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Post by agedhippie on Jul 11, 2024 9:20:04 GMT -5
It looks like the FTC is about to sue the three biggest PBMs accusing them of illegal market manipulation in blocking generics. The insulin market got a special call out.
An example of what they are talking about is the use of branded rather than generic insulins. I had this recently with Tresiba. My doctor wrote the prescription for degludec rather than Tresiba. I don't care because they are both made by Novo Nordisk and literally the only difference is the label on the pen. Caremark would not fill the prescription because while they cover Tresiba they don't cover the generic. The generic is 1/3rd the price of Tresiba so it cuts into Caremark's profits and raises my co-pay.
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Post by agedhippie on Jul 10, 2024 9:46:48 GMT -5
I remember Al saying in an interview he would take Afrezza with the meal or a few minutes (5 I think?) into the meal. I never remember the details of what triggers the pancreas to squirt some insulin into the bloodstream at mealtime but I’ve assumed something will trigger a follow-up squirt later as needed. I assume the 2nd pancreas bolus isn’t finely tuned to only the exact right amount of insulin, so it may be something like whatever’s accumulated after the meal gets released and the liver and other stuff takes care of the rest of the work of moderating blood sugar post-meal. The equivalent with Afrezza would be to take a bigger dose with the meal and perhaps a smaller dose afterwards if needed. I get that’s a hassle for folks who would really prefer to not have to keep after their diabetes so compliance may (will?) suffer some, but for patients who can afford it and tolerate Afrezza well, it could beat the living daylights out of roller-coaster RAA. agedhippie - did I correctly understand INHALE-3 trial showed Afrezza is safer for avoiding severe hypoglycemia? Insulin is release in five or so phases with the initial phase being before the meal starts when you are thinking about food (see mouth-watering ) The phase 2 release is actually better tuned to the amount of insulin required because it is a continuous release modulated by the glucose and insulin levels in the blood. What it lacks is the volume that is provided by the first phase. Think of it like a cistern with the initial release and then a steady flow. The whole thing is controlled by the ATP channel and polarization/depolarization of the channel membranes. I confess that the detailed mechanism is far to complicated for me to understand and I always get lost but I think that is basically right. The only reference I could find on severe hypoglycemia was that there was one in the Afrezza group and none in the usual care group. There was one DKA case in the usual care group (I suspect a pump). Hypoglycemia in general was the same across all groups. " As for safety, 77% of those in the technosphere insulin group experienced adverse events (AEs), with only 1 severe hypoglycemia even, and 64% in the usual care group experienced AEs with 1 experiencing hospitalization for hyperglycemia/ketosis and 1 for appendectomy." I would expect the primary AE for Afrezza to be cough so nothing I really care about.
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Post by agedhippie on Jul 8, 2024 17:16:35 GMT -5
Aged, it's interesting to hear you talk about your experience, and your admission that after a couple of months you would be likely to get a little careless with a regimen of Afrezza. Thanks for your honesty and your contributions. You often mention follow up doses. I wonder how much follow up dosing the really astute users of Afrezza do. Are they able to adjust the timing of the dose, and the size of the dose so that follow ups are rare? I'd be interested to know. We had a little excitement here when my recently diagnosed 8 y/o granddaughter jumped in the lake with her pump on and her phone in her pocket. My son watched her do it and didn't stop her. When my DIL figured out what was going on there was a little hell to pay. But all was corrected (by my savvy DIL) and my GD got to spend plenty of time in the lake without her pump. My wife and I are very careful not to interfere and proselytize about Afrezza, and to let the family and their endo chart my GD's course. She's doing well with the pump, but I will be surprised if in 5 or 10 years she doesn't ditch it for Afrezza, which she wouldn't have to wear 24/7. But who knows? As you say, it's not one size fits all. I have wondered if you can dose really late with Afrezza, maybe 30 minutes after the meal, and shift the window far enough to cover the tail at the cost of rising further initially. If your GD wants to swim in the lake then she needs an Omnipod as I don't think any other pump is rated for that. Removing the pump (and phone!) is definitely a good idea. I suspect once she gets to her early teens she will want to get rid of the pump, but then you have the fun of getting her to take her insulin rather than having the pump do it. The key there is getting her to do it without traumatizing her. Pre-pump they used to do it by threatening you with all sorts of nasty complications and an early death. Unsurprisingly that led to mental health issues.
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Post by agedhippie on Jul 8, 2024 16:48:45 GMT -5
... Spending the money on an afrezza/glp1 study would be money much better spent than chasing another head fake like V-Go. I am also sure MNKD-101 and 201 are not taking up that much of his day on a daily basis. If he can't oversee the MNKD-101 and 201 development while getting afrezza insurance coverage, "Houston - we have a problem". Arguing that it would be superior if only everyone dosed properly is just going to get you eyerolls because doctors know that never happens. There is nothing Mike can do to expedite insurance cover at this point so he would be wasting time trying. The insurers are just going to point to the A1c result and claim equivalence. Mike is far better off focusing on the pipeline where there are real prospects.
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Post by agedhippie on Jul 8, 2024 8:20:15 GMT -5
... If you think insurance companies are going to point to the 7.6% A1C then Mike has 6 months to fix that. That is his #1 job. There is no mystery here. Those that did not get the great numbers are not properly dosing according to the "All Star" team which presented the results. With connected care that is not really that hard to fix. They need to be txting and calling these people. They can see exactly when they are dosing and when they are not from the real-time CGM reports. If everyone of these people needs a personal coach then Mike needs to get them one. ... People not dosing properly is a fact of life and why large scale trials matter. That is incredibly hard to fix. You cannot hire coaches because it's not in the protocol. More importantly the doctors are going to ask if the only way Afrezza works is if every patient has a coach because that will not scale. As for texting and calling my suspicion is that number will be blocked instantly, nobody likes being harassed. It is not possible to see what people are dosing unless they are using Bluhale, and even then probably not because you don't know what they ate.
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Post by agedhippie on Jul 7, 2024 15:30:14 GMT -5
INHALE-3 still only managed non-inferior. Insurance decision are justified as outcome based and the outcome has not changed. What change are you expecting from the SoC that will force insurance cover? ... You ask - my expectations for the SoC? Mike has to get insurance coverage and I don't really care how he does it. His #1 job right now is to get insurance coverage before pediatric approval. What ever he needs to do to get the proper words put in the SoC to help get the coverage and promoted expanded scripts is my expectation. The problem is this - At 17 weeks, technosphere insulin was noninferior to usual care, with the technosphere insulin group having an HbA1c of 7.6% and the usual care group having a 7.5% HbA1c (P = .01 for noninferiority). Insurers will argue that RAA and Afrezza deliver the same outcome and therefore there is no reason for them to cover Afrezza since they cover RAA. That's a show stopper - how does Mike get around that?
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Post by agedhippie on Jul 7, 2024 9:52:47 GMT -5
In the Juicebox podcast Mike Castagna mentioned that he was frequently asked about a 2U Afrezza cartridge (and remembering that 2U of Afrezza might be equivalent to 1U of insulin) and his first question is why would you want that? And his follow up is, are you (the person asking) using an AID pump? He said the answer was invariably yes to the AID pump. I thought that was interesting because the discussion on the board here had been a smaller than 4U cartridge would most likely benefit young T1s. Listening to the host and Mike describe how hard it is to wrestle with keeping blood glucose in range, it made me wonder if there is a market for an extra small cartridge for AID users and potentially young T1s. AID pumps use small doses because they dose frequently. The Tandem t:slim X2 doses every 5 minutes. By using very small doses (micro-dosing) they can curve fit better. It's the same way that when you drive you continually adjust your steering rather than sudden wrenching the wheel around at the last minute. If someone is asking about 2u cartridges they are probably looking for very tight control and care about the change that 2u will give them - for most of us it's more work than we are willing to do. Young T1s will benefit from small cartridges because they are more insulin sensitive (the start point is usually taken as 1:50 rather than 1:30 for adults) as they have very low bodyweight. Realistically though if the panel was right about Afrezza having a 2.8:1 ratio then a 4u Afrezza cartridge is just under 1.5u of RAA which looks good enough to cover that use case.
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Post by agedhippie on Jul 7, 2024 8:43:09 GMT -5
What is we get trial results merely inline with expectations, and Mike doesn't kick of Afrezza/GLP1 study? The expectation is the kids get approved. The expectation is Mike can take the Inhale-3 results and get SoC changes to justify insurance coverage. ... INHALE-3 still only managed non-inferior. Insurance decision are justified as outcome based and the outcome has not changed. What change are you expecting from the SoC that will force insurance cover?
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Post by agedhippie on Jul 7, 2024 8:22:55 GMT -5
Aged, what if there was a larger dose of Afrezza you could take that could potentially curtail the need for a follow up? Is a follow up the main reason why you wouldn’t start Afrezza? I wonder what percentage of VDex patients need follow ups? And what percentage take large doses into a meal and avoid needing one? I remember Bill always talking about waiting a while into the meal before taking the initial dose because it works so fast. Are people in the INHALE-3 trial taking their Afrezza too soon? Not having to follow up would definitely make Afrezza an option. Combined with the absorption pattern I would try that. It would need a bigger cartridge though as I usually take around 10u to 14u for a meal which would probably mean three cartridges based on the ADA comments (2.8 to 3x). I can see the large dose working to a degree, but depending on the composition of the meal you just ate. As an extreme example there is no way you could cover pizza with that approach because of the fat. On the other hand a meal with a lot of processed carbs may work. If it was me I would probably bolus at the end of the meal because I think that Afrezza is fast enough to outrun my digestion and the delay would give a better outcome.
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Post by agedhippie on Jul 4, 2024 23:41:38 GMT -5
When I listened to the Juicebox podcast what struck me most was the difficulty imposed by the variability of living with diabetes in administration, absorption, and action over time of especially RAA insulin which makes stacking a nightmare. I used to think inhale a cartridge of Afrezza and it will eliminate a stubborn high, and you’re right as rain. But listening to the podcast I realized its not that simple. Afrezza is good about in and out fast, but if used in combination with an RAA and the RAA (or body reaction) kicked in, then a low could be on the way. No free lunch as it were. Are basal insulins as variable as RAA? Or are they better at maintaining a more constant background amount of insulin for a day? If they’re more predictable, it would seem like basal + CGM + Afrezza could make life less complicated. Basal tends to be more stable which is a problem all of it's own. You basal needs fluctuate throughout the day being high in the morning and low around 2am at night. On a pump you usually have profiles that fit that curve. The belief that diabetes is mechanistic is the bane of a Type 1 diabetics life. Your endo will happily accuse you of lying (in a nice way) if they see something that doesn't fit what they expect, but you can literally eat the same meal two days in a row with different results depending on what you ate for the previous meal, or what your level was when you ate, or even the weather.
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Post by agedhippie on Jul 4, 2024 16:19:42 GMT -5
I don’t really understand your comment about being able to “sustain” using Afrezza. But I’m sure its because I don’t understand how you assume you would use Afrezza. Maybe sustain is the wrong word but I think it fits. Could I take Afrezza every time I was supposed to? Over a burst of a couple of months I could probably do that, but over a lifetime I couldn't sustain that. I would start start skipping the follow up doses, snack and not dose, that sort of thing. My endo knows he could put me on a program that today that would markedly improve my A1c, but he also know that after a couple of months I would fail so he doesn't go down that path - don't set patients up for failure.
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Post by agedhippie on Jul 4, 2024 13:54:45 GMT -5
That is an interesting article, especially for the comments from the panel. This quote from Irl Hirsch in particular; “Somebody who is coming in with an [Hb]A1c above 7%, what we showed was that the inhaled insulin did better than the MDI in general, but not as well as the AID, but I still think the more important point of the whole thing is that depending on the patient, and their personality, and their phenotype, and their engagement, we had all of these AID people who actually did better,” Irl Hirsch, MD, professor of Medicine and Diabetes Treatment and Teaching Chair at the University of Washington, said in an interview with Pharmacy Times®."Lets unpack that. If you are on MDI and want to stay on MDI you should probably switch to Afrezza (" inhaled insulin did better than the MDI in general"), but if you are on an AID pump you probably should not switch (" but not as well as the AID"). But for me the important line was the one that followed that and is often overlooked in these discussions (" but I still think the more important point of the whole thing is that depending on the patient, and their personality, and their phenotype, and their engagement"). One size does not fit all. Endos like the KOLs understand one size does not fit all and the treatment needs to reflect that because anything involving lifestyle changes is probably a non-starter. To give a personal example; I am still on pens, and since lockdown I have got pretty slack with dosing which my A1c reflects. Consequently my endo wants to put me on an AID pump so it does the work I am slacking on and my A1c will improve. I don't like the idea but ultimately it is where I am heading because getting back into my pre-lockdown routine is never going to happen. In abstract would Afrezza work for me? Yes. In reality would I be able to sustain it? Not a bat in hells chance. To Irl Hirsch's point - personality and engagement. So what is the good news here? The good news is that more people will be given the option to try Afrezza because there is now data that says it works so endos will at least try it. Will the patients all stay on Afrezza? Some probably not for the reasons Irl Hirsch gave, and because of insurance cover, but at the end of the day a much bigger pool has just opened up with Afrezza becoming a serious option.
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Post by agedhippie on Jul 3, 2024 13:21:51 GMT -5
Maybe you missed my earlier comment and/or you just don't understand.... More subjects utilizing inhaled insulin achieved glycemic targets: 30% of inhaled insulin group reached <7% (HbA1c) at 17 weeks vs. 17% of the usual care group 30% vs 17% is a 76% improvement over usual care group. (13÷17) 21% of inhaled insulin group vs. 0% of usual care group met A1c goal of <7% if baseline was >7% 21% vs 0% over the usual care group! 24% of the Afrezza group and 13% of the usual care group achieved TIR above 70% with no increased hypoglycemia in the inhaled insulin group. 24% vs 13% is an 86% improvement over the usual care group (11÷13). Conclusion - Inhaled insulin to treat Type 1 diabetes is superior to usual care treatments. To be clear on this; I think the results are ok, but for me the important thing is who they had on stage talking about Afrezza. That is going to be far more influential than the results we have seen so far. As an example take this metric: 21% of inhaled insulin group vs. 0% of usual care group met A1c goal of <7% if baseline was >7%.My initial reaction was wow. Then I thought about it a bit more. You would not expect any change from the usual care group by definition - they are not changing anything from what they have been doing. That 21% of the Afrezza group got below 7% is great, that 0% of the controls did was expected and would have raised question if it had been different. And we can sort of see that in this metric: 30% of inhaled insulin group reached <7% (HbA1c) at 17 weeks vs. 17% of the usual care groupIf you take those two together you see that 17% of the usual care group were already below 7% at the start of the trial (0% moved below 7% and 17% ended below 7%) The missing detail is the numbers for patients on MDI and patients on AID in the usual care group that fall into each group. I would be willing to bet that the AID group did well and the MDI group did badly dragging down the usual care group, but without the data we don't know. There is one metric that always gets skipped; 26% of the patients in the inhaled insulin group had a worsening of HbA1c greater than 0.5% compared with 3% with standard care. Again pretty much what I would expect on the control side with 3% being essentially flat, but 26% of Afrezza users got markedly worse? The nett of it is that this was a good day for Afrezza because you had a panel of KOLs saying they liked Afrezza. What all the panel emphasized though was that it's not a magic bullet - it will work well for some but not other making it a matter of matching patients to options.
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Post by agedhippie on Jul 2, 2024 6:57:08 GMT -5
Liquidia does not have the right to ILD…Please explain to me how Liquidia trying to “bundle” with their approval goes with the FDAs own rules regarding this. I am curious why you think LQDA doesn't have a right to ILD as the exclusivity period the FDA granted UTHR has now expired. As for explaining why the FDA and LQDA did not break the rules the best idea is for you to read the FDA response to UTHR's reply in the motion to dismiss the suit as it is explained in detail. For the curious with more time than is good for them here is a link to the whole docket: www.courtlistener.com/docket/68267106/united-therapeutics-corporation-v-food-and-drug-administration/
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Post by agedhippie on Jul 1, 2024 16:36:38 GMT -5
The FDA and LQDA filed a motion to dismiss the UTHR / FDA lawsuit this week. UTHR have responded, and the FDA and LQDA filed their response to UTHR this week. Main argument is that the UTHR action is speculative since the FDA have not approved anything (this was the argument they used to defeat the UTHR injunction). My guess, and it is just a guess, is that FDA want to see if they can get the case dismissed before approval as that would be cleaner. However, I think if it isn't dismissed the FDA will move to approve anyway because at that point they have no reason to delay further. As to timeline, it's in the lap of the judge! I should have been a bit clearer on this. I don't think the FDA win their dismissal (getting a case dismissed is always a stretch), but I think the FDA will approve regardless after the motion to dismiss is ruled. It's just that through choice they would rather have the dismissal as it would be cleaner.
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