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Post by agedhippie on Jun 27, 2024 18:52:18 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!
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Post by agedhippie on Jun 25, 2024 17:05:35 GMT -5
True Mango but the major problem is MINDSET. When Diabetics on insulin hear TAKE A HIGHER DOSE.....They freak out. Diabetics for 100+ years have been conditioned if they take too much insulin they will go into a diabetic coma so they AVOID the higher dose. The doctor (which is in the same boat) needs to be educated that taking a higher dose is fine. It's not a 1:1 comparison with SubQ. EDUCATION IS PRIORITY NOW for the salesforce. The question will be.....will doctors listen? Will they take notice of the data and CHANGE THEIR WAY OF TRAINING? It's on the doctors to explain that 1u of Afrezza is much weaker than 1u of RAA and so you need to take more. I don't see it being an obstacle if they understand why their endo is telling them to take more. The bigger question is if the salesforce is allowed to talk to doctors about this since they cannot go off-label in selling and the label sets the dose. This is why the label still matters. The KOLs like the panel are all endos in big hospital systems, the question is what it looks like when you get away from those hospitals? The second question is how much those other prescribers matter to sales.
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Post by agedhippie on Jun 25, 2024 7:19:23 GMT -5
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Post by agedhippie on Jun 25, 2024 7:15:14 GMT -5
I tried to find the exact ratio but failed miserably. The best I could do was an earlier reference is a paper trying to establish that equivalence. They dosed 25, 50, and 100 units to try and establish which had the equivalent effect of 10u of RAA. That feels like the pre-conversion units since I would expect to see 4, 8, and12 units. In theory 10u of RAA would be bracketed by 8u and 12u of Afrezza. The reason why Afrezza takes more insulin than RAA is because more of it gets lost enroute to the bloodstream (prcgorman2 outlined several of the issues). Lungs are an effective, but not terribly efficient delivery mechanism. The trial estimated the efficiency at 23% of RAA. Getting the ratio of the conversion is important assuming it was 4x should it really be 10x? At this point someone usually asks about all that extra insulin API, and the answer is that it is utterly irrelevant - what matters is the insulin that hits the bloodstream and not what goes astray enroute. Insulin API is free to a first approximation. Reference for the paper: www.ncbi.nlm.nih.gov/pmc/articles/PMC4634344/
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Post by agedhippie on Jun 24, 2024 18:17:55 GMT -5
I'm pretty sure you are incorrect about that. Units of insulin represent equivalent monomeric insulin molecules. I have no degree in anything but work. Yet the consistent under dosing suggest to me somethings far less than equal. Personally you put this in my hands given everything I have read to date. I would multiply by six then half it for the sake of quick in and out affect for starters. The reason is that inhaled insulin is not particularly efficient so 1u of Afrezza is actually a lot more raw insulin than 1u of RAA. Turns out MNKD underestimated the amount of insulin needed to reach equivalence hence the need for more apparent units.
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Post by agedhippie on Jun 23, 2024 13:56:25 GMT -5
... The last few I feel Doctors know it works but are still hesitant. Even this study pointed out patients needed 2.5-3 ratio for Afrezza over rapid acting injectable. Not the 2-1 ratio, I think has been the mainstay. ... "The panel of INHALE 3 investigators suggested that poor candidates might include those patients with a fear of hypoglycemia that keeps them from dosing at bedtime, or who have a lot of auto boluses given by their automated infusion pump suggesting that they're not proactive about management." www.medpagetoday.com/meetingcoverage/ada/110781The official to actual ratio for units needs to be fixed, but I am not sure that is possible at this time. If 1u of Afrezza was normalized to 1u of RAA the apparent cost of Afrezza would look terrible (2.5x the current price). The link to medpagetoday is good. It is a report of the symposium and not just a regurgitation of the ADA release. I dislike the line about not being pro-active in their management as it lack context for why they are relying on the AID pump to do the work - a topic on which I have ranted extensively.
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Post by agedhippie on Jun 23, 2024 9:20:33 GMT -5
So Aged, what do you think? It seems with the CGM Inhale 3 did better than the one testing site during the 171 when the FDA accused the good doctor of cheating. ... I think you have told us T1s don't like to switch a routine which was working. More than 50% of subjects at the end of the study expressed an interest in continuing to use Afrezza® Now thats pretty shocking. ... Ten years down the line I would definitely expect we could do better that the 171 trial. As for the rest; show me the data and not a headline. You have a trial population who are not conservative about their routine or they wouldn't be in a clinical trial. That 50% number is not surprising at the end of the trial, but what it doesn't do is breakdown the strength of feeling or the role they see for Afrezza in their future. Is it - yes we will definitely swap, or possibly we will keep some around as a rescue inhaler? Again, data please.
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Post by agedhippie on Jun 23, 2024 9:05:48 GMT -5
I liked the way the ADA PR was written better than Mannkinds either way the results are awesome and Im extremely hopeful the 13 week extension is only going to get better. Lets Go! I really want to see the data from this trial. I suspect that Dr Hirsch will publish his paper in the Diabetes Care so I am eagerly waiting for that.
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Post by agedhippie on Jun 23, 2024 9:02:44 GMT -5
Do these results now get presented to The FDA for possible label changes ….. Black box , possible superiority.. 🤞 I think a label change is possible down the road as a result of this trial. There was a comment by Dr Hirsch, " The bottom line is we need to understand appropriate dosing for both the inhaled and the basal insulin." You can see why when the bolus to basal ratio is 70:30 rather than 50:50 as those numbers imply that Afrezza is half the strength it claims. Fixing that will stop less experienced endos from under-dosing and wondering why Afrezza doesn't work. So; - I think there will be label changes, but not yet as I suspect they will need more specific trials for that. - Black box will not change as that has nothing to do with Afrezza's effectiveness and is a DPI matter. - Interestingly a lot of the secondary outcomes were collected to show superiority at the 17 week mark but no claims were made over that. For me the main thing was a large number of endos hearing a panel of KOLs say they liked Afrezza and it was useful. This should help dispel some of the FUD that has accumulated over the years. There was a particularly interesting comment in the ADA symposium PR; Moving forward, Dr. Blevins said it will be important to further define guidelines and best practices for the use of inhaled insulin. However, it will ultimately be up to patients and their providers to determine whether the therapy is right for them.That could lead to a consensus on how to use inhaled insulin and potentially inclusion in the SoC. Not soon, but in the future.
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Post by agedhippie on Jun 23, 2024 8:16:31 GMT -5
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Post by agedhippie on Jun 21, 2024 8:57:43 GMT -5
Superiority and safety is what Im anticipating from this weekends announcements. Non inferiority is the least I could expect. And from the moves im seeing MC making my anticipation may be warranted. If there is any truth to an insulin pen shortage afrezza my get a helping hand into an accelerated insurance coverage from our competition stranger things have been known to occur over the years here. There is an insulin pen shortage. I got swapped to Novolog because of the Humalog shortage and the PBM bumped the cost of co-pays for Humalog to drive the point home.
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Post by agedhippie on Jun 21, 2024 8:52:49 GMT -5
Maybe my understanding is different than what some have expressed here. Considering that Afrezza is the odd man out, I think that even non inferiority is a good outcome. I try to keep in mind that PWD won't be able to get a prescription for inhaled insulin until they've tried 1 or 2 RRA first. Being able to show that Afrezza is at the very least the same would/should equalize access to the inhaled option without having to jump through hoops. Of course superiority would be ideal, don't get me wrong, but there is a lot of good news even in non inferiority Afrezza is already rated as non-inferior to RAA, that is part of the insurance problem. Since it is non-inferior today insurers use the equivalence rules and pick an RAA for their meal time insulin. That's just how the system works - Afrezza is far more expensive and insurers want to make a profit. For me the important thing here is less the results and far move the visibility that Afrezza will get. The people they have presenting matter to other endos. That is what will get endos to think maybe they could have the prior authorization fight with the insurer to try Afrezza. The key is to get endos to try it, the rest will follow.
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Post by agedhippie on May 31, 2024 16:09:00 GMT -5
Anyone else wondering why there's such a delay from the FDA with Yutrepia? It's because LQDA didn't split PAH and PH-ILD. That means approval is hung up on whether UTHR get an injunction for PH-ILD or not. The hearing for the injunction was last week so there may be a ruling this week. My feeling is that UTHR will not get the injunction, but if they do UTHR will have to file a bond for damages (probably $200M at a guess) to be paid to LQDA if the "327 patent is invalidated. There is a separate case with UTHR suing the FDA but I don't think that goes anywhere. The judge told them that they cannot sue on a hypothetical so they will have to wait for the FDA to approve and then sue the FDA. Well that was a couple of weeks later than I predicted! The judgement is finally in and UTHR lost again - there will be no injunction in the '327 patent case so LQDA can launch for PH-ILD (PAH was not in scope for this lawsuit) when the FDA approves Yutrepia. How long the FDA take is anyone guess, but I suspect after this it may be reasonably soon. There were a couple of interesting comments. The judge found that in the PH-ILD market Yutrepia was unlikely to impact Tyvaso sales since by 2030 UTHR only expected to serve half the available market. The other was UTHR's claim that Yutrepia's entry into the market would likely force UTHR to reduce their price by 20% to 30%.
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Post by agedhippie on May 31, 2024 15:26:44 GMT -5
... The dosing is wrong and calling them 4u 8u and 12u was a huge marketing mistake. They should be small, medium and large. ... The problem for insurers is not the black box. Its the SoC. It is not in the SoC. Its not in the SoC because we did not do proper trials with proper dosing. Why have we not done that in 8 years for the T2s? Instead we buy V-Go. ... Calling doses small, medium, and large, would have doomed Afrezza on the spot. In the aftermath of the Exubera fiasco where they hadn't used standard insulin units it was simply untenable. It would also have killed the Type 1 market, which turned out to be the only place it sold, stone dead because endos want units. Afrezza is in the SoC, search for inhaled insulin.
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Post by agedhippie on May 29, 2024 21:54:44 GMT -5
The two companies also agreed that Pulmatrix will transfer its Bedford, Mass. R&D facility to MannKind, along with all leasehold improvements, laboratory equipment and other related personal property used in the laboratory in non-cash transaction. Were they going bankrupt? Pulmatrix Inc Follow NASDAQ: PULM Market cap of 7m. More like trying to avoid going bankrupt. PULM have offloaded their lease and operations costs to lower their burn rate while they do their phase 2 trial, and MNKD has got an R&D facility that they can consolidate into. I would be shocked if either side ever exercised their rights to the other sides technology - that's fluff.
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