5 ms·

What takes years to develop for the human trials to start? Is it about optimizing the delivery system, or finding the right targets to test on in bigger animal

What takes years to develop for the human trials to start? Is it about optimizing the delivery system, or finding the right targets to test on in bigger animals first? There are so many people closecto dying in cancer, that finding volunteers for a Phase 1 test should be easy.

coffeemug 5y ago
Acquiring endless regulatory approvals.
- droopyEyelids 5y ago
  I wonder how much of our regulation around medicine is wasteful, vs regulation that came about in response to some sort of malfeasance.
  - AlchemistCamp 5y ago
    Most of it is probably both.
    - ok_dad 5y ago
      I worked in medical devices, and that is correct. Much of the work I did in the QA dept would not have improved the product or safety, but some of it clearly did. Can't say for medicines, as they had a different set of regs from devices.
    - rackjack 5y ago
      It is both. The last time we had very free experimentation (read: disregard for human life and suffering) we got the Nazis, the Tuskegee Syphilis Study, MKUltra, etc.. So institutions swung strongly in the opposite direction (the visible ones, at least), giving us Institutional Review Boards and such. The balance is impossible to get right either way, hence the need for Right to Try and so on.
- adamredwoods 5y ago
  I don't mind that it takes a little proof to convince regulatory boards to approve medicines for Phase I trials, but these days Phase I trials are fairly quick to get (assuming you can sell the doctors and patients on it). My guess for the delay is production process and delivery mechanisms. There are delivery mechanisms where the combinatory effects lead to some serious toxicity. Plus, how long do mice live for? I'm sure they are still taking down observations and collecting data. The article submission may be to help with funding.
steve76 5y ago
From the article: "yet it doesn’t seem to be important for normal development" Gene space is huge. My cancer is cured, but now I'm dying of mange. So that's why that mouse kept licking itself. Big ask for someone else. They have trouble getting blood thinners, statins and beta blockers right. And there's no genetics there. It's stuff people ate out in the woods for hundreds of thousands of years. > There are so many people close to dying in cancer finding volunteers for a Phase 1 test should be easy I take the opposite approach. These people have few days left. It's a time to make things nice. It can get much worse quick. Cancer, which can be managed, is nowhere near as bad as it can get. Disease tends to hit all at once. It's really just dying. Cancer, strokes, heart attacks and infections all tend to gang up at once. The trial will kill these people no doubt. If you have a ticket out of the hospital, take it! Don't squander it trying to wash mud. Also the patient pays a lot for clinical trials. Hundreds of thousands of dollars.
- verve_rat 5y ago
  Wait what? Trails aren't free to participants? That alone is going to majorly bias the results. Here take this medicine, we are fairly confident it won't kill you. Here is your $100k bill. Oh? Can't afford that? No trial for you!
  - zaroth 5y ago
    Trials are absolutely free for the participants. Insurance won’t pay for non-FDA approved treatments and it’s illegal to charge for them anyway. Ancillary routine FDA approved testing that accompanies the trials may be billed to insurance in some cases? I don’t know about that. But a trial for a novel cancer treatment will be free, if not even include an honorarium of some kind to defray costs to the patient for participating.
- tharkun__ 5y ago
  You seem to be getting downvoted. Not sure why. I've had someone in the family who got cancer. It was basically how you said it would be. They lived their life to the fullest, not thinking about the untreatable cancer. Do whatever is fun and makes you happy. At some point it got bad. No more living your life. There were bad moment. There were better moments. There were worse moments. I only saw it from afar until the very end. The last bit must have been hell for the closest family. It really is just dying. Slowly. Painfully. And all society and doctors try to do is to prolong the suffering. I'm being unfair to some people. I do know the palliative care team did their best. All volunteer doctors. Power to them.
sharkweek 5y ago
I have a friend who about 15 years ago was told he was going to die from melanoma in about a year. Within that first year he was put on a trial that added another 2 or so years to his life. Then during that time another experimental treatment was created and tested on him and that gave him another couple of years. A decade and a half later here we are, he still has cancer but his family (wife and two kids) has got to keep him around a while longer. He’s been “patient one” on a number of studies, some have helped him extend his life expectancy, others have done nothing. Sometimes he has the mental and physical energy to start a trial and other times he does not. The cancer has never gone away, and there have been so many moments of false hope that I’m never really sure where he sits mentally anymore (he really doesn’t want to talk about cancer when we’re together and I don’t think anyone can blame him) but I know he’s grateful for the chance to add more time onto his life when the experimental treatments are available.
- tomComb 5y ago
  He is both fortunate and unfortunate. Must have a very difficult fifteen years.
- 01100011 5y ago
  Yeah my friend has been doing that for about half as long. It still sucks. Some of the modern, immune-based therapies don't make your hair fall out, but they still can wreck your digestive tract, thyroid, and adrenals(in my friend's case, permanently). There are surgeries as well, and getting slowly hacked up as they chase tumor after tumor isn't fun. Still though, it's a better time to have cancer than ever I suppose.
  - sharkweek 5y ago
    I’m sorry your friend is in a similar position. There was one treatment that they were going to trial my friend on that would give him another expected extension but basically make his digestive tract stop working so he’d be pooping out of a tube into a bag the rest of his life but he declined, said it just wasn’t worth it. There have been a couple times that’s been the call he’s made and I appreciate why.
wyattpeak 5y ago
The article seems to suggest that they only just found a compound which will interfere with the gene's action. So up until now, there was nothing to test. The 2014 result only showed that gene editing before birth might prevent cancers.
stenl 5y ago
Assuming you have found a drug that is safe and binds the target in the intended way (which itself can take years), you then have to manufacture it according to GMP standards. That takes at least a year and $1 million. Next, you have to run toxicity and pharmacokinetics (how the drug is absorbed and distributed in the body) in two different animal models. That takes 6-12 months and $1-2 million. Then you apply for permission to start phase I trials, and wait for the green light. One reason RNA drugs are so exciting is that their manufacture is simple and can be standardized, cutting the GMP manufacturing step to a few weeks instead of a year or more. Small-molecule drugs are ”bespoke” in that each needs its own, different, manufacturing process. In contrast, all RNA molecules are essentially chemically identical, differing only in the ordering of the nucleotides.
Gatsky 5y ago
Need to make a drug out of the small molecule inhibitor. There is a medicinal chemistry process that takes quite a while (several years at times) to get to something you can actually give to people. Then there is safety testing in animals. Then regulatory approval. Then starting the phase I trial. The trial might take a year or more. Then you need to show the drug works compared to some standard treatment, which in a phase 3 trial in breast cancer takes 3 years and many hundreds of patients at least. Longer if you want to show it prolongs overall survival. Then the drug needs to be approved. There is also the matter of funding but there is a lot of money for early stage biotechs at the moment.
oleander73 5y ago
In my (unpopular) opinion trials for people with incurable cancer are quite predatory. You are supposed to participate to help science, not yourself. But in reality many people desperately cling to anything that gives them hope.

coffeemug 5y ago

Acquiring endless regulatory approvals.

droopyEyelids 5y ago
I wonder how much of our regulation around medicine is wasteful, vs regulation that came about in response to some sort of malfeasance.
- AlchemistCamp 5y ago
  Most of it is probably both.
  - ok_dad 5y ago
    I worked in medical devices, and that is correct. Much of the work I did in the QA dept would not have improved the product or safety, but some of it clearly did. Can't say for medicines, as they had a different set of regs from devices.
  - rackjack 5y ago
    It is both. The last time we had very free experimentation (read: disregard for human life and suffering) we got the Nazis, the Tuskegee Syphilis Study, MKUltra, etc.. So institutions swung strongly in the opposite direction (the visible ones, at least), giving us Institutional Review Boards and such. The balance is impossible to get right either way, hence the need for Right to Try and so on.
adamredwoods 5y ago
I don't mind that it takes a little proof to convince regulatory boards to approve medicines for Phase I trials, but these days Phase I trials are fairly quick to get (assuming you can sell the doctors and patients on it). My guess for the delay is production process and delivery mechanisms. There are delivery mechanisms where the combinatory effects lead to some serious toxicity. Plus, how long do mice live for? I'm sure they are still taking down observations and collecting data. The article submission may be to help with funding.

steve76 5y ago

From the article: "yet it doesn’t seem to be important for normal development" Gene space is huge. My cancer is cured, but now I'm dying of mange. So that's why that mouse kept licking itself. Big ask for someone else. They have trouble getting blood thinners, statins and beta blockers right. And there's no genetics there. It's stuff people ate out in the woods for hundreds of thousands of years. > There are so many people close to dying in cancer finding volunteers for a Phase 1 test should be easy I take the opposite approach. These people have few days left. It's a time to make things nice. It can get much worse quick. Cancer, which can be managed, is nowhere near as bad as it can get. Disease tends to hit all at once. It's really just dying. Cancer, strokes, heart attacks and infections all tend to gang up at once. The trial will kill these people no doubt. If you have a ticket out of the hospital, take it! Don't squander it trying to wash mud. Also the patient pays a lot for clinical trials. Hundreds of thousands of dollars.

verve_rat 5y ago
Wait what? Trails aren't free to participants? That alone is going to majorly bias the results. Here take this medicine, we are fairly confident it won't kill you. Here is your $100k bill. Oh? Can't afford that? No trial for you!
- zaroth 5y ago
  Trials are absolutely free for the participants. Insurance won’t pay for non-FDA approved treatments and it’s illegal to charge for them anyway. Ancillary routine FDA approved testing that accompanies the trials may be billed to insurance in some cases? I don’t know about that. But a trial for a novel cancer treatment will be free, if not even include an honorarium of some kind to defray costs to the patient for participating.
tharkun__ 5y ago
You seem to be getting downvoted. Not sure why. I've had someone in the family who got cancer. It was basically how you said it would be. They lived their life to the fullest, not thinking about the untreatable cancer. Do whatever is fun and makes you happy. At some point it got bad. No more living your life. There were bad moment. There were better moments. There were worse moments. I only saw it from afar until the very end. The last bit must have been hell for the closest family. It really is just dying. Slowly. Painfully. And all society and doctors try to do is to prolong the suffering. I'm being unfair to some people. I do know the palliative care team did their best. All volunteer doctors. Power to them.

sharkweek 5y ago

I have a friend who about 15 years ago was told he was going to die from melanoma in about a year. Within that first year he was put on a trial that added another 2 or so years to his life. Then during that time another experimental treatment was created and tested on him and that gave him another couple of years. A decade and a half later here we are, he still has cancer but his family (wife and two kids) has got to keep him around a while longer. He’s been “patient one” on a number of studies, some have helped him extend his life expectancy, others have done nothing. Sometimes he has the mental and physical energy to start a trial and other times he does not. The cancer has never gone away, and there have been so many moments of false hope that I’m never really sure where he sits mentally anymore (he really doesn’t want to talk about cancer when we’re together and I don’t think anyone can blame him) but I know he’s grateful for the chance to add more time onto his life when the experimental treatments are available.

tomComb 5y ago
He is both fortunate and unfortunate. Must have a very difficult fifteen years.
01100011 5y ago
Yeah my friend has been doing that for about half as long. It still sucks. Some of the modern, immune-based therapies don't make your hair fall out, but they still can wreck your digestive tract, thyroid, and adrenals(in my friend's case, permanently). There are surgeries as well, and getting slowly hacked up as they chase tumor after tumor isn't fun. Still though, it's a better time to have cancer than ever I suppose.
- sharkweek 5y ago
  I’m sorry your friend is in a similar position. There was one treatment that they were going to trial my friend on that would give him another expected extension but basically make his digestive tract stop working so he’d be pooping out of a tube into a bag the rest of his life but he declined, said it just wasn’t worth it. There have been a couple times that’s been the call he’s made and I appreciate why.

wyattpeak 5y ago

The article seems to suggest that they only just found a compound which will interfere with the gene's action. So up until now, there was nothing to test. The 2014 result only showed that gene editing before birth might prevent cancers.

stenl 5y ago

Assuming you have found a drug that is safe and binds the target in the intended way (which itself can take years), you then have to manufacture it according to GMP standards. That takes at least a year and $1 million. Next, you have to run toxicity and pharmacokinetics (how the drug is absorbed and distributed in the body) in two different animal models. That takes 6-12 months and $1-2 million. Then you apply for permission to start phase I trials, and wait for the green light. One reason RNA drugs are so exciting is that their manufacture is simple and can be standardized, cutting the GMP manufacturing step to a few weeks instead of a year or more. Small-molecule drugs are ”bespoke” in that each needs its own, different, manufacturing process. In contrast, all RNA molecules are essentially chemically identical, differing only in the ordering of the nucleotides.

Gatsky 5y ago

Need to make a drug out of the small molecule inhibitor. There is a medicinal chemistry process that takes quite a while (several years at times) to get to something you can actually give to people. Then there is safety testing in animals. Then regulatory approval. Then starting the phase I trial. The trial might take a year or more. Then you need to show the drug works compared to some standard treatment, which in a phase 3 trial in breast cancer takes 3 years and many hundreds of patients at least. Longer if you want to show it prolongs overall survival. Then the drug needs to be approved. There is also the matter of funding but there is a lot of money for early stage biotechs at the moment.

oleander73 5y ago

In my (unpopular) opinion trials for people with incurable cancer are quite predatory. You are supposed to participate to help science, not yourself. But in reality many people desperately cling to anything that gives them hope.