize profitability rather than maximize health outcomes. In such a system as I have described, there would still be room for drug companies to do the work of producing drugs, but the incentives for the R&D process could be aligned with the general population rather than drug company shareholders. The current system represents something of a conflict of interest.
        refurb 7y ago
- C1sc0cat 7y ago
  Or Thalidomide which luckily for the USA was stopped by the FDA.
  - ncmncm 7y ago
    An example of sexism causing tragedy. It was only tested on male animals because they were easier, and it was allowed.
russellbeattie 7y ago
Slightly off topic, but the author of this article is Derek Lowe who I know from his series called "Things I Won't Work With" which contains some amazing facts and hysterical observations. He wrote a new entry in August that I hadn't seen (the first in a few years). Definitely check it out. https://blogs.sciencemag.org/pipeline/archives/category/things-i-wont-work-with https://blogs.sciencemag.org/pipeline/archives/category/thin...
- mirimir 7y ago
  Love "Things I Won't Work With"!
- C1sc0cat 7y ago
  Great read I love the euphemism of "energetic materials chemists"
- dcminter 7y ago
  By the by it's often worth skimming through the comment threads on those articles for entertaining posts by chemists reminiscing about their own near-misses!
Angostura 7y ago
I don't know enough about the area to be able to interpret this seemingly rather important sentence: > word has just come out that the study has been terminated with only about a third of its patients enrolled. Was the study terminated because they couldn't find sufficient guinea-pigs? Or was the study terminated for other reasons before recuitment was complete?
- SiempreViernes 7y ago
  Well, the title of the linked article is "Biogen axes phase 2 study of lung-scarring med due to 'safety concerns'"
- refurb 7y ago
  There can be a lot of reasons why a study is terminated before they hit full enrollment. They might be looking for very specific types of patients that are just really hard to find. Or, there may be plenty of patients out there, but the consensus is that the likelihood of the drug working is so low that doctors are recommending to patients they don’t enroll. I’m guessing it’s the 2nd and it’s just another nail in the coffin for this program as clinical trial delays add a ton of costs.
ImaCake 7y ago
I know some people who work with mice models of fibrosis (but in a COPD disease context). They work extremely hard and produce mammoth amounts of experimental data. They could always do with more funding and more manpower, but I feel good that at least some of the people working on these diseases are exactly who you would hope would be.
dna_polymerase 7y ago
> Drugs fail all the time, most of the time rather quietly, and all the work and money that went into them just sort of vanishes. This seems problematic to me. Wouldn't it be generally preferable to publish everything about their work so others can learn from it? Obviously big pharma would be against that, but in the general pursuit of advancing medicine it would help, so federal regulation?
- chris5745 7y ago
  I was thinking similar thoughts. I imagine a lot of efforts are duplicated in all industries. New players have to make many of the same mistakes established players made, and this is part of the barrier to entry. Someone could potentially make a killing managing a marketplace for buying and selling failed industrial results. We learn from mistakes. If it were cheaper to learn from others’ mistakes than make them anew, this could have huge benefits for everyone. But it would have to be very enticing for the established players.
- jcranmer 7y ago
  Derek is speaking here about how the effort is vanishing in the public eye. But if you're someone doing research on a drug target, these sorts of failures are going to be visible to you when you do searches for previous attempts or approaches at the problem, at least if they advance as far as initial clinical trials.
- NikolaeVarius 7y ago
  A drug failing doesn't mean a company can't do work improving it or building on top of it
ncmncm 7y ago
For conditions that are as poorly defined as fibrosis -- i.e., a symptom is noted, but not a cause -- RCTs can produce tragically misleading results, resulting in excellent therapies being dropped. Apparently most treatments for depression fall in this range, which may be why new treatments arrive so rarely. Depression is a "wastebasket" diagnosis, with many, many causes. Any given treatment only helps with one or a few. Which variety you have can only be discovered by seeing which medications fix it, so putting together a set of candidates who have what one treatment would fix is impossible without actually trying it on them first. If fibroses have this character, the only medication we can hope will get past the gauntlet will be palliative treatments, that reduce the body's common response to all the causes, without addressing any of the causes. It's as if we were treating "ague", and not differentiating flu from malaria or bacterial pneumonia. Since a candidate antibiotic may only help the few with gram-negative bacterial infection, it looks not sufficiently effective, and is dropped. We are left with aspirin for fever and decongestants, while the infection rages unchecked.

73 points by dcminter 7y ago

Isn’t this the normal, expected, and preferred method for a drug to fail? The alternative failure mode is: drug gets to market, later on is found to have horrible side effects and harms a lot of people. See e.g. Vioxx.

dvh 7y ago
I think the reverse is also more common. Drug get pass the "causes no harm" phase and they start putting it into everything. Recently I've seen glue used as both spermicide and in eye drops.
- dvh 7y ago
  I really don't understand why am I being downvoted. The drug in question is Carbomer 974P which is bioadhesive (a glue) and is used in spermicides and eydrops (e.g. Oftagel). Similar drug that is recently being put into everything is hyaluronic acid.
dcminter 7y ago
Oh, absolutely - but I think Derek's point in the article is that many critics of "Big Bad Pharma" who see the profitable drugs making it to market are unaware of the expensive failures that never make it that far.
- skohan 7y ago
  > many critics of "Big Bad Pharma" who see the profitable drugs making it to market are unaware of the expensive failures that never make it that far. But I think this image - that pharmaceutical companies are constantly risking their financial future pouring resources into research for new drugs which will finally cure some disease that has plagued humanity - is also a mischaracterization of reality. For instance, drug companies also spend a large portion of their research budget developing "novel compounds" which are based on small chemical changes to existing drugs, just for the purpose of extending their patent and increasing the profitability (read: cost to consumer) of an existing treatment. So it's not as if all the resources they put in to research represent some altruistic good. To be honest, I think the incentive structure for drug companies, like many things in healthcare, is just not ideal for producing the best outcomes. Their ideal business model is to own expensive drugs which sick people have to take for their entire lives. If they produce truly curative treatments, that's actually a net loss for them. As some people have suggested, it would make a lot of sense to nationalize drug research in the US. The idea is you bring the top pharmaceutical researchers into the NIH, and while this would require a big up-front investment, you might even be able to operate at a profit by licensing the drugs they develop to the rest of the world. Also, in a single-payer world, you would have the healthcare provider under the same financial umbrella as the people creating the drugs. As a result, the incentive would be to drive treatment costs down.
  - new299 7y ago
    > just for the purpose of extending their patent I don’t understand this point, though I’ve heard it before. If the original patents expire, the original drugs can be manufactured as generics right? If the new patents provide no new benefit, don’t use them? > The idea is you bring the top pharmaceutical researchers into the NIH... Projects I’ve seen suggests that technology development carried out in an academic context often requires significant refinement (or complete reworking tbh) when being brought to market. So, it’s not clear to me how well the model you suggest would work. Perhaps it would be best to have a public organization that manufactures genetic drugs first and build from that. But... I think that may also have issues.
    - skohan 7y ago
      > I don’t understand this point, though I’ve heard it before. If the original patents expire, the original drugs can be manufactured as generics right? If the new patents provide no new benefit, don’t use them? So it's because of a loophole created in the Hatch-Waxman act, which basically stipulates that if a drug company creates a "new chemical version" of a name-brand drug, then it's possible to extend the patent for 5 years and block the FDA approval of any generics. [0] [0]: https://www.upcounsel.com/how-long-does-a-drug-patent-last https://www.upcounsel.com/how-long-does-a-drug-patent-last > Projects I’ve seen suggests that technology development carried out in an academic context often requires significant refinement (or complete reworking tbh) when being brought to market. So, it’s not clear to me how well the model you suggest would work. So the problem, as I see it, is that the people who profit from the production and sale of drugs also have an essential monopoly over the talent pool which is capable of developing new drugs. As a result, the incentive is for them to direct their R&D resources in ways which maximize profitability rather than maximize health outcomes. In such a system as I have described, there would still be room for drug companies to do the work of producing drugs, but the incentives for the R&D process could be aligned with the general population rather than drug company shareholders. The current system represents something of a conflict of interest.
      - refurb 7y ago
C1sc0cat 7y ago
Or Thalidomide which luckily for the USA was stopped by the FDA.
- ncmncm 7y ago
  An example of sexism causing tragedy. It was only tested on male animals because they were easier, and it was allowed.

russellbeattie 7y ago

Slightly off topic, but the author of this article is Derek Lowe who I know from his series called "Things I Won't Work With" which contains some amazing facts and hysterical observations. He wrote a new entry in August that I hadn't seen (the first in a few years). Definitely check it out. https://blogs.sciencemag.org/pipeline/archives/category/things-i-wont-work-with https://blogs.sciencemag.org/pipeline/archives/category/thin...

mirimir 7y ago
Love "Things I Won't Work With"!
C1sc0cat 7y ago
Great read I love the euphemism of "energetic materials chemists"
dcminter 7y ago
By the by it's often worth skimming through the comment threads on those articles for entertaining posts by chemists reminiscing about their own near-misses!

Angostura 7y ago

I don't know enough about the area to be able to interpret this seemingly rather important sentence: > word has just come out that the study has been terminated with only about a third of its patients enrolled. Was the study terminated because they couldn't find sufficient guinea-pigs? Or was the study terminated for other reasons before recuitment was complete?

SiempreViernes 7y ago
Well, the title of the linked article is "Biogen axes phase 2 study of lung-scarring med due to 'safety concerns'"
refurb 7y ago
There can be a lot of reasons why a study is terminated before they hit full enrollment. They might be looking for very specific types of patients that are just really hard to find. Or, there may be plenty of patients out there, but the consensus is that the likelihood of the drug working is so low that doctors are recommending to patients they don’t enroll. I’m guessing it’s the 2nd and it’s just another nail in the coffin for this program as clinical trial delays add a ton of costs.

ImaCake 7y ago

I know some people who work with mice models of fibrosis (but in a COPD disease context). They work extremely hard and produce mammoth amounts of experimental data. They could always do with more funding and more manpower, but I feel good that at least some of the people working on these diseases are exactly who you would hope would be.

dna_polymerase 7y ago

> Drugs fail all the time, most of the time rather quietly, and all the work and money that went into them just sort of vanishes. This seems problematic to me. Wouldn't it be generally preferable to publish everything about their work so others can learn from it? Obviously big pharma would be against that, but in the general pursuit of advancing medicine it would help, so federal regulation?

chris5745 7y ago
I was thinking similar thoughts. I imagine a lot of efforts are duplicated in all industries. New players have to make many of the same mistakes established players made, and this is part of the barrier to entry. Someone could potentially make a killing managing a marketplace for buying and selling failed industrial results. We learn from mistakes. If it were cheaper to learn from others’ mistakes than make them anew, this could have huge benefits for everyone. But it would have to be very enticing for the established players.
jcranmer 7y ago
Derek is speaking here about how the effort is vanishing in the public eye. But if you're someone doing research on a drug target, these sorts of failures are going to be visible to you when you do searches for previous attempts or approaches at the problem, at least if they advance as far as initial clinical trials.
NikolaeVarius 7y ago
A drug failing doesn't mean a company can't do work improving it or building on top of it

ncmncm 7y ago

For conditions that are as poorly defined as fibrosis -- i.e., a symptom is noted, but not a cause -- RCTs can produce tragically misleading results, resulting in excellent therapies being dropped. Apparently most treatments for depression fall in this range, which may be why new treatments arrive so rarely. Depression is a "wastebasket" diagnosis, with many, many causes. Any given treatment only helps with one or a few. Which variety you have can only be discovered by seeing which medications fix it, so putting together a set of candidates who have what one treatment would fix is impossible without actually trying it on them first. If fibroses have this character, the only medication we can hope will get past the gauntlet will be palliative treatments, that reduce the body's common response to all the causes, without addressing any of the causes. It's as if we were treating "ague", and not differentiating flu from malaria or bacterial pneumonia. Since a candidate antibiotic may only help the few with gram-negative bacterial infection, it looks not sufficiently effective, and is dropped. We are left with aspirin for fever and decongestants, while the infection rages unchecked.