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Post by agedhippie on Dec 5, 2019 8:16:41 GMT -5
I do not understand how Fiasp can be considered for the ultra rapid mealtime insulin category. Must be the time to first measurable effect. Niacin? Fiasp would be considered ultra rapid because, like virtual every other major company of that size, Novo Nordisk has a whole government affairs department to make sure they get what they want.
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Post by agedhippie on Dec 5, 2019 8:20:50 GMT -5
That is pure speculation. I'd certainly take a bet against that being the case. Think far more likely if they (one or the other of FDA or ADA) do come up with a naming differentiator, it would simply be based on some thresholds for the pd profile. If you're speculation is correct then it seems Lispro would immediately qualify for this "Ultra" because MNKD's own trials used for approval would show Lispro non-inferior to Afrezza. You’re referring to non-inferior A1C results, correct? This new category has nothing to do with that. It has everything to do with the information that Peppy always post, remember? You even brought it up... That is exactly the problem. The ADA is focused on outcomes and currently that is measured by A1c. The question the insurers would ask, even if there was a new class, is whether it produces a better outcome for the extra cost and currently the trial data says no. Therefore nothing changes.
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Post by mango on Dec 5, 2019 8:21:26 GMT -5
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Post by mango on Dec 5, 2019 8:32:25 GMT -5
You’re referring to non-inferior A1C results, correct? This new category has nothing to do with that. It has everything to do with the information that Peppy always post, remember? You even brought it up... That is exactly the problem. The ADA is focused on outcomes and currently that is measured by A1c. The question the insurers would ask, even if there was a new class, is whether it produces a better outcome for the extra cost and currently the trial data says no. Therefore nothing changes. Who regulates the creation of insulin categories? ADA or FDA? Just trying to understand why you keep mentioning ADA and A1C since this new category has nothing to do with them or that.
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Post by agedhippie on Dec 5, 2019 10:51:19 GMT -5
That is exactly the problem. The ADA is focused on outcomes and currently that is measured by A1c. The question the insurers would ask, even if there was a new class, is whether it produces a better outcome for the extra cost and currently the trial data says no. Therefore nothing changes. Who regulates the creation of insulin categories? ADA or FDA? Just trying to understand why you keep mentioning ADA and A1C since this new category has nothing to do with them or that. That is actually a good question. My guess is the FDA based on guidance from the ADA. What they are looking for is a class of drug rather than an attribute though. I would expect that they are much more likely to create inhaled insulin as a class than to create ultra-rapid. Entertainingly Humalog was called ultra rapid acting when it was released back in 1996. Either way, if people are right the label gets issued as ultra rapid in February and I can wait and see
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Post by mango on Dec 5, 2019 10:56:47 GMT -5
Who regulates the creation of insulin categories? ADA or FDA? Just trying to understand why you keep mentioning ADA and A1C since this new category has nothing to do with them or that. That is actually a good question. My guess is the FDA based on guidance from the ADA. What they are looking for is a class of drug rather than an attribute though. I would expect that they are much more likely to create inhaled insulin as a class than to create ultra-rapid. Entertainingly Humalog was called ultra rapid acting when it was released back in 1996. Either way, if people are right the label gets issued as ultra rapid in February and I can wait and see Doubt ADA has anything to do with it since they deal with consensus rather than science. Plus, it’s just a non-profit organization, MannKind will be the one providing the science and justification for it.
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Post by agedhippie on Dec 5, 2019 11:17:45 GMT -5
That is actually a good question. My guess is the FDA based on guidance from the ADA. What they are looking for is a class of drug rather than an attribute though. I would expect that they are much more likely to create inhaled insulin as a class than to create ultra-rapid. Entertainingly Humalog was called ultra rapid acting when it was released back in 1996. Either way, if people are right the label gets issued as ultra rapid in February and I can wait and see Doubt ADA has anything to do with it since they deal with consensus rather than science. Plus, it’s just a non-profit organization, MannKind will be the one providing the science and justification for it. I have gone down an interesting rabbit hole, but it's not what matters. The real question is whether the class on the label matters, or if the endos just say that's nice but it's no more effective than RAA is more expensive with worse insurance cover, and requires more doses. Does simply putting a new class label move the needle - I think no but time will tell.
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Post by mango on Dec 5, 2019 11:23:04 GMT -5
Doubt ADA has anything to do with it since they deal with consensus rather than science. Plus, it’s just a non-profit organization, MannKind will be the one providing the science and justification for it. I have gone down an interesting rabbit hole, but it's not what matters. The real question is whether the class on the label matters, or if the endos just say that's nice but it's no more effective than RAA is more expensive with worse insurance cover, and requires more doses. Does simply putting a new class label move the needle - I think no but time will tell. Well Aged, you were wrong about localized insulin-derived amyloidosis ever being put in the labels, and I betcha you’re going to be wrong about this too! Time will tell though ✌️
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Post by agedhippie on Dec 5, 2019 11:26:40 GMT -5
I have gone down an interesting rabbit hole, but it's not what matters. The real question is whether the class on the label matters, or if the endos just say that's nice but it's no more effective than RAA is more expensive with worse insurance cover, and requires more doses. Does simply putting a new class label move the needle - I think no but time will tell. Well Aged, you were wrong about localized insulin-derived amyloidosis ever being put in the labels, and I betcha you’re going to be wrong about this too! Time will tell though ✌️ You may well be right. I am definitely not infallible when it comes to actions of the FDA
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Post by ktim on Dec 5, 2019 13:02:24 GMT -5
I actually haven't seen any concrete information about this proposed new category. If you know of some please forward links to it. I believe it is all speculation at this point. If you are agreeing that it likely would be based on pk/pd then there needn't be trials pitting any drugs against each other since the pk/pd profiles are already known for every insulin and it would only require deciding on a threshold for what what would be considered ultra rapid. Exactly right, the PK/PD profile. It’s only logical to have Afrezza in a category separate from the others, it’s PK/PD profile is far too different and so it is incorrect to classify it as rapid-acting when it looks nothing similar to any of the rapid acting analogs (which all have similar profiles and thus can be grouped together). All the first generation RAAs do have very similar profiles. The newer ones intended to have faster profiles do, though not yet one as fast Afrezza. So question would be where to draw a line if it makes sense to draw one at all. Of course some may believe it incorrect to include any others than the ones they are vested in and promoting
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Post by mango on Dec 5, 2019 13:10:30 GMT -5
Exactly right, the PK/PD profile. It’s only logical to have Afrezza in a category separate from the others, it’s PK/PD profile is far too different and so it is incorrect to classify it as rapid-acting when it looks nothing similar to any of the rapid acting analogs (which all have similar profiles and thus can be grouped together). All the first generation RAAs do have very similar profiles. The newer ones intended to have faster profiles do, though not yet one as fast Afrezza. So question would be where to draw a line if it makes sense to draw one at all. Of course some may believe it incorrect to include any others than the ones they are vested in and promoting See, it is not just faster IN it is faster OUT also. No other insulin or insulin analog can get OUT anywhere near as fast as Afrezza does, and most likely never will (unless they’re administered by a different ROA).. So it cannot just be fast IN it must be BOTH—Fast IN and Fast OUT. 🙂 Afrezza is BOTH. Do you see how many hours the RAA hangs around in the body compared to Afrezza? It’s going to be practically impossible for an injectable insulin to match or even come close to what Afrezza does. 😁
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Post by ktim on Dec 5, 2019 14:07:12 GMT -5
mango... looking at both is important when determining dosing requirements. Quickly searching for URLi it appears that has 19% less insulin action at 4hr to end of clamp. Is that similar enough to Lispro to not be clinically meaningful. It's quicker onset I think certainly would be. But your point kinda begs the question about whether there are multiple classes of modern prandial insulins or simply a continuum that might best be classified simply as prandial. Are we to have an RAA class, a class for Afrezza and another class for ones with rapid onset but not as fast clearance? I would think that best left up to doctors to decide whether it is a useful distinction. As a scientist but not a medical clinician I have always thought a distinction important, though your above point actually speaks to me in the opposite direction. You are pointing out that there are a lot of nuanced variations that might not be best captured by a binary classification of prandials. Of course there is the clear binary classification of insulin I have an investment in and those I do not. From that standpoint it is clear which I'd prefer getting unique recognition... though doubting it would have nearly the import some would wish.
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Post by sayhey24 on Dec 5, 2019 18:05:57 GMT -5
You’re referring to non-inferior A1C results, correct? This new category has nothing to do with that. It has everything to do with the information that Peppy always post, remember? You even brought it up... That is exactly the problem. The ADA is focused on outcomes and currently that is measured by A1c. The question the insurers would ask, even if there was a new class, is whether it produces a better outcome for the extra cost and currently the trial data says no. Therefore nothing changes. Aged - The ADA is not focused on outcomes when measured by A1c when it comes to T2s. If so insulin would be Step 2 after a long walk and diet. Whats a better outcome for insurers - lower A1c or fewer hypo's? I think hypo hospital visits are damn expensive. For insurers its fewer hypo's and the trial data clearly says the winner is afrezza.
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Post by sayhey24 on Dec 5, 2019 18:22:41 GMT -5
mango ... looking at both is important when determining dosing requirements. Quickly searching for URLi it appears that has 19% less insulin action at 4hr to end of clamp. Is that similar enough to Lispro to not be clinically meaningful. It's quicker onset I think certainly would be. But your point kinda begs the question about whether there are multiple classes of modern prandial insulins or simply a continuum that might best be classified simply as prandial. Are we to have an RAA class, a class for Afrezza and another class for ones with rapid onset but not as fast clearance? I would think that best left up to doctors to decide whether it is a useful distinction. As a scientist but not a medical clinician I have always thought a distinction important, though your above point actually speaks to me in the opposite direction. You are pointing out that there are a lot of nuanced variations that might not be best captured by a binary classification of prandials. Of course there is the clear binary classification of insulin I have an investment in and those I do not. From that standpoint it is clear which I'd prefer getting unique recognition... though doubting it would have nearly the import some would wish. ktim - what Mike said during the talk was "doctors don't know" when it comes to speed. I think he is correct. While CGM usage is old hat to us its brand new to most doctors. Doctors are going to do what the standard says. If the standard says do this, thats what they do. The importance of the new class is for the Standard of Care. Once there is a new category "ultra acting" its hard to continue to ignore afrezza. Until afrezza is front and center in the SoC it will not get the 1000's of scripts per week it should be getting.
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Post by sayhey24 on Dec 5, 2019 18:38:04 GMT -5
That is actually a good question. My guess is the FDA based on guidance from the ADA. What they are looking for is a class of drug rather than an attribute though. I would expect that they are much more likely to create inhaled insulin as a class than to create ultra-rapid. Entertainingly Humalog was called ultra rapid acting when it was released back in 1996. Either way, if people are right the label gets issued as ultra rapid in February and I can wait and see Doubt ADA has anything to do with it since they deal with consensus rather than science. Plus, it’s just a non-profit organization, MannKind will be the one providing the science and justification for it. Mango - the ADA makes the categories and develops the Standard of Care. The FDA only approves based on an agreed upon protocol. If the FDA agrees the protocol is going to measure speed of action as the basis of the study results then its speed of action as defined in the protocol. The problem is getting agreement on the protocol to determine non-inferiority. Speed of action would be something new for the FDA and was not possible in a large scale study prior to CGM technology. The label can say anything as long as the FDA approves. Today is says afrezza is a rapid acting insulin. I think Al tried for ultra rapid but that term was not know by the community so the FDA said no. MNKD was advised to work out the new category with the ADA. Once the ADA says we have a new "ultra acting" class then things will get interesting. If the ADA defines the new class as based on the time from dosing to sugars lowering, that would be a game changer for MC, afrezza and all MNKD longs.
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