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Post by agedhippie on Jun 22, 2023 9:19:14 GMT -5
Yes, that's a viable sized trial. This is exactly the sort of trial that needs to be done to address the Type 1 market. The only thing I would say is that they should pick a target rather than " using MDI, an automated insulin delivery (AID) system, or a pump without automation" because that leaves open the question of how much the MDI dragged down the whole arm and how Afrezza would have done against the AID pumps. The risk is that the non-Afrezza arm gets fragmented and the fragment size becomes to small. Is it too late to change the target? i.e., do adjustments such as you suggest get made to trials as they're getting started? Is that kind of change trivial or does it introduce complications? They can adjust the proportions in the recruitment phase. There are no fixed numbers quoted within the arm.
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Post by agedhippie on Jun 22, 2023 9:17:37 GMT -5
How long does this take? Two years to get results published and available to the public? More or less. It takes a while to recruit that number of people. There are companies that specialize in logistics including recruitment for trials, that's Jaeb Center for Health Research. The most interesting thing for me is that Irl Hirsch is the study chair so his name will be on the paper. Given his status in the medical research field this more or less guarantees publication in Diabetes Care, and that the paper will get read. I could see this as a possible 2025 ADA paper (trial ends October 2024 + 6 months for the QC approval lands just about perfectly.)
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Post by agedhippie on Jun 22, 2023 9:01:12 GMT -5
Nice. Is 120 patients enough to move the needle? Excellent question. I’m curious to learn agedhippie view on your question. ... Yes, that's a viable sized trial. This is exactly the sort of trial that needs to be done to address the Type 1 market. The only thing I would say is that they should pick a target rather than " using MDI, an automated insulin delivery (AID) system, or a pump without automation" because that leaves open the question of how much the MDI dragged down the whole arm and how Afrezza would have done against the AID pumps. The risk is that the non-Afrezza arm gets fragmented and the fragment size becomes to small.
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Post by agedhippie on Jun 21, 2023 11:36:16 GMT -5
I disagree wholeheartedly. As my pcp said to me, "We doctors have all been trained that prescribing insulin can only be the last resort because of safety. I would never prescribe insulin unless it's the last resort because of the possibility of hypos, emergency room or death". Once approved for pediatrics, the safety of prescribing human insulin with Afrezza will not only be huge news in the diabetes world but sales reps will be able to share this. It flips what doctors have been taught. Such news won't be confined to those only interested in pediatrics. IMO, this will be a huge game changer. So much so, it wouldn't be surprising to learn a BP is waiting on the approval to do a deal. I look forward to seeing what happens and my expectations are high. We'll see. The experience I have had to date with PCPs matches yours, they really don't want to prescribe insulin. PCPs are comfortable with metformin but the ones I used to talk to tended to think once it got beyond that that you should be seeing an endo. Kids have been on insulin since it was discovered so I am not sure why approving another one will change much in the adult space.
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Post by agedhippie on Jun 21, 2023 9:48:06 GMT -5
Pediatric approval is the golden ticket that will finally send the message to endos and pcps that the Afrezza method of human insulin delivery is very safe...and convenient, and easy to use, and eliminates or reduces meal-time spikes, and doesn't require a pump, and improves quality of life! I would be careful about expectations from the pediatrics trial. It's not going to change views, but what it will do is allow doctors to prescribe Afrezza for kids without going off-label. The numbers for adults have been available for years, pediatrics is treated as a different class (it's why there are separate adult and pediatric trials), so I don't see significant change in the adult market. If this is to change it's going to take trial data. Absent that we are trimming around the edges but not going anywhere.
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Post by agedhippie on Jun 19, 2023 11:02:02 GMT -5
Is Retatrutide a "oral" or sbuq drug? "Pfizer CEO Albert Bourla, Ph.D., sees his company being able to compete in a major GLP-1 diabetes and obesity market he believes will be dominated by a need for oral drugs" www.fiercepharma.com/marketing/pfizer-ceo-talks-experimental-oral-glp-1-diabetesobesity-hopeful-90b-lilly-novo-battleI am pretty sure Albert said he believes it to be a $90B market, if its oral. Sure lets focus on Clofazimine and not try and partner to get a piece of this market. Maybe a puff before each meal could get a piece of the market. I still have dreams of Mike picking up his new phone and trying to use it. It's subq. I take all numbers with a pinch of salt. Independent researchers put the GLP-1 market at $50B by 2028. The truth is nobody know and the Pfizer number is their aim for the total market size - but sometimes that market size doesn't pan out (Exubera.) The issue for the oral market is that it doesn't work as well, and it is the previous generation - GLP-1 only. That doesn't mean nobody is chasing it, Novo Nordisk has Rybelsus already on sale, Lilly has orforglipron just exiting phase 2 (this is the one Pfizer is targeting as the competition), and Pfizer has two and it's not sure which to push but neither will hit phase 3 before 2024 at the earliest. None of them come near Retatrutide for weight loss though. As an aside, what is the Pfizer CEO meant to say about GLP-1? We completely screwed the pooch and don't have a GLP-1 on the market? No, switch the message to oral and talk that up - those healthcare conferences are sales pitches to investors and he doesn't have any options.
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Post by agedhippie on Jun 18, 2023 9:38:44 GMT -5
An ADA related post! (It overlaps into GLP-1...)
One of the big announcements at ADA 83 will be the Phase 2 trial readout from Lilly's retatrutide drug which is the evolution of Mounjaro. Retatrutide is a triple therapy made up of GLP-1/GIP/glucagon. This is the arms race, and why Mannkind is better off with Technosphere and farming royalties. There is scope for the development work to replaform some drugs (Clofazimine for example), but the big markets like GLP-1 would be a money pit because MNKD cannot fund the development needed to compete.
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Post by agedhippie on Jun 18, 2023 9:21:19 GMT -5
... If we have "No" pre auths requirement in 2024 Medicare maybe we can get some help lobbying the ADA as a few companies want to sell CGMs to T2s. The CGM companies won their change! There is no incentive for them to lobby the CMS because they already have what they want, CGM use with the earliest possible insulin use (basal). Pushing Afrezza before basal would gain them nothing since they would sell a CGM either way.
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Post by agedhippie on Jun 17, 2023 8:13:09 GMT -5
And I always called it (CGM) the lie detector test ! If it’s as accurate as it’s supposed .. I can’t believe these conversations Aren’t to a point of more understanding… I know it’s a complex subject but it’s mostly all in the numbers.that you can’t argue With . There is no evidence from CGMs to support the idea that the overnight numbers are flat for diabetics, and that would have been huge news. Yet here we are over a decade after CGMs became widely available and nobody has noticed! TBH you don't even need a CGM, just a meter reading last thing at night and first thing in the morning.
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Post by agedhippie on Jun 16, 2023 21:46:53 GMT -5
I don't know why you keep saying that - it's flatly wrong. The testing for elevated glucose levels on waking is literally the test for pre-diabetes (and diabetes). ... If you are diabetic and went to bed at 90 because afrezza got you there by handling the post prandial spike, you are going to be around 90 when you wake. The pancreas for the T2 will handle the fasting state if you properly handle the prandial state. Sorry, that is still medically incorrect.
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Post by agedhippie on Jun 16, 2023 14:24:25 GMT -5
As a T2 diabetic your pancreas will provide enough insulin for the fasting state. I don't know why you keep saying that - it's flatly wrong. The testing for elevated glucose levels on waking is literally the test for pre-diabetes (and diabetes).
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Post by agedhippie on Jun 16, 2023 9:55:17 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. STAT-1 trial gave a TIR of 62.5% for Afrezza + basal, the Medtronics 780g (an AID pump) real world data for 4000+ people ( www.ncbi.nlm.nih.gov/pmc/articles/PMC8817690/) gave a TIR of 76.2%. Afrezza + basal needs to get to that ballpark number or endos will keep prescribing pumps. As an aside Medtronics is a good example of what Mannkind should be doing - gathering data and publishing.
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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 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 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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