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Post by mango on Sept 13, 2018 17:47:14 GMT -5
Perhaps you just fell off the boat, but if you "OD"/hypo on aspart from a trial it would be akin to manslaughter, that's the whole point, you can't get correction with aspart as quickly without putting the participant in jeopardy. Afrezza allows you to take those corrective doses to achieve and maintain TIR much quicker and more accurately in a comparative study highlighting/comparing the pharmacokinetic advantages of subject compared to aspart This is nonsense. First everyone gets hypos on trials, both Afrezza and RAA arms - look at the Phase 3 trial. Second you are taught to use correction doses with RAA - it's expected. You must know this, it's why you need to know your correction factor. If anyone wants to learn more feel free to google correction factor. Minimally your bed time shot is a correction since there is no food involved. This real life trial involved only type 1s and if supplemental dosing is as commonplace and completely normal as you say, then nothing was in the way of stopping the aspart group from taking a follow up dose since this was a real life trial and no one was monitoring them. Why would a type 1 not take a correction dose if it is common and normal practice and especially considering they had a CGM. Would they just sit there and watch their numbers go out of range and do nothing to correct it for the sake of the clinical trial or would they do what is normal and common?
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Post by agedhippie on Sept 13, 2018 18:15:42 GMT -5
This is nonsense. First everyone gets hypos on trials, both Afrezza and RAA arms - look at the Phase 3 trial. Second you are taught to use correction doses with RAA - it's expected. You must know this, it's why you need to know your correction factor. If anyone wants to learn more feel free to google correction factor. Minimally your bed time shot is a correction since there is no food involved. This real life trial involved only type 1s and if supplemental dosing is as commonplace and completely normal as you say, then nothing was in the way of stopping the aspart group from taking a follow up dose since this was a real life trial and no one was monitoring them. Why would a type 1 not take a correction dose if it is common and normal practice and especially considering they had a CGM. Would they just sit there and watch their numbers go out of range and do nothing to correct it for the sake of the clinical trial or would they do what is normal and common? I would have expected that they would correct unless they were explicitly told not to in the protocol. If what you are concerned with is the accuracy of the meal time dose then it is possible they were told not to correct so the results would be more immediately apparent. The CGM is a bit of a red herring, trust me you do not spend your day watching your CGM, you get on with your life and let the alarms do the work (since alarms are the major advantage over the Libre). Beyond that people typically treat CGMs as a way to avoid finger pricks - want to test, look at the CGM instead. When I use a CGM I use xDrip rather than the Dexcom app because it draws me a nice projection of where I am going to be over the next few hours, if I correct it adjust, if I eat it adjusts. You can dose really aggressively with that set up - I commonly get 90%+ TIR without changing what I eat. If you see references to automated dosing systems openAPS, and Looping those are typically driven by xDrip.
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Post by sayhey24 on Sept 13, 2018 18:34:07 GMT -5
Yep, all scientific evidence from an FDA approved clinical trial. What will docs say when they see 30% less hypo and superior PPG control? Will it then become a liability to prescribe insulin apart? What happens if a patient is hospitalized from insulin apart and the clinician knew of this data but ignored it? Medical negligence? This was not a particularly well-designed trial which is why it will not create any physician liability. The protocol required both injectable and Afrezza patients to take their prandial dose and monitor with a CGM, but only the Afrezza patients were allowed to adjust dosing, twice, in response to the CGM reading while injectable patients could not adjust their dose. Should it be a surprise to anybody that patients who have the ability to act multiple times on an out-of-bounds reading on their CGM get better results than those who don't? Wouldn't a better comparison be insulin aspart vs Afrezza where both groups had a chance to adjust dosing. Heck, you could even do it with insulin aspart adjusted with Afrezza puffs. The point is that when you tie the hands of the comparator arm in a trial, physicians are not going to embrace the results. And no, this was not an FDA approved trial. Medical case studies using already approved medications within the scope of their label don't need further regulatory approval. Most hospitals will have an ethics committee / IRB approval the trial, but that is not an FDA requirement. Matt - the problem with this study was not the design. The problem is the multi-hour tail of the RAA past 2hours after a meal when the prandial should be done.
What you are suggesting is exactly what the lady from the FDA review team at the ADCOM proposed to one of the participating Affinity1 doctors who did achieve remarkable A1c reduction compared to the other trial groups. In fact she accused him of cheating because he encouraged follow-up dosing of afrezza which was allowed but just not done by most while he did not have the RAA PWDs do follow-up dosing.
She suggested if he had encouraged the RAA PWDs to follow-up dose they would have gotten results as good as afrezza. The good doctor looked her square in the eye and said he if did what she was suggesting he would have KILLED his patients. His tone literally caused her to tear-up.
Lets face it - Dr. Kendall is correct afrezza is a superior insulin to mimic meal-time pancreatic function. You can not safely do with any other medication or "insulin" what you can do with afrezza. We have know that on this board for years but now Dr. Kendall is getting the word out to the rest of the world but more important to the ADA review board. At the 2 hour mark when the prandial should be done its job, when properly dosed afrezza is far superior to any RAA. Its a done deal and beating the horse anymore provides no value. Afrezza is a superior prandial insulin.
This release today had one purpose, to further lay the foundation to justify changes to the T1 standard of care. Along with the Affinity1 results Dr. Kendall should have enough to start the process. Will he need more is the question. From what he has said it sounds like he thinks he has enough and for what its worth I agree with him.
At this point the process is underway and we should see results 1Q2019.
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Post by agedhippie on Sept 13, 2018 19:07:38 GMT -5
Matt - the problem with this study was not the design. The problem is the multi-hour tail of the RAA past 2hours after a meal when the prandial should be done.
What you are suggesting is exactly what the lady from the FDA review team at the ADCOM proposed to one of the participating Affinity1 doctors who did achieve remarkable A1c reduction compared to the other trial groups. In fact she accused him of cheating because he encouraged follow-up dosing of afrezza which was allowed but just not done by most while he did not have the RAA PWDs do follow-up dosing.
She suggested if he had encouraged the RAA PWDs to follow-up dose they would have gotten results as good as afrezza. The good doctor looked her square in the eye and said he if did what she was suggesting he would have KILLED his patients. His tone literally caused her to tear-up. That long tail is useful for meals, and bad for corrections. Getting good results in STAT is dependent on a follow up dose - that is producing a 4 hour tail from the meal which is the same as RAA. Frankly is a doctor thinks that tell his patients that using a correction with RAA will kill them I would advise those patients to find a competent endo who is capable of telling them how to do corrections (even if this one does have a nice flair for melodrama). I would suggest that perhaps the lady on the ADCOM team was tearing up with frustration rather than regret. Ultimately however, arguing that using a correction will kill them is not going to do anything at all for your credibility with Type 1s, or with endos. It simply makes them wonder what else you got wrong.
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Post by mango on Sept 13, 2018 19:35:37 GMT -5
Matt - the problem with this study was not the design. The problem is the multi-hour tail of the RAA past 2hours after a meal when the prandial should be done.
What you are suggesting is exactly what the lady from the FDA review team at the ADCOM proposed to one of the participating Affinity1 doctors who did achieve remarkable A1c reduction compared to the other trial groups. In fact she accused him of cheating because he encouraged follow-up dosing of afrezza which was allowed but just not done by most while he did not have the RAA PWDs do follow-up dosing.
She suggested if he had encouraged the RAA PWDs to follow-up dose they would have gotten results as good as afrezza. The good doctor looked her square in the eye and said he if did what she was suggesting he would have KILLED his patients. His tone literally caused her to tear-up. That long tail is useful for meals, and bad for corrections. Getting good results in STAT is dependent on a follow up dose - that is producing a 4 hour tail from the meal which is the same as RAA. Frankly is a doctor thinks that tell his patients that using a correction with RAA will kill them I would advise those patients to find a competent endo who is capable of telling them how to do corrections (even if this one does have a nice flair for melodrama). I would suggest that perhaps the lady on the ADCOM team was tearing up with frustration rather than regret. Ultimately however, arguing that using a correction will kill them is not going to do anything at all for your credibility with Type 1s, or with endos. It simply makes them wonder what else you got wrong. A follow up dose is common sense here with Afrezza. Afrezza is just insulin and so behaves like insulin. It regulates post-prandial glucose significantly well and we see the TIR and less glucose excursions and less hypos here with Afrezza because it mimics physiologic insulin and there is none of that persistence like we see with the RAAs. Afrezza provides that first-phase that is lost in people with diabetes, both 1s and 2s, and we see Afrezza restore post-prandial glucose homeostasis and these people aren't even diabetic anymore, hell they regulate their glucose like a non-diabetic and we see that in the CGMs and so this is great that people have a solution for diabetes and restoring their health. RAAs have an erratic, slow absorption and we see that in the post-prandial hyperglycemia, the acute fluctuations, the late persistence, the hypos...RAAs are not even insulin taboot.
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Post by sayhey24 on Sept 13, 2018 19:39:17 GMT -5
Aged - no, the long tail is not useful. It is dangerous. Afrezza provides the option IF NEEDED to safely follow-up dose. Its often not needed. With the RAA you have no option, you are doomed to the tail.
How many RAA users are second dosing at 90 minutes? Look, its time, just get the afrezza and stop trying to argue you can do with an RAA what you can do with afrezza. You can not. Afrezza is a superior insulin for prandial use. No one wants or needs an unpredictable tail.
If you want to argue with the trial doctor and Dr. Kendall have at it but take some advice and stop beating the horse. Afrezza will replace initial use of RAAs with T1s to reduce hypos in the standard of care, its just a matter of time. Its a done deal as MNKD now has several potential funding sources to pay the bills while Dr. Kendall closes the deal.
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Post by tiberious on Sept 13, 2018 19:57:27 GMT -5
Aged - no, the long tail is not useful. It is dangerous. Afrezza provides the option IF NEEDED to safely follow-up dose. Its often not needed. With the RAA you have no option, you are doomed to the tail. How many RAA users are second dosing at 90 minutes? Look, its time, just get the afrezza and stop trying to argue you can do with an RAA what you can do with afrezza. You can not. Afrezza is a superior insulin for prandial use. No one wants or needs an unpredictable tail. If you want to argue with the trial doctor and Dr. Kendall have at it but take some advice and stop beating the horse. Afrezza will replace initial use of RAAs with T1s to reduce hypos in the standard of care, its just a matter of time. Its a done deal as MNKD now has several potential funding sources to pay the bills while Dr. Kendall closes the deal. I remember sitting in Paramus and watching the AdCom with a bunch of ex-Mannkind folks when one of the FDA "scientists" speaking was trying to disparage Afrezza trial results by using a chart and saying that it was "inferior" because it DID NOT have the same long drawn out tail as Aspart I believe. I turned to one of the MD's in the room and asked him if I heard the FDA correctly and he just shook his head in disbelief saying they don't know what the hell they are talking about. Aged seems to follow similar lines.
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Post by agedhippie on Sept 13, 2018 20:51:37 GMT -5
That long tail is useful for meals, and bad for corrections. Getting good results in STAT is dependent on a follow up dose - that is producing a 4 hour tail from the meal which is the same as RAA. Frankly is a doctor thinks that tell his patients that using a correction with RAA will kill them I would advise those patients to find a competent endo who is capable of telling them how to do corrections (even if this one does have a nice flair for melodrama). I would suggest that perhaps the lady on the ADCOM team was tearing up with frustration rather than regret. Ultimately however, arguing that using a correction will kill them is not going to do anything at all for your credibility with Type 1s, or with endos. It simply makes them wonder what else you got wrong. A follow up dose is common sense here with Afrezza. Afrezza is just insulin and so behaves like insulin. It regulates post-prandial glucose significantly well and we see the TIR and less glucose excursions and less hypos here with Afrezza because it mimics physiologic insulin and there is none of that persistence like we see with the RAAs. Afrezza provides that first-phase that is lost in people with diabetes, both 1s and 2s, and we see Afrezza restore post-prandial glucose homeostasis and these people aren't even diabetic anymore, hell they regulate their glucose like a non-diabetic and we see that in the CGMs and so this is great that people have a solution for diabetes and restoring their health. RAAs have an erratic, slow absorption and we see that in the post-prandial hyperglycemia, the acute fluctuations, the late persistence, the hypos...RAAs are not even insulin taboot. Now that is a far better argument against RAA and something diabetics can relate to. Stick to the bolded statement framed exactly like that and you will stand a far better chance of getting traction.
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Post by agedhippie on Sept 13, 2018 21:12:15 GMT -5
Aged - no, the long tail is not useful. It is dangerous. Afrezza provides the option IF NEEDED to safely follow-up dose. Its often not needed. With the RAA you have no option, you are doomed to the tail. How many RAA users are second dosing at 90 minutes? Look, its time, just get the afrezza and stop trying to argue you can do with an RAA what you can do with afrezza. You can not. Afrezza is a superior insulin for prandial use. No one wants or needs an unpredictable tail. If you want to argue with the trial doctor and Dr. Kendall have at it but take some advice and stop beating the horse. Afrezza will replace initial use of RAAs with T1s to reduce hypos in the standard of care, its just a matter of time. Its a done deal as MNKD now has several potential funding sources to pay the bills while Dr. Kendall closes the deal. On the contrary, a long tail is very useful, it stops me from having to mess around with a second dose because I have no insulin left.In need X units of insulin for Y carbs, provided I take that I know I will be more or less flat when the tail is gone. How simple do you want it? No stopping what I am doing to test and take a second dose of Afrezza. Now obviously I am painting that more black and white than it is. The bottom line is that I mostly end up where I want to be when the insulin clears, and that's without a CGM. I think you are wrong about the future. The future for Type 1 is the smart pump/APS. The people I know on those would never give them up and I can see why. I don't see this as a big issue for Afrezza though since that leaves the Type 2 market which is 80% of diabetics.
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Post by agedhippie on Sept 13, 2018 21:17:44 GMT -5
I remember sitting in Paramus and watching the AdCom with a bunch of ex-Mannkind folks when one of the FDA "scientists" speaking was trying to disparage Afrezza trial results by using a chart and saying that it was "inferior" because it DID NOT have the same long drawn out tail as Aspart I believe. I turned to one of the MD's in the room and asked him if I heard the FDA correctly and he just shook his head in disbelief saying they don't know what the hell they are talking about. Aged seems to follow similar lines. That's a fair comment. In my experience Type 1 diabetics tend to be rather opinionated because ultimately who do you trust with your life? I can absolutely see a Type 1 not wanting a long tail and having good reason for that. I can equally see someone like me saying they are fine with a long tail because it catches those pesky slow digesting carbs. I would never tell another Type 1 that they were wrong in how they approach their treatment for that reason, and in my time I have seen some things that made me cringe.
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Post by lakers on Sept 13, 2018 21:29:54 GMT -5
A short sale pitch, the rep can remember. So can docs.
MannKind Says Afrezza Shows 'Greater Improvement' in Insulin Control vs Insulin Aspart
1:12 PM 9/13/2018 - MT Newswires 01:12 PM EDT, 09/13/2018 (MT Newswires) -- MannKind (MNKD), a developer of inhaled therapeutic products, reported Thursday new clinical data for Afrezza in type 1 diabetes which showed "significant" improvement in postprandial glucose control than insulin aspart.Compared to standard of care for mealtime therapy, the per-protocol use of Afrezza demonstrated significantly increased glucose TIR by approximately two hours per day, significantly reduced time in hyperglycemia, significantly lower PPGE one to four hours post-meal, significant reductions in glucose as early as 60 minutes following dose, and less hypoglycemia.
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Post by georgia777 on Sept 13, 2018 21:44:52 GMT -5
Never posted before as only observed and love the potential of Afrezza. That being said I have been ICU nurse for 20 yrs and witnessed(no exaggeration) 100's of pt's go low after follow up dose of aspart per MD order c blood glucose ranging from 200-250. Brutal diabetics or insulin resistant ones have bad swings. Many times wake pt up to give D50 iv in the 20's after follow doses were administered 4hrs previous. Learned to never give any insulin to someone after 2100 unless familiar c their case. Would go against MD orders for safety of pt. Reason, the tails on any SQ insulin could be dangerous to fatal. Seen it and witnessed 3 tragic results. Of course these pt's had high co-morbidities but still rough on psyche. Never been able to administer afrezza as not accepted common practice yet for tx, but dearly wished had as the quick action and clearance would have made many of our nights in ICU less stressful. And I can't tell you stress that brutal diabetics can pose to a nurse. Afrezza would be a godsend to ICU pt's capable of inhalation as no near the fear of tails. Sorry for rant but recently retired from hospital and 99% of anyone had no clue of afrezza or cgm's. Tried to talk to MDs and mostly said would look into it when accepted practice.
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Post by buyitonsale on Sept 13, 2018 23:13:21 GMT -5
I don't understand how existing writers that have been successful with prescribing and keeping patients on Afrezza are still not prescribing to more... It seems that they are only driven by patient demand and are not willing to deviate from standards.
I think it will take much more effort than reps presenting the new info...
Kendall needs to be personally involved in presenting this info to groups of targeted prescribers on a monthly basis and creating some good will.
Patient demand can only be achieved with a lot of DTC spending and I am not sure the company is ready for that.
If existing writers were to prescribe to additional few patients, the scripts would double.
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Post by nylefty on Sept 13, 2018 23:54:29 GMT -5
I don't understand how existing writers that have been successful with prescribing and keeping patients on Afrezza are still not prescribing to more... It seems that they are only driven by patient demand and are not willing to deviate from standards. I think it will take much more effort than reps presenting the new info... Kendall needs to be personally involved in presenting this info to groups of targeted prescribers on a monthly basis and creating some good will. Patient demand can only be achieved with a lot of DTC spending and I am not sure the company is ready for that. If existing writers were to prescribe to additional few patients, the scripts would double. Mike keeps saying that the current commercial is responsible for increased sales in the few markets where it's running, but I think a better spot would result in far more sales. The current ad fails to make the case that Afrezza is a better drug than its competitors!
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Post by tz on Sept 14, 2018 0:26:32 GMT -5
Insurance is the king. Mike needs strong support to convince insurance companies.
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