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Post by agedhippie on Jul 27, 2024 18:14:39 GMT -5
...There needs to be 100% focus on getting insurance coverage for afrezza. MNKD-101, 201 and the rest are years away and at this point a pipe dream. Afrezza insurance needs to be 100% of the focus. Get afrezza insurance and we have $20pps+.... Easier said than done. Novo Nordisk and Eli Lilly own the GLP-1 market with some stunningly expensive, and hence very profitable for the PBMs, drugs. Why are insurers going to give up those juicy margins to make a huge loss selling Afrezza at $35 a month for all you can eat? Commercially, selling Afrezza would be a disaster for insurers, and reducing the price to where Afrezza is competitive would be a disaster for MNKD. You are going to have to compensate the PBMs for the margin they are losing on GLP-1 as well as making $35 per month prescriptions viable.
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Post by agedhippie on Jul 27, 2024 14:02:24 GMT -5
OK - so why didn't they take the bedtime dose? They agreed to taking the "correction" doses when they signed up and then didn't take them. Why? ... They didn't want to, they didn't feel they needed it, they had other things to do. There are any number of reasons. It's easy to forget that diabetics are people and not automata (endos certainly do from time to time). The trial will publish the results in line with registered study plan so cherry picking the results is not going to work. It's possible to do an analysis of just the compliant patients, STAT-1 did that in one paper, but the medical world is going to be looking at the headline figure as you can see from the ADA panel.
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Post by agedhippie on Jul 16, 2024 11:01:46 GMT -5
Aged, is it possible to take a guess here as to how this impacts LQDA's timeline? Minimum 3 months delay? Maximum delay =? Best case for LQDA, I don't see how they have any market penetration in 2024. Worst case, how far does this go in 2025? Let's have the disclaimer up front - I am not a lawyer, and in particular not a Supreme Court lawyer. Happily the process here is well defined and boils down to this: - UTHR files a request - The court requests LQDA replies within 30 days (this is where the August 30th date comes from) - The court then asks UTHR for a rebuttal withing 30 days (UTHR can request a 30 day extension which it would likely get, extensions beyond that are harder) - These briefing get rolled up into a conference where the justices decide which cases they will take. (I think I saw Late September mentioned as a likely date) - Any justice can request that a case is put on the discuss list. If no justice wants to discuss a case it dies here. - Once the case makes it to the discuss list then at least four of the justices must vote to accept the case, if not it dies here. - If they decide to accept the case the you are off to the races. The vast majority of cases never make it onto the discuss list and die there, so probably September/October. They only take about 80 cases per year. They can remand the case back to the lower court via GVR. This is possible because of the Loper Bright case, but I think that case is sufficiently different for it not to apply. This is why the LQDA share price hardly budged, what has happened so far is exactly what the process says should happen so there are no surprises. The most likely outcome is that this dies in the Supreme Court at the discuss list stage, but with this Supreme Court who knows! Where do I get all of this from? Mostly some friends who are lawyers, and from this: www.citizen.org/wp-content/uploads/opposingcertguide-1.pdf
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Post by agedhippie on Jul 15, 2024 16:43:05 GMT -5
Wow, so the Federal Circuit Court judges erred and went beyond the scope of the complaint to apply prior court decisions, without properly hearing the evidence as 'de novo' (when a court hears a case “de novo,” it is deciding the issues without reference to any legal conclusion or assumption made by the previous court) and thus violated the plaintiffs rights to a fair trial based solely and only on the facts of the new arguments. Long story short, the courts went beyond the scope of their judicial authority. This isn't going to be a problem just for LQDA. What the Supreme Court may do here is change the rules and that is going to hit all the Federal Circuit patent judgements. The patent cycle could become even more of a mess than it is already.
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Post by agedhippie on Jul 15, 2024 16:29:28 GMT -5
The article posted ealier today indicated the Supreme Court "long conference" in September is when the court may remand the case back to the circuit court. If the case is remanded, I have no idea how long it takes to conduct the "further proceedings". This will be a good topic to ask agedhippie about. Agedhippie has no idea!
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Post by agedhippie on Jul 12, 2024 17:06:37 GMT -5
"and corrections" - I don't make this stuff up. They were instructed to take a correction prior to bed according to several presenters. They did not take that correction. You can argue they followed the protocol but its clear from the CGM reports and presenters they did not take the correction. ... Taking a correction is discretionary. Bottom line? This line of argument will get you nowhere with the clinical trial and the results will stand.
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Post by agedhippie on Jul 12, 2024 14:46:02 GMT -5
... The question to be answered is why did these Inhale-3 participants intentionally not follow the protocol. Thats what I would like to hear more on plus what is Mike going to do about it. Are they properly dosing now for the October results? They better be. Protocol says: The Afrezza-Degludec group will inhale Afrezza at meals and corrections and will inject insulin degludec once a day for the 17 weeks of the RCT Phase.The requirement on them is that they take Afrezza at meal times, and if decide they need a correction they use Afrezza to make the correction. That's it, that's the protocol. Your argument is that they are not following YOUR protocol. Unless altered dosing is explicitly mentioned (which it isn't, see protocol) dosing follows the label.
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Post by agedhippie on Jul 12, 2024 12:24:43 GMT -5
Turning off the pump for their basal needs when they are sleeping would be fatal? I doubt that if they go to bed at 150. What it would do is jack up their A1c. No one doubts human insulin works in the real world. It works. This was a dosing study to show with proper dosing is afrezza as good as standard care. ... If you think turning off basal insulin overnight would not be fatal you don't understand how Type 1 works. If there is no insulin you will go into DKA and die, it's as simple as that - look up diabetic ketoacidosis. I know a person who died like that (pump occlusion and no CGM to alert). I think I understand your confusion now. This is not a dosing study, this is an A:B comparison between Afrezza and usual care. If it was a dosing study the whole thing could have stopped with the meal challenge.
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Post by agedhippie on Jul 12, 2024 9:58:03 GMT -5
... What if the doctors at the testing center told the AID people to turn off their AID at bedtime? How should we handle this? Do you see what you are saying? We should just accept this as the world of clinical trials? I am assuming that you mean the closed loop function rather than the AID pump itself (turning off the pump would be fatal). The short answer is that the patient would likely ignore the doctor. The world is not made up of ideal patients and until it is the trial process will not change - they need to know if the drug works in the real world and for what groups since one size does not fit all.
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Post by agedhippie on Jul 12, 2024 8:39:49 GMT -5
... In daily life it is what it is but this study is to determine if when using a specific protocol afrezza is as good/better than MDI/AID. What we see is when the protocol is followed afrezza wins and wins by a lot. When we add in people not following a major step in the protocol afrezza average down to non-inferior. ... Welcome to the world of clinical trials. You might not like it but this is how trials are run and the results will be based on this and not an idealized world.
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Post by agedhippie on Jul 12, 2024 8:30:23 GMT -5
A plan to make people remember better or feel like doing something they don’t feel like doing? Pay them! Some trials you get paid to participate, I don't know if this is one. All of them you get free supplies for the trial so insulin, CGMs, etc. are covered for free.
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Post by agedhippie on Jul 11, 2024 19:43:40 GMT -5
If they are not following the study protocol I would think you could not count their numbers. The were non-compliant. Before CGM reports it was not possible but now we know when they dosed and when they did not. What we don't know is why they did not follow protocol. We do know we have some presenters saying these people did not follow protocol. Adding results of people who for whatever reason intentionally did not follow the protocol would be improperly representing the study. Removing their numbers would make all the sense in the world. Since widespread CGM adoption, I have never really heard of anyone complaining about follow-up dosing afrezza. I have never heard it to be a problem. I have heard many people saying they were never told to follow-up dose. In Stat-1 afrezza kicked ass with post prandial results but dosing before bed was not part of the protocol. They do follow protocol, they don't follow it perfectly. Notice that the panel were in no way surprised that there was variability in how well people followed protocol. You can complain about this as much as you want, but when the results came out everyone will be in it and those will be the results the endos care about. If nobody is complaining about follow up dosing with Afrezza there shouldn't be a problem, and yet here we are.... Everyone will have been told to take follow up doses, they even tell RAA users to take follow up doses, likewise insulin at bed time (which I do every day). The fact that so few people do is a compliance problem, not ignorance.
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Post by agedhippie on Jul 11, 2024 19:22:18 GMT -5
From what I’ve read, compliance is a huge problem but it isn’t unique to Afrezza or diabetes. Compliance is a problem with every drugs. Sometime listen to doctors complaining about patients and blood pressure drugs...
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Post by agedhippie on Jul 11, 2024 16:06:49 GMT -5
... MNKD needs to figure out what they are going to do with those in the study who are not properly dosing. Why are they not properly dosing? Can they be put in a separate category so we only count those that properly dosed? With the CGMs they could not hide the fact they were not following dosing protocol. We heard it from some of the presenters. If their numbers can be removed from the overall A1c average - afrezza wins and will be superior. I say we will have to wait until after October to see how Mike and team addresses this. Trials are trials, you don't get to cherry pick just the results you want. Compliance, especially second doses, has always been a problem for Afrezza and we saw that clearly in STAT-1 trial results. While it is possible in subsequent papers to split out the compliant and non-compliant members (as in the STAT-1 paper) but you cannot do that in the trial itself because you would never get the protocol approved. The trial is meant to mirror real life and real patients so you are stuck with what you have.
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Post by agedhippie on Jul 11, 2024 11:36:04 GMT -5
The whole Non-Inferior versus Superiority discussion out of the Inhale 3 interim results publication had me struggling to understand how that whole process worked. I finally found a link that may help those wondering whether MNKD can claim Superiority based on the interim Inhale-3 results. www.ncbi.nlm.nih.gov/pmc/articles/PMC5472861/Pulled from the article...... "...Background
Current regulatory guidance and practice of non-inferiority trials are asymmetric in favor of the test treatment (Test) over the reference treatment (Control). These trials are designed to compare the relative efficacy of Test to Control by reference to a clinically important margin, M.
Main text
Non-inferiority trials allow for the conclusion of: (a) non-inferiority of Test to Control if Test is slightly worse than Control but by no more than M; and (b) superiority if Test is slightly better than Control even if it is by less than M. From Control’s perspective, (b) should lead to a conclusion of non-inferiority of Control to Test. The logical interpretation ought to be that, while Test is statistically better, it is not clinically superior to Control (since Control should be able to claim non-inferiority to Test). This article makes a distinction between statistical and clinical significance, providing for symmetry in the interpretation of results. Statistical superiority and clinical superiority are achieved, respectively, when the null and the non-inferiority margins are exceeded. We discuss a similar modification to placebo-controlled trials....."Of course, we'll all have to wait for the final reports but, in my humble opinion, it looks like MNKD WILL be able to claim Superiority. What do you all say? I don't think that means what you are concluding. The problem they are raising is that you can get divergent results depending if you are measuring statistical superiority or clinical superiority. Where margins are set in both dimensions it is possible for a result to be superior in one and non-inferior in the other which raises an ambiguity. What the paper says is that a drug should be superior by both statistical and clinical margins (" Statistical superiority and clinical superiority are achieved, respectively, when the null and the non-inferiority margins are exceeded".) Currently Afrezza fails to exceed the clinical margin and so could not be judged superior.
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