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Post by ricguy on Feb 19, 2016 9:04:24 GMT -5
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Post by agedhippie on Feb 19, 2016 12:46:52 GMT -5
The article has some basic errors but it illustrates why getting Afrezza launched was difficult. These drugs show up clean in anything but the very largest long term trials, something that Afrezza has not yet gone through. My endo, in common with all the big NYC diabetes centers, refused to prescribe Afrezza precisely because they thought there were complications out there which would only show in a larger population. Their view is that with diabetes there is little risk in waiting a couple of years to see if any issues arose. At that point they would be in a better position to offer informed advice. I expected there would be a cancer risk (if you have a lesion do you want to coat it in a growth hormone before the immune system is trying to clear it up?) but their concern was principally pulmonary fibrosis. |
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Post by pengiep on Feb 19, 2016 14:25:08 GMT -5
"If you have a lesion do you want to coat it in growth hormone". The residence time of Afrezza's monomeric insulin in the lungs is very very short, and the effective concentration at any particular part of the lung is really pretty low. It's quite a stretch to attribute any pro-oncogenic effects to Afrezza.
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Post by dictatorsaurus on Feb 19, 2016 14:30:37 GMT -5
Is that even how cancer develops or spreads? Your reasoning seems very generic and non-scientific based purely on assumption. |
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Post by agedhippie on Feb 19, 2016 16:15:56 GMT -5
Is that even how cancer develops or spreads? Your reasoning seems very generic and non-scientific based purely on assumption. It will not cause a cancer, and it will not help it spread. What it may do is help it grow. Given a pre-cancerous lesion what you are doing is introducing a growth factor into an existing situation where you really do not want things to grow and become established. Think of it like watering a plant - if it's just barren soil no amount of watering will make a plant suddenly appear, but if there is a plant there watering it will keep it alive and now you are adding Babybio in the form of insulin to help it grow. One of the reasons I avoided Januvia is because the mechanism it uses to reduce your blood sugar inhibits the mechanism the body uses to clean up pre-cancers. |
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Post by agedhippie on Feb 19, 2016 16:24:54 GMT -5
"If you have a lesion do you want to coat it in growth hormone". The residence time of Afrezza's monomeric insulin in the lungs is very very short, and the effective concentration at any particular part of the lung is really pretty low. It's quite a stretch to attribute any pro-oncogenic effects to Afrezza. That is exactly why you need larger sample sizes. If something like pancreatic cancer has a 1:25,000 occurrence rate and your Phase III trial was 1,000 people the treatment could increase the occurrence rate my an order of magnitude to 1:2,500 and the probability is that you still would not see a case. But once you start to use it in a population of a couple of hundred thousand over 70 extra cancer cases suddenly pop up and you have a problem. Hence the endo's wait and see approach. |
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Post by bill on Feb 19, 2016 17:28:51 GMT -5
"If you have a lesion do you want to coat it in growth hormone". The residence time of Afrezza's monomeric insulin in the lungs is very very short, and the effective concentration at any particular part of the lung is really pretty low. It's quite a stretch to attribute any pro-oncogenic effects to Afrezza. That is exactly why you need larger sample sizes. If something like pancreatic cancer has a 1:25,000 occurrence rate and your Phase III trial was 1,000 people the treatment could increase the occurrence rate my an order of magnitude to 1:2,500 and the probability is that you still would not see a case. But once you start to use it in a population of a couple of hundred thousand over 70 extra cancer cases suddenly pop up and you have a problem. Hence the endo's wait and see approach. Baloney. What you said would be true if Afrezza provided no benefits over injected insulin. However, that's not the case. Therefore, one SHOULD be weighing the tangible benefits of using Afrezza; better glucose control and a lesser chance of hypos against a potential cancer risk which may or may not even be relevant. Not that hard a choice to make given Afrezza's track record to date. I believe it's the height of ignorance for an endo to shy away from a superior treatment in many ways because of a potential low probability risk which may or may not ever be meaningful. |
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Post by thoth on Feb 19, 2016 17:39:58 GMT -5
The article has some basic errors but it illustrates why getting Afrezza launched was difficult. These drugs show up clean in anything but the very largest long term trials, something that Afrezza has not yet gone through. My endo, in common with all the big NYC diabetes centers, refused to prescribe Afrezza precisely because they thought there were complications out there which would only show in a larger population. Their view is that with diabetes there is little risk in waiting a couple of years to see if any issues arose. At that point they would be in a better position to offer informed advice. I expected there would be a cancer risk (if you have a lesion do you want to coat it in a growth hormone before the immune system is trying to clear it up?) but their concern was principally pulmonary fibrosis. I'm curious: have these same endos also stopped prescribing all of these popular diabetes drugs because now there's potential data which shows complications? If not, their logic is flawed. They are willingly subjecting patients to a real risk vs. the mere possibility that Afrezza may cause a problem down the line when there's no existing evidence for the latter. The cancer risk also cuts both ways. There is an increasing body of research linking insulin resistance and obesity to cancer. Afrezza's ability to reduce those overall risk factors in diabetics needs to be weighted against any possible risk to the lungs. |
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Post by agedhippie on Feb 19, 2016 21:46:09 GMT -5
That is exactly why you need larger sample sizes. If something like pancreatic cancer has a 1:25,000 occurrence rate and your Phase III trial was 1,000 people the treatment could increase the occurrence rate my an order of magnitude to 1:2,500 and the probability is that you still would not see a case. But once you start to use it in a population of a couple of hundred thousand over 70 extra cancer cases suddenly pop up and you have a problem. Hence the endo's wait and see approach. Baloney. What you said would be true if Afrezza provided no benefits over injected insulin. However, that's not the case. Therefore, one SHOULD be weighing the tangible benefits of using Afrezza; better glucose control and a lesser chance of hypos against a potential cancer risk which may or may not even be relevant. Not that hard a choice to make given Afrezza's track record to date. I believe it's the height of ignorance for an endo to shy away from a superior treatment in many ways because of a potential low probability risk which may or may not ever be meaningful. The point is that the trials data does not support that statement and trials data is what the medical world works off. At best the trial data says Afrezza is non-inferior and that makes them equivalent. In risk management if you have two equivalent options and one option may have an unquantifiable risk you avoid that option until the risk can be quantified. This is what is happening. Until there is new data or sufficient time has elapsed to allow the risk to be quantified they will wait because the current trial data says there is nothing to be gained. |
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Post by agedhippie on Feb 19, 2016 21:58:18 GMT -5
The article has some basic errors but it illustrates why getting Afrezza launched was difficult. These drugs show up clean in anything but the very largest long term trials, something that Afrezza has not yet gone through. My endo, in common with all the big NYC diabetes centers, refused to prescribe Afrezza precisely because they thought there were complications out there which would only show in a larger population. Their view is that with diabetes there is little risk in waiting a couple of years to see if any issues arose. At that point they would be in a better position to offer informed advice. I expected there would be a cancer risk (if you have a lesion do you want to coat it in a growth hormone before the immune system is trying to clear it up?) but their concern was principally pulmonary fibrosis. I'm curious: have these same endos also stopped prescribing all of these popular diabetes drugs because now there's potential data which shows complications? If not, their logic is flawed. They are willingly subjecting patients to a real risk vs. the mere possibility that Afrezza may cause a problem down the line when there's no existing evidence for the latter. The cancer risk also cuts both ways. There is an increasing body of research linking insulin resistance and obesity to cancer. Afrezza's ability to reduce those overall risk factors in diabetics needs to be weighted against any possible risk to the lungs. Will they stop prescribing popular diabetes drugs? Absolutely, look at what happened to Actos and Advandia or even Lantus when they hit problems. Doctors back away until things become clearer. The problem for Afrezza is the non-inferiority rating. So you have two apparently interchangeable insulins, one with a black box warning and one without, this isn't a difficult choice. For this dynamic to change there has to be trial data showing superiority. |
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Post by agedhippie on Feb 19, 2016 22:01:20 GMT -5
To be clear: In the two above cases I thought there was a cancer risk, my endo did not. Rather they thought there was a pulmonary fibrosis risk, that is what was concerning them.
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Post by benyiju on Feb 19, 2016 22:01:30 GMT -5
Baloney. What you said would be true if Afrezza provided no benefits over injected insulin. However, that's not the case. Therefore, one SHOULD be weighing the tangible benefits of using Afrezza; better glucose control and a lesser chance of hypos against a potential cancer risk which may or may not even be relevant. Not that hard a choice to make given Afrezza's track record to date. I believe it's the height of ignorance for an endo to shy away from a superior treatment in many ways because of a potential low probability risk which may or may not ever be meaningful. The point is that the trials data does not support that statement and trials data is what the medical world works off. At best the trial data says Afrezza is non-inferior and that makes them equivalent. In risk management if you have two equivalent options and one option may have an unquantifiable risk you avoid that option until the risk can be quantified. This is what is happening. Until there is new data or sufficient time has elapsed to allow the risk to be quantified they will wait because the current trial data says there is nothing to be gained. Hippie, you're arguing with the Old Believers, it's pointless. They only want to hear things that confirm their MNKD investment theory (which for most of them is some sort of get-rich-quick fantasy). What you're saying is absolutely correct, so I'm glad you're saying it, but don't waste your time responding to these kinds of posts. |
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Post by tayl5 on Feb 19, 2016 23:54:25 GMT -5
There is a high degree of variation in how much insulin a patient needs to control his or her glucose level. While the net effect on glucose control is the same, the amount of circulating insulin is much higher in those patients that need a high dose. Except in very small tumors, the high doses of insulin would circulate through the tumor in the blood vessels that feed it, but as far as I know there's no evidence of accelerated dose-dependent cancer growth. On the other hand, cancers run on glucose and high blood sugar levels must be like a tumor all-you-can-eat buffet. The "cautious" endos have their science on backwards.
One of the things that always makes me wonder is why a drug company needs to show statistical significance of efficacy for approval but a few random occurences of an adverse effect that are not statistically significant trigger a warning on the label.
There's something to be said for not being an early adopter of new drugs but at some point the benefits clearly outweigh the risk and the doctor is doing his or her patients a real disservice by avoiding the drug.
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Post by liane on Feb 20, 2016 6:30:59 GMT -5
benyiju, Your posts are getting quite tiresome. It's perfectly OK to state your point of view - positive, negative, or whatever. But you really need to quit labeling the other posters on this board. Word to the wise...
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Post by agedhippie on Feb 20, 2016 11:15:50 GMT -5
There is a high degree of variation in how much insulin a patient needs to control his or her glucose level. While the net effect on glucose control is the same, the amount of circulating insulin is much higher in those patients that need a high dose. Except in very small tumors, the high doses of insulin would circulate through the tumor in the blood vessels that feed it, but as far as I know there's no evidence of accelerated dose-dependent cancer growth. On the other hand, cancers run on glucose and high blood sugar levels must be like a tumor all-you-can-eat buffet. The "cautious" endos have their science on backwards. One of the things that always makes me wonder is why a drug company needs to show statistical significance of efficacy for approval but a few random occurences of an adverse effect that are not statistically significant trigger a warning on the label. There's something to be said for not being an early adopter of new drugs but at some point the benefits clearly outweigh the risk and the doctor is doing his or her patients a real disservice by avoiding the drug. That cancer is insulin dose dependent is the whole basis of the theory that in Type 2 elevated insulin levels are a risk factor in cancer. There are a lot of papers on this. It surprised me when I first came across it as well. This is not to say that insulin causes cancer but rather that if a cancer exists high insulin levels may assist (and that it is a theory). Endos are well aware of the Warburg effect since it is squarely in their wheelhouse, but in this case it is not relevant. Saying cancers run on glucose is correct but also somewhat misleading. What makes the Warburg effect important is not that cancer cells use glucose for growth, all cells do that, but rather the way it uses glucose. All cells use both an oxidative phosphorylation and aerobic glycolysis process to produce energy (ATP). Of these two methods glycolysis is far less efficient so in the presence of oxygen cells do not use glycolysis. The exception is cancer cells which only use glycolysis. Exactly why they behave like this is unknown although there are a lot of theories. I agree that at some point the benefits outweigh the risk however that point is a year or two after mass adoption or a superiority study. Until then the choice is two insulins, one with a black box warning. |
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