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Post by agedhippie on Feb 13, 2023 13:57:52 GMT -5
The pump sounds cumbersome and technical… and has quality issues being addressed from a Legal safety standpoint… looks like if MIKES abc trails go well ,why would that combination not be a home run for The market he intends it for … regardless if it takes somewhat longer .. should be interesting. It's cumbersome, no doubt. However, the quality issues are overblown. The trade offs still make it appealing to a lot of people though. The ability to reduce what you have to do with your diabetes (or any chronic disease) is hugely underestimated here. In adding Afrezza to the mix you are asking people to do more with their diabetes and that's always a hard sell. Now there are always people who are prepared to take on more, Ginger for example who is taking Ozempic on top of everything else, but most are not.
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Post by agedhippie on Feb 13, 2023 11:50:15 GMT -5
Then what’s the ABC TRIAL for ? The trial is interesting, but will only be significant if they repeat it on a bigger scale. The current trail is really just a pilot. It's a comparison of Afrezza with Tresiba or a pump vs a pump. The protocol is unusual. The Tresiba + Afrezza is what you would expect with Tresiba as the basal and Afrezza for everything else. The Afrezza + pump uses the pump to provide the basal and Afrezza for meal times BUT the pump provides any follow on meal time insulin so the second dose for the meal will now be left to the pump and RAA. The pump is just the pump. The pumps are AID (automated Insulin Delivery) pumps so in theory they adjust to keep things level. Things to watch: - The two Medtronics pumps they are using are hardwired to a target of 120 so if you are at 100 the pump will raise your level. That has the potential to elevate BG levels (the later Medtronics pumps are adjustable). - The pumps can operate in automatic or manual mode. In automatic mode the pump can switch back to manual if it thinks it has lost track and that can result in higher numbers. The most interesting arm is the middle one. What it looks like they are doing is taking Afrezza for the meal and letting the pump clean up afterwards. How the pump handles that will be very interesting as the behavior is unexpected, but potentially you could take Afrezza for the meal not tell the pump and let the algorithm deal with the fallout. If that works you can just take Afrezza and let the pump clean up the rise you get after the first dose wears off.
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Post by agedhippie on Feb 13, 2023 9:56:15 GMT -5
Clinical trial results have shown that once-weekly basal insulins are just as effective at reducing A1C as once-daily insulin. In July 2022, Novo Nordisk announced the results of the ONWARDS 3 and ONWARDS 4 clinical trials, showing that icodec, a once-weekly basal insulin, was just as effective as once-daily insulin. Icodec There was a question earlier about who does early additional trials? This is the poster child. Onward-1 was the phase 3 trial, Onwards 2-6 are follow-on trials to expand the label and to draw a bright line between Icodec and the other basals. This is all before the drug is even approved. This is how the deep pocketed pharmas do it, it is not an option at this scale for the small pharmas but follow on trials are needed. The phase 3 trial (the point at which the FDA will approve the drug) essentially establishes that if taken as prescribed it's unlikely to kill the patients in large numbers, and that it's no worse than the alternatives. The subsequent trials establish why you should use the drug over the alternatives. If you stop after phase 3 you get the result we see with Afrezza which is not a reflection on the drug but rather that there is no data to show how good it is so the adoption rate is glacial.
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Post by agedhippie on Feb 13, 2023 9:44:03 GMT -5
Actually Tresiba is daily Thanks. Insert correct once weekly Oddly Tresiba isn't that far off the mark. Icodec is basically a version of Tresiba that binds more aggressively than Tresiba to the albumin so it lasts longer.
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Post by agedhippie on Feb 12, 2023 23:35:39 GMT -5
Most people I know avoid the Medtronics pumps, and my endo won't prescribe them. That said if there is a recall of 175,000 pumps for two models that's a lot of sales. There have been two recent problems with them; the broken retainer ring the recall refers to, and and earlier problem with it loading a blank profile if you upgraded from another pump. The thing is, do the benefits outweigh the risks? That's always the question and for a lot of diabetics the answer is yes. What is the benefit of the pump over 1 shot of tresiba and afrezza at meals? I keep seeing afrezza users saying they would never go back to the pump. Now I see Lane working with MNKD. What's that about? The benefit is that I don't need to watching my CGM and correcting, the pump does that for me, so I can spend less time bothering about my diabetes. With Afrezza I would need to take the Afrezza at mealtime, then I would need to monitor my CGM and quite possibly take another which isn't going to work if I am in meetings. That still leaves nights. I have no doubt that Afrezza can drop my level faster than the pump, but it also wears off faster if we look at STAT it takes two doses per meal. I would take the trade off (hypothetical because I don't currently use a pump) with tighter control from the pump over short term faster drop with Afrezza. Of course you hear some Afrezza users saying they would never go back, because they want others to repeat their success. You don't hear the rest because they don't post, there's nothing to say. It's why you cannot use anecdotal evidence in science - incomplete data sets. As to Lane, I have no idea what he is doing. My bet would be selling Mannkind modelling services for their FDA applications. You can read what Nudge BG sees as their mission - it's fully automated systems and Afrezza can never be that.
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Post by agedhippie on Feb 12, 2023 23:13:50 GMT -5
And to make it even more credible an observation, mike expressed interest in the last call. Tresiba Afrezza Tresiba = once weekly, Afrezza = mealtime control, Dexcom = Continuous Glucose Monitoring This is what Mike should be thinking. Actually Tresiba is daily
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Post by agedhippie on Feb 12, 2023 11:12:39 GMT -5
I just got two of these in my email. Most people I know avoid the Medtronics pumps, and my endo won't prescribe them. That said if there is a recall of 175,000 pumps for two models that's a lot of sales. There have been two recent problems with them; the broken retainer ring the recall refers to, and and earlier problem with it loading a blank profile if you upgraded from another pump. The thing is, do the benefits outweigh the risks? That's always the question and for a lot of diabetics the answer is yes.
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Post by agedhippie on Feb 12, 2023 11:01:13 GMT -5
Yeah. Those pumps are valuable because they are the ones the #WeAreNotWaiting community use for their APS work. That flaw allows you to take control of the pump and run your own controller. It drives the FDA into a frothing frenzy because, well, #WeAreNotWaiting for them. They have been trying to get those back for years, but at this point the pumps are so old that only the people who want them have them.
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Post by agedhippie on Feb 10, 2023 10:23:44 GMT -5
... I'm getting the idea that, depending on the results of the India T2 and the pediatric trials, "The Board" would like to build up a profitable endocrine segment and sell the whole unit to Novo, which he mentioned, or somebody. Could be hundreds of millions, could be billions depending on the results of the next year. What a war chest that would be for the orphan lung portfolio? I like keeping all the profits but if a company of size with the capabilities needed wants to pay up (big time) and promise not to shelf it, I don't know what do you guys think? India, Larger Pump switch trial, Pediatrics then decision time? And, what would a sale of afrezza look like? Is it a non-starter, we want to keep it? Sell then manufacture for them? Sell and collect royalties? Sell for BIG $ and no royalties? I think until UTHR Afrezza was the only path to profit so the Board had no choice but to stay with it. Now I suspect they would like to sell it since it seems that without a major investment in trials it's going to continue as now. Who they could sell it to is problematic. Lilly and Novo Nordisk aren't going to buy it because they are already heavily invested in the RAA and GLP-1 markets. Sanofi will not buy it for obvious reasons. Does anyone else want to compete with them? It's hard to see who. I expect them to keep Afrezza if they cannot get a good offer because when UTHR take over manufacture Afrezza will keep the manufacturing lines occupied between other molecules.
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Post by agedhippie on Feb 10, 2023 9:49:59 GMT -5
agedhippie - I don’t care how much shorts pay in interest to short MNKD, because I don’t know how much interest-free naked shorting goes on and don’t trust the companies who use that tactic. ... You should care, because in the same way that Symphony reflects the total sales although it's only a fraction the interest rate on loans reflects the activity in the dark pools. If nobody is shorting in dark pools, naked or otherwise, then the interest rate will be low because there is leakage between those realms (brokerages have visibility into both sides) TBH if you are in micro-caps like MNKD there is always manipulation, the only question is the degree. Right now I would expect it to be low because MNKD is relatively stable given the UTHR revenue stream.
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Post by agedhippie on Feb 9, 2023 18:26:30 GMT -5
Foe what it's worth; short interest increased again... $MNKD Short Interest 1/31/23: 34,320,392 Days to cover: 11 Short Interest 1/13/23: 32,805,775 Change: 1,514,617 I really don't know why people bother with this stuff, but if you care then you should look at the proper picture. The best guide is the price you will get for lending your shares and here is a useful site: companiesmarketcap.com/mannkind-corp/cost-to-borrow/#Entertainingly Mannkind is at the lower end of the range. You pay a lot more to short Novo Nordisk or Merck!
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Post by agedhippie on Feb 8, 2023 12:49:03 GMT -5
That is one of the reasons I invest rather than trade. I lack the situational awareness that the big boys have. It's rather like playing a field game and being the only one wearing blinkers.
Over the long term the advantage that the big boys have fades because their timescale varies between short term, and very short term. Nobody is big enough to fix a price in the long term, nor is it in their interest (again, that short term problem). Invest for the fundamentals, don't try and trade unless you enjoy gambling. Do that and dark pools don't matter.
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Post by agedhippie on Feb 6, 2023 23:45:31 GMT -5
You could be right but first they have to get Medicare approval. Do you think Merck, Nova Nordisk, Lilly and the rest want T2s using a CGM showing PPG excursions without the cover of a mealtime insulin??? They think they are getting approval by July and the NICE study is what they are banking on but this is the only study I see and its for T1s. www.nice.org.uk/guidance/ng17/evidence/b-continuous-glucose-monitoring-in-adults-with-type-1-diabetes-pdf-11013435182If you think the study I provided was the best and it starts off saying "Evidence supporting use of continuous glucose monitoring in type 2 diabetes treated with basal insulin is unclear" then I am not thinking this is a slam dunk but I think you are right and they do. For the first time I am rooting for the antiglycemic BPs squashing the approval but we will see by July. I thought public comment has ended. If not I will probably put something in. Man, I sure hope you are wrong that "getting the SoC changed is a nice idea, but unrealistic". That almost sounds like "You can't do that!". IDK, I am going to keep fighting the good fight. I don't think Merck etc. care about CGMs one way or the other. The SoC is what matters to them. There are a ton of papers in the references section of the LCD that Abbott submitted to the CMS (my earlier link). NICE isn't really relevant, you can think of them as the UK equivalent of the CMS and their role is to decide whether or not NHS trusts are allowed to buy a drug (the trusts still need to decide if they want to buy the drug after that). The line you quote, "Evidence supporting use of continuous glucose monitoring in type 2 diabetes treated with basal insulin is unclear" is from the introduction and is the justification for the paper. If the evidence was clear the paper would be redundant! You probably want to read the conclusion section in the abstract which is a solid yes for the approach; In a real-world retrospective USA study and a meta-analysis of a larger USA and Canada cohort, HbA1c significantly reduced in basal insulin-treated type 2 diabetes, without bolus insulin initiation and following the commencement of flash glucose monitoring technology.The rest of the evidence is equally solid. Abbott know what they are doing, it's not their first submission by any means. It's not that I don't think the SoC can be changed, how to do it is clearly outlined in the SoC itself, it's more that I don't see Mannkind having the inclination to spend the time and money to do the work. Does Mannkind even want to change the SoC, or would they be happy leaving things as they are if they could just get a bigger share of the market?
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Post by agedhippie on Feb 6, 2023 16:30:51 GMT -5
Thanks - I had looked at this earlier. While I think everyone should be able to get a CGM I think what they submitted does not show A1c reduction as a result of the CGM. Its because of adding the basal not the CGM. In the one study I think there was a little better reduction using the meter with the basal. Abbott wants to sell CGMs. I don't blame them. Will they succeed with the basal request, IDK. All I am saying is afrezza is $35 and meets the requirements for a CGM. Adding the afrezza has little chance of producing severe hypos which I would think is a much easy sell to the GPs. I think if Mike has not already talked to them he should. Would they be willing to fund a study I would think they would. They have already funded 5 for the basal. Am I inventing my own SoC with a Treat to Target protocol, I sure am. Did I invent it? No but before afrezza it would fail at PPG. Does T3 work? Yes it does but only with afrezza. Should existing large scale data already be available for this with afrezza? Yes it should but it does not because MNKD never did the study. Is there pilot data available? I think so as I think Al did at least one. Here is some crash and burn study info www.ncbi.nlm.nih.gov/pmc/articles/PMC3987265/Actually the link you gave earlier was the best evidence. They looked at basal users, not people who had previously not used basal insulin and they found a reduction. Another of the papers cited was the original Dexcom trial from back in 2011 and the first looking at, again, established basal users. Beyond that, the MOBILE trial, again existing basal users given a CGM. What was really interesting was what happened when they took away half the CGMs, people's TIR almost halved and their A1c rose. They have the evidence to support their case I feel (plus I think diabetics should be able to get CGMs if it would help). Abbott funding trials for Mannkind plus the costs of getting the SoC changed is a nice idea, but unrealistic. Abbott are already a long way down their current path and are not about to dump a multi-million dollar investment for a speculative venture that anyway will take longer than the current path. Once we rule out Abbott we are back to Mannkind doing the work. They need to do the trials to prove the theories and change the SoC, and until then nothing changes.
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Post by agedhippie on Feb 6, 2023 12:49:55 GMT -5
Aged - Is this one? - www.ncbi.nlm.nih.gov/pmc/articles/PMC8783803/"Evidence supporting use of continuous glucose monitoring in type 2 diabetes treated with basal insulin is unclear. This real-world study aimed to assess the impact on glycated hemoglobin (HbA1c) of flash glucose monitoring use in adults with type 2 diabetes managed with basal insulin" That was the observational trial, there are another four trials but I haven't looked at those. This is the LCD for the change: www.cms.gov/medicare-coverage-database/view/lcd.aspx?lcdid=39473&ver=16Search for the section "GM for beneficiaries with diabetes administering insulin 1-2 times daily". There are some references to papers and trials in there.
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