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Post by agedhippie on Jan 24, 2023 21:07:23 GMT -5
Don't feel alone with afrezza retention rates. The GLP1s are doing $11B and at least half the users stop using by the first year and nearly all by the second. The thing we know with the GLP1s is they are just masking the issue that the body is not making enough good insulin for the body's needs and the weight loss stops and then reverses when the PWD stops taking it. Now what they are seeing is the users end up gaining more weight as they have a new increased appetite. Its pretty crazy. ... Last year Trulicity had 13 million prescriptions filled, Ozempic had 16 million, both of these are almost doubling their TRx year on year. The total prescription dollars for those two alone last year was $42 million. Now if people are abandoning GLP-1 in droves, and there are around 35 million Type 2 diabetics, either retention is improving or next year there should be almost zero sales as they burn through the Type 2 population. Ok, that's a bit tongue in cheek since there is always a retention problem with any chronic disease (I must renew my statins at some point...) Last year the Afrezza TRx was 39.2k, and their NRx was 16.1k so the refills were 23.1k. So for every NRx Afrezza got 1.43 refills, and Trulicity (I picked Trulicity because it was a more mature product than Ozempic) got 1.6 refills. These numbers are all from Symphony/Bloomberg so they don't account for other channels, but what we are looking for here is ratios so that doesn't matter.
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Post by agedhippie on Jan 24, 2023 20:21:49 GMT -5
Dolly - this is a rather interesting post. Aged - f rom the FDA site "optimize drug dosing/therapeutic individualization in the absence of dedicated trials". This approach combines analytics with clinical data. Its also a pilot program so its brand new and has made up some new rules. The one thing afrezza has is some great clinical results and limited trial data so it just may be this pilot program came at just the right time. www.fda.gov/drugs/development-resources/model-informed-drug-development-paired-meeting-program... That is allowing a reduction in the data needed for phase 2 of the trial which is where dosing requirements are set. It doesn't negate phase 1, initial safety, nor phase 3, does the treatment work at scale. What it does do is allow a reduction of the phase 2 trial, what doses are appropriate, and allow optimization of the dosing regime in the phase 3 trial. Hence you see from the original paper abstract this: The FDA found the simulation framework to be helpful in providing insights into the question of interest and provides reasonable glycemic outcome predictions. At the conclusion of the MIDD paired meetings, FDA personnel from the Center for Drug Evaluation and Research review team accepted the simulation and requested additional, traditional clinical evidence to support the proposed label change.As to Nudge BG. The FDA requires the participant to partner with a software company that has a proven model. Nudge BG has an FDA approved model so you can feed in Afrezza's parameters and get a realistic result. Nudge BG itself is focused on a zero touch insulin model - a closed loop system where you don't need to say when you eat. Obviously Afrezza and zero touch are incompatible.
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Post by agedhippie on Jan 23, 2023 19:17:55 GMT -5
I am sure UTHR is also obligated to have a disaster recovery site. It was pointed out to me that Mike listed on his revenue slide "collaboration" as a revenue source. I think everyone fully expects the MNKD engineers to help UTHR set up the site. I see it nothing more than a disaster recovery site where they clear out the cobwebs a few times a year. However, MNKD is manufacturing at cost plus. Can Martine manufacture as cheap??? I don't know the plus up but I would guess 6%. If MNKD is doing a great job filling cartridges and Martine is selling the crap out of Tyvaso DPI, why would she ever risk screwing things up to save 6% if they can even produce as cheap as an experienced team who have years of DPI experience? Why on earth would UTHR spend the money to build a plant and then not use it. It's not like they can mothball it because then they would still have the ongoing costs of staff, certifications, supply chains, etc. It's far more likely that it would become the primary manufacturing site and UTHR could reclaim that cost plus element that they are currently leaving on the table as an additional benefit. As to support; MNKD are contractually obliged to provide that as part of the contract so that risk is minimal. This is before we get to UTHR being able to negotiate better prices from suppliers (they have the right to use their own suppliers in the contract).
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Post by agedhippie on Jan 23, 2023 18:29:46 GMT -5
...Also, why burden patients with the very cumbersome FDA approval/review processes when you have all the supporting evidence in hand? Afrezza-R could certainly be a candidate under this concept. agedhippie I'd like to get your insights, too. You mentioned in another thread some roadblocks for Afrezza-R. It reads like this could potentially become a credible consideration in the future of medicine. The process doesn't allow this process exclusively. They still require a traditional trial. What this does allow is the trial to be scoped in a way that would not have otherwise been possible (the data model can inform the trial design). As an example a model of the behavior of Azrezza would support (a) the fact that 1 Afrezza unit is not equal to 1 RAA unit and so allow higher doses, and (b) that there is faster clearance and so a lower probability of a hypo. This would justify a more aggressive dosing schedule than would be allowed under the old regime where all insulins were treated the same. That will help with both getting better results in trials, and with changing the dosing label. I should add, that's my reading of the FDA documentation and I am not either a doctor, nor a lawyer!
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Post by agedhippie on Jan 23, 2023 18:20:49 GMT -5
I believe sayhey24 is on the right track talking about cartridge fill rates. The dry powder is made in bulk batches, so manufacturing bulk material isn't the big problem, filling all those small cartridges is. So if you are thinking trade secret wise, keeping bulk powder manufacturing at Danbury makes sense and shipping the powder to finish fill lines somewhere else is fine. I think the original building had room for 12 lines(enough room for all USA AFrezza production) and only 2-3 were ever installed , and they have improved the fill rates over the years of the lines. Mannkind is contractually obliged to help UTHR set up manufacturing of any part of the product at UTHR's request. The contract also allows UTHR to sub-license the manufacture of any part of the product (it also allows the sub-licensee to sub-license and so on).
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Post by agedhippie on Jan 20, 2023 19:56:13 GMT -5
Why would the pump produce more insulin, when affrezza provided the adequate amount.. Have you ever known agedhippie to put anything forward regarding afrezza that wasn't a roadblock? Somebody has to answer the questions
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Post by agedhippie on Jan 20, 2023 19:55:13 GMT -5
Why would the pump produce more insulin, when affrezza provided the adequate amount.. Because the pump doesn't know about the Afrezza so it continues as if that never happened. Suppose you were at 300; the pump decides that you need 10u to get you back to the baseline and starts giving it to you, within about 5 minutes it will have given you most of the dose. At the same time you take Afrezza manually. Now you have a lot more insulin than you need and are almost certainly going to go low. You would have the same problem if you used a pen. If the pump was manual you could offset dose to allow for the Afrezza because you know about it, but the pump is automated...
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Post by agedhippie on Jan 20, 2023 16:40:03 GMT -5
There are two issues with the rescue inhaler idea.
The first is that there is no trial data to quantify the benefit - yes it will drop your level quickly, but in the grand scheme of things how much does it matter? Benefits not features - you have to be able to show the benefit. And no, saying but its obvious that it's better because it gets you to baseline faster doesn't does not quantify the benefit. Will people use it when they should, what is the reduction in complications, what does compliance look like, those sort of questions.
The second issue is that Type 1 diabetics are being pushed to use hybrid loop pumps these days. External insulin sources do not play nice with these since the pump algorithm assumes that the pump is the sole source of insulin so it's still going to try and correct the level, and suddenly you have an excess of insulin flying around... This isn't a problem with the old style pumps, or with pens, but those aren't were everyone is going.
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Post by agedhippie on Jan 19, 2023 19:43:06 GMT -5
What are the contractual obligations with the TS manufacturing process and patents? Did UTHR get all rights to manufacture when they signed the licensing deal?No. Actually yes It's section 5.2 in the contract. Mannkind agree to help them set up manufacturing: 5.2c) ...The Manufacturing Information will be of sufficient detail to enable a reasonably experienced manufacturer to manufacture, assemble, test, operate, and service the Initial Product.
And agree that UTHR can buy the raw materials directly from the manufacturer to produce the drug: 5.2d) The Parties agree that United Therapeutics has the right under Section 2.2 to source all raw materials for the manufacture of Product from the suppliers of its choice...(Section 2.2 allows UTHR to grant sub-licenses. That allows UTHR to have someone else manufacture all or part of the drug. It's also multi-tiered so they can grant sub-licenses below the sub-licensee) It's worth remembering that the expectation back when this started was that beyond the initial batch UTHR would manufacture the drug and Mannkind would get a royalty. In the interval UTHR sub-contracted manufacture to Mannkind on a longer basis which made sense for UTHR because it reduced their risk if something went wrong - they didn't want to be landed with a manufacturing plant for a poorly selling drug. This is why I think it is good that they are starting to exercise their options - they are now convinced it will be successful to the point where it makes sense to incur the cost of a manufacturing plant.
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Post by agedhippie on Jan 18, 2023 19:07:33 GMT -5
A portion of a new UTHR job opening; How you’ll contribute The Principal Process Engineer (DPI) will provide process engineering expertise for new facility projects, with a core focus on Tyvaso DPI related projects. Responsibilities include serving as the project point person from conceptual plan, detailed design, and construction. Additional responsibilities include equipment/process feasibility assessments, throughput analysis, process specification, and constructability assessments. ... My note; Several folks noticed even though Martine acknowledged Mike as the CEO of the Company that Mfgs. Tyvaso DPI at the JPM conference, she didn't say the company name. Why would she want any other name affiliated with a technology UTHR would soon exclusively own? JMHO Oddly I think it's good news for MNKD. Yes, the manufacturing revenue goes away, but there is no way UTHR would build their own manufacturing plant if DPI wasn't getting serious traction so there are the prospects for far greater royalties. I can't see them buying MNKD because in that case they would use or expand the existing facility.
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Post by agedhippie on Jan 17, 2023 11:00:03 GMT -5
The pediatric trials will move the needle. What child (or parent) would begin with less (or no injections) then opt for slower speed and needles? They will still need a daily basal injection with Afrezza, but it does avoid the four or so other injections. The competition isn't MDI, it's automated insulin delivery pumps. These are being very heavily pushed right now because something like the 780G is averaging out at a TIR of 74% in the real world. Endos really like that, and having kids on them reduces the need for the parents and kid to manage things which always helps. That TIR is better than Afrezza has achieved in trials so far.
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Post by agedhippie on Jan 14, 2023 15:36:54 GMT -5
Glp1 for diet. Maybe if you eliminate the nausea you also eliminate the weight loss? I don't think so. The GLP1 suppresses appetite with the feeling of being full. The nausea (diarrhea, constipation) are side effects. That's what I thought, that's even what Mannkind's scientists thought! However, reading the paper they published it seems you don't get the nausea, although they don't know why. They have data on a small sample set for the nausea, but they have nothing on weight loss because they weren't looking for that. The focus was on using GLP-1 to trigger insulin secretion.
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Post by agedhippie on Jan 14, 2023 12:28:53 GMT -5
I love the chatter here on this board as the back and forth is exciting reading where posters give their opinion on what course the CEO should take to resolve MannKind's dilemma. I'm not an expert on the issues, but I have noted one issue that baffles me, so I hope someone can give me a 25-word or less explanation. Don't confuse me with multisyllabic words. In the CEO's JP Morgan presentation, he showed a slide that indicated that Mannkind had secured 125,000 prescriptions with Afrezza. Since diabetes is a disease that requires patients to dose their prescripted medication constantly, this means the prescriptions must be refilled. Using a rudimentary application of math, these 125,000 prescriptions must be replenished constantly. Since the significant reporting agency issues weekly data for new prescriptions and refills, on the back of a napkin calculation, this would be 52 weeks in a year. Dividing the 125,000 by 52 weeks that would indicate that to refill the 125,000 prescriptions, the weekly average would be about 2,400 refills. Instead, it is reported that the average weekly refills are in the 400 range. Why aren't we seeing the other 2,000 being refilled? Liane is right, that's every prescription that has been written ever! The refill math is tricky. Based on my experience in the T1 world the usual pattern is each prescription being written for four quarterly refills, so an NRx followed by 3 refills. I suspect that for commercial insurances most will be handled like that because the PBMs pretty much force you down the quarterly refill path (typically with their mail order pharmacy). When you see an NRx there is a probability that it's really a refill (an existing person getting their next years perscription), or a real new patient. What a model for that would look like I am not sure, I would need to go away and think about that.
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Post by agedhippie on Jan 14, 2023 10:21:04 GMT -5
Glp1 for diet. Maybe if you eliminate the nausea you also eliminate the weight loss? Nobody knows, they weren't looking for weight loss in the trial. There is definitely potential there if the elimination of nausea can be shown in a larger trial. An explanation of why there is no nausea would be nice as well because currently they don't know ("The absence of an effect on gastric motility was a surprising finding.")
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Post by agedhippie on Dec 31, 2022 17:17:49 GMT -5
Matt could find and quote the section of the SEC manuals. He understood the material to the square root. As liane knows, there came a day myself, Lianne, Mango, and surprise Matt had a brief discussion about intubation. That was when I realized Matt was also a physician. A physician who intimately knew every booklet of the SEC. He was working for a hedge fund, shorting MNKD. Matt left with UTHR. Rbody knows they are shorteally a superior brain...... like that of only a number of brain surgeons. TBH the line "a physician who intimately knew every booklet of the SEC" describes any ex-physician like Matt who has been the CEO of a biotech (and I would bet there are quite a lot). The jump from knowing about SEC regulations to working for a hedge fund is quite a stretch. Lots of people have that knowledge; at the C-level minimally the CEO, CFO, and head of Legal, outside that most of the risk departments (where I come in), a large chunk of Legal, anyone in M&A, and that's far from complete. Over the course of a career you pick this stuff up - I could talk convincingly on seven or eight regulatory bodies in the US and UK (maybe some in Asia but that's very rusty now). I don't work in a hedge fund, nor have I ever worked for one beyond cleaning up (security breach) messes at a couple as a consultant a long time ago. I am going to put the second half of this post, how hedge funds actually work in and MNKD, in a more appropriate forum here - mnkd.proboards.com/post/245852/thread
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