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Post by prcgorman2 on Jun 15, 2023 17:43:30 GMT -5
The problem is simply that BP no longer believes in inhaled insulin. They have seen two of their own fail (Pfizer and Sanofi), and eight years after launch Afrezza sales are a rounding error in the market. It's hard to emphasis how negligible the Afrezza market share. Take just Humalog (ignore Novolog and all the newer insulins) who had TRx 726.4k in May, Afrezza TRx was 3.8k. Afrezza undersold even Humulin R which nobody should be using at this point by 8:1. I think pediatrics has the potential to double Afrezza sales, but not much beyond that because endos are pushing AID pumps. That's my opinion, but it based on talking to several endos in the big NYC teaching hospitals (donate to hospital groups; (a) it helps the diabetes centers which are never profit generating, (b) it gets you access to people) I think it's likely correct. Mannkind owns Afrezza whether they want to or not so it's high time they did something about improving sales and that means large trials to get the data proving superior outcomes in various scenarios. Then you may see a partner emerge, but maybe you wouldn't want one at that point... The ole pesky chicken or the egg strikes again. Well, if we agree it’s MNKD who continues to bear the burden, for now, we’re the chicken. It’s fair to say eggs have been laid, and what hatched came home to roost. Need new eggs. Nice shiny epic embarassing gold ones. If MannKind is ever spectacularly successful, then instead of being the chicken, MNKD will be the goose. The one that laid the golden eggs. |
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Post by agedhippie on Jun 15, 2023 17:43:30 GMT -5
... I have a real problem with the way TIR is being evolved and is being used. The 70-180 24hr TIR which is becoming the "norm" is not giving us a true picture at addressing the hard problem. The hard problem is when people eat their blood sugar goes crazy. IMO, at a minimum TIR needs broken into two separate TIRs; awake; and sleeping. For the T2 do we really care about when they are sleeping? I would say for the most part no. If when they go to bed they are at 95 mg/dl their pancreas should carry them through the night with no issues. The key is post prandial control and returning the T2 to a non-diabetic range under 140 asap. For the T1 its a different story as their basal needs to carry them through the night and requires adjustment. For Aged's AID pump - it does a super job when the T1 is sleeping but can not match up to afrezza for post prandial control. However, when you mush the two TIR periods together and you provide the 180 upper limit, it tells a different story but its the story the AID pump vendors want to tell. Time in Range is defined as time between 70-180 over 24hr. You can argue that's not fair, but that's the agreed measure. The idea that T2 diabetics don't care about high levels when they are asleep is simply wrong. That's a third of the day with elevated levels which is not a good idea. They still have insulin resistance, they are still not producing enough insulin, their body is still churning out glucose. This approach will not even get to the starting gate. People here wanted TIR as the measure and now you have it. The catch is that diabetes treatment comprises both basal and prandial with TIR being the value for that entire treatment. Just prove that Afrezza plus basal gives better TIR than an AID pump and you are in business. If it looks like MNKD are making excuses it just destroys credibility with the endos. |
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Post by prcgorman2 on Jun 15, 2023 17:47:20 GMT -5
True, we wanted TIR. What we didn’t count on was it being set appropriate for old less effective therapies. We should have seen that coming. Fighting it would have been futile of course. But, what we can do now is kick it’s ass, and your example of a way to do that is valid. Do you suppose the upcoming(?) pump switch trial might have improved TIR as a goal?
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Post by agedhippie on Jun 15, 2023 19:28:19 GMT -5
True, we wanted TIR. What we didn’t count on was it being set appropriate for old less effective therapies. We should have seen that coming. Fighting it would have been futile of course. But, what we can do now is kick it’s ass, and your example of a way to do that is valid. Do you suppose the upcoming(?) pump switch trial might have improved TIR as a goal? There is no way anyone in the medical is going to take a TIR for only part of the day seriously. This is the trap people fall into, Afrezza regulates my levels wonderfully, but if my levels are out of range at night that's 33% of the day so TIR has a hard cap at 67% assuming the daytime numbers are perfect (which they never are). Now if I am averaging 75% TIR with an AID pump which is the better option? That is the problem, nights matter. If you can't get past 67% that's nearly an extra two hours I am going to be out of range. Now I think you can do better than that but it will require changes to get there and exactly what those would be I don't know - higher doses would be a guess? The pump switch trial has TIR as a secondary goal (actually in a lot of different flavors!) Details here: clinicaltrials.gov/ct2/show/NCT05243628 |
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Post by agedhippie on Jun 15, 2023 19:37:21 GMT -5
There is no way anyone in the medical is going to take a TIR for only part of the day seriously. This is the trap people fall into, Afrezza regulates my levels wonderfully, but if my levels are out of range at night that's 33% of the day so TIR has a hard cap at 67% assuming the daytime numbers are perfect (which they never are). Now if I am averaging 75% TIR with an AID pump which is the better option? ... Now I'm feeling guilty. So here is how you fix the problem; do basal testing to make sure people have their basal properly set. If you are consistently going high at night then your basal needs adjusting. RAA has a longer tail so these errors are not as visible and you get pulled back into range, Afrezza has cleared so there is nothing to help. Fix that and you can get beyond the hard cap of 67%, don't fix it and you will stay capped. |
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Post by uvula on Jun 15, 2023 19:40:56 GMT -5
I'm not diabetic and not a doctor so I probably have no right to suggest this, but here goes. If basal dose is optimized for use with afrezza, and if a patient is not eating while sleeping, won't the patient stay in a good range while sleeping?
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Post by agedhippie on Jun 15, 2023 22:22:47 GMT -5
I'm not diabetic and not a doctor so I probably have no right to suggest this, but here goes. If basal dose is optimized for use with afrezza, and if a patient is not eating while sleeping, won't the patient stay in a good range while sleeping? With a pump yes, with a basal shot no. The problem is that basal glucose output varies throughout the night (and also the day and weather, but lets stick to nights) with a low point for a couple of hours around 2 or 3am. After that it increases and peaks around dawn (the dawn phenomena). If you size the basal shot to cover the peak you will go low during the dip. If you size the dose to avoid a low during the dip then you go high leading up to the peak. Usually you aim for a mid point and take your chances with the low. Pumps avoid this because they have basal profiles which you use to fit to the curve. AID pumps can dynamically vary the fit to the curve to get even tighter. |
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Post by uvula on Jun 16, 2023 7:18:03 GMT -5
Aged, thank you. A few years ago people here posted 24hr strip chart recorder graphs of how perfectly their blood glucose was controlled with just basal and afrezza. Your reply suggests that this is not possible overnight. I feel like I'm missing an important piece of the puzzle.
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Post by prcgorman2 on Jun 16, 2023 8:03:28 GMT -5
I think the point is that the basal slow-acting insulin ensures the person with diabetes has “insulin on board”. That’s critically important. What it doesn’t do is perfectly match the blood glucose requirements of the person with diabetes so the possibility of excursions outside of Time In Range increase. Excursions may not be guaranteed but they will be more likely depending upon the basal, the conversion from basal to usable insulin, the body’s production/consumption of glucose. And, that with a pump with a CGM feedback loop and algorithms to tune the application of basal, the excursions become less likely and Time In Range improves.
I think that is all well and good and outside the scope of what Afrezza can help with which is daytime, mealtime, insulin needs. It’s reasonable to say day and night are both important and to design the treatment accordingly.
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Post by sayhey24 on Jun 16, 2023 8:08:22 GMT -5
I'm not diabetic and not a doctor so I probably have no right to suggest this, but here goes. If basal dose is optimized for use with afrezza, and if a patient is not eating while sleeping, won't the patient stay in a good range while sleeping? With a pump yes, with a basal shot no. The problem is that basal glucose output varies throughout thwnight (and also the day and weather, but lets stick to nights) with a low point for a couple of hours around 2 or 3am. After that it increases and peaks around dawn (the dawn phenomena). If you size the basal shot to cover the peak you will go low during the dip. If you size the dose to avoid a low during the dip then you go high leading up to the peak. Usually you aim for a mid point and take your chances with the low. Pumps avoid this because they have basal profiles which you use to fit to the curve. AID pumps can dynamically vary the fit to the curve to get even tighter. For a T2 who is not so far gone and does not need the basal, no one cares about when they are sleeping. For afrezza, the big market is the T2s and the Medicare crowd is nearly half the market. This is not the pump market and if we get the T2 early enough most should never progress to needing the pump. In fact Bill says we should see reversal in some cases. If we can get the T2 below 140 within 2 hours after the meal thats the "TIR" we want. If we can get them in the 90-100 range, even better. If we can do that we will see the benefits Bill mentioned earlier. During the night will the BG rise, maybe a bit but who cares. When they wake they take a puff of afrezza with their coffee. You asked the question - "if a patient is not eating while sleeping, won't the patient stay in a good range while sleeping". The short answer is yes. For the T2 not on a basal there should be no issues when sleeping. For the T1 the real concern is going low because of the basal. For most this is not an issue with afrezza. Will the AID pump do better when sleeping, sure when they are sleeping but it will never match afrezza for meal time control. This is why Al developed afrezza and the CGM. He knew the issue was not the technology but that the RAA insulin was too damn slow. For the T1s, the battle between the AID and afrezza should be solved with the kids, once approved. If they are getting the control we expect and the moms feel good about their kids using afrezza, in the long run afrezza and basal will win. Few kids want to wear a pump and inhaling is cool. We will have to wait until next year to see how this starts playing out. For the T2s lets hope Mike got the Medicare pre auth requirement dropped for 2024. If so this opens lots of potential discussion with other vendors next week. |
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Post by agedhippie on Jun 16, 2023 8:25:06 GMT -5
For a T2 who is not so far gone and does not need the basal, no one cares about when they are sleeping.... More accurately, you don't care and believe others shouldn't. However, the medical world very much cares and since it's their world we are playing in that's what matters (also I happen to agree with the medical world on this one  ) |
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Post by uvula on Jun 16, 2023 8:25:08 GMT -5
Sayhey, you are simultaneously arguing that, for T1s, Afrezza+basal is better than an AID because of mealtime speed and an AID is better than Afrezza+basal because of nighttime control. Both can't be true.
The absolute best for T1s is probably AID+Afrezza.
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Post by agedhippie on Jun 16, 2023 8:26:00 GMT -5
Aged, thank you. A few years ago people here posted 24hr strip chart recorder graphs of how perfectly their blood glucose was controlled with just basal and afrezza. Your reply suggests that this is not possible overnight. I feel like I'm missing an important piece of the puzzle. The same way that people on RAA get the same results (see my earlier flatliner posts). Anything is possible if you put in enough work. The issue is what happens at scale because small groups are statistically suspect. Can I give this to hundreds of people and get that result - that would matter. Can I give this to a dozen people and get this result - that's interesting, but irrelevant without further work. This is why I hammer on about clinical trials, it's how you get endos to buy into Afrezza. |
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Post by sayhey24 on Jun 16, 2023 8:26:15 GMT -5
The problem is simply that BP no longer believes in inhaled insulin. They have seen two of their own fail (Pfizer and Sanofi), and eight years after launch Afrezza sales are a rounding error in the market. It's hard to emphasis how negligible the Afrezza market share. Take just Humalog (ignore Novolog and all the newer insulins) who had TRx 726.4k in May, Afrezza TRx was 3.8k. Afrezza undersold even Humulin R which nobody should be using at this point by 8:1. I think pediatrics has the potential to double Afrezza sales, but not much beyond that because endos are pushing AID pumps. That's my opinion, but it based on talking to several endos in the big NYC teaching hospitals (donate to hospital groups; (a) it helps the diabetes centers which are never profit generating, (b) it gets you access to people) I think it's likely correct. Mannkind owns Afrezza whether they want to or not so it's high time they did something about improving sales and that means large trials to get the data proving superior outcomes in various scenarios. Then you may see a partner emerge, but maybe you wouldn't want one at that point... The ole pesky chicken or the egg strikes again. I think the problem is Mike wants the "right deal". I know he has turned down offers. His issue is the shareholders have put over $3B into afrezza development and he wants the "proper" return for the shareholders. He understands the value of what he has even if he has struggled to figure out how to sell it. At this point things are turning in a very favorable position for afrezza so I think time is on our side. For the T1s the kids will either make or break the afrezza T1 market. IMO, they will make it regardless of the endos "pushing" pumps. I have gotten into my fair share of "discussions" with UPenn doctors. Of course they are not NYC. This is really going to be all about the moms and if afrezza is as good as its currently looking in the trial. If it is we should be in a great T1 position. For the T2s maybe we got lucky with the India trial and they properly dosed. If the 1.5-2.0% A1c reduction Mike mentioned is real and no CGMs were used, what could be realized if we added CGMs, remote monitoring and custom dosing? If Mike would get moving with the afrezza/Ozempic/Mounjaro trial he mentioned a few calls back I think between that and the India trial, that is the 1-2 punch we need. |
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Post by sayhey24 on Jun 16, 2023 8:34:05 GMT -5
Sayhey, you are simultaneously arguing that, for T1s, Afrezza+basal is better than an AID because of mealtime speed and an AID is better than Afrezza+basal because of nighttime control. Both can't be true. The absolute best for T1s is probably AID+Afrezza. Why not? Of course its true. afrezza is better than the AID at mealtime control and the AID is better than the basal when you are sleeping. If the T1 is pretty fragile and they don't have good nightime control they can wear the pump but who wants to wear a pump when you can realize "Bernstein" numbers without the effort? I believe Richard is 88 now so what he has been doing seems to work very well, atleast for him. Can afrezza and basal match his numbers without a pump? I say yes. BTW - if I remember correctly he got into a heated discussion over this exact topic with Al because Bernstein saw using afrezza as "cheating". |
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