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Post by sportsrancho on Jun 14, 2023 8:22:41 GMT -5
It's never too late to revisit a partnership. Would love to know MC's current perspective forgoing the disappointing history. It's a complicated thing with the FDA because we prescribe off label. ( But that’s how we get our results.) |
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Post by prcgorman2 on Jun 14, 2023 8:27:54 GMT -5
That's my sense too. I've assumed the reason for a general lack of interest was not because of a lack of willingness to consider it as much as being "complicated". Bridge too far as it were. VDEX is a great arm's length partner and I hope Bill is richly rewarded for putting his money where his mouth is. That's the proof of conviction and I respect it.
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Post by cretin11 on Jun 14, 2023 10:31:01 GMT -5
It's never too late to revisit a partnership. Would love to know MC's current perspective forgoing the disappointing history. Totally agree. One can learn from mistakes, and it is my sincere hope that MC is capable of that (on numerous fronts). Put ego aside and make decisions that are best for the company moving forward, that is a reasonable ask by us. Better late than never (at least for those of us still in this investment)! |
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Post by prcgorman2 on Jun 14, 2023 10:34:26 GMT -5
Is there anything more to discuss about the upcoming ADA conference?
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Post by agedhippie on Jun 14, 2023 10:58:48 GMT -5
That's my sense too. I've assumed the reason for a general lack of interest was not because of a lack of willingness to consider it as much as being "complicated". Bridge too far as it were. VDEX is a great arm's length partner and I hope Bill is richly rewarded for putting his money where his mouth is. That's the proof of conviction and I respect it. ^This. It's a problem with any jump in treatment/technology/change - you have to educate the market and that is a heavy lift because you are changing perceptions. Bill saw the potential, set up VDEX, and was prepared to devise a protocol that didn't strictly tie to the label. The problem is that the rest don't move as fast. My old endo prescribed metformin off-label for Type 1 patients for years despite the FDA and ADA being fairly solidly against that idea - now it's mainstream. Educating the market in this case is about trial data. Papers are written about the results and gradually the idea becomes talked about and after a couple of years the SoC starts to change. |
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Post by phdedieu12 on Jun 14, 2023 12:36:00 GMT -5
It's time to realize that MNKD is no longer (just) Afrezza. It's time to stop worrying about it, it will only be one of the many revenue streams. MNKD is a delivery platform, it will have many molecules and funds will be deployed where the results are more evident. It is Tyvaso, it will be Clofazomine and many more. Some resources will go to Afrezza, hopefully the upcoming trials will prove positive and provide a nice uptick, but this is no longer a one trick pony and MC is now looking at a very different company, not just one asset
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Post by akemp3000 on Jun 14, 2023 12:58:45 GMT -5
Yes. Al Mann created this company to be a developmental company for multiple applications based on the Technosphere platform. In hindsight, he made a mistake of picking diabetes, the highest mountain in the world to climb as the first battle. When Sanofi left, the company was forced to go it alone and quickly become a manufacturing company which was not the intent. One of the first things Michael Castagna did as CEO was to overhaul the business plan and return the company back to a developmental company with the primary focus being the pipeline, not Afrezza. It was an excellent decision that likely saved the company.
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Post by carefulinvestor on Jun 14, 2023 13:29:54 GMT -5
Just curious, why would diabetes be the "highest mountain"? - - due to BP cartel organized opposition? Otherwise, based on need and market size, it seems Al was right on target. Thoughts please (happy face).
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Post by sayhey24 on Jun 14, 2023 14:15:58 GMT -5
Just curious, why would diabetes be the "highest mountain"? - - due to BP cartel organized opposition? Otherwise, based on need and market size, it seems Al was right on target. Thoughts please (happy face). It's all about the BP Cartel but if Al had not gotten sick he would have strong armed the ADA to do the right thing. Even in the face of a corrupt FDA review he was able to strong arm the FDA to approve for both T1 and T2. Few expected T1 approval. Al envisioned MNKD as a manufacturing company leveraging the technosphere platform. He was working on several other drugs including glp-1 but money was running out so afrezza was the focus. Was Al correct in going after the diabetes market. IMO absolutely. He believed he had the greatest advance in diabetes care in 100 years and I agree with him. He thought afrezza was going to be the greatest selling drug of all time. I think if MNKD could put a glp-1 on TS which did not have the same nausea issues current analogs have that would be the greatest because of the diet market but if not afrezza should be. So whats the issue? Mike never knew how to sell it and that includes what needed to be done to sell it. Al never did the big long term trials properly dosing afrezza. His plan was to get it approved and then sign a marketing partner who would do all those trials which Sanofi was suppose to do. When Mike showed up he knew very little about the diabetes industry including the players and technology like CGMs and remote monitoring. He seemed to think he would run a flying hamburger commercial on TV and put afrezza in the sales reps bags and it would magically sell. It took him 5 years to even seem to figure out the afrezza dosing on the label was wrong. I could go on and on. The issue was not that Al went after the diabetes market. He would have gotten it done. The issue is MNKD has never had a CEO who could fill the shoes left empty by Al in the diabetes market. Will Mike get there? I hope so. The kids trial will help. The India trial if the results are as good as Mike mentioned will help. The afrezza/glp-1 trial is huge but has not even started yet. Afrezza has to show significant post prandial control and additional A1c gains when added to Ozempic and Mounjaro. Medicare 2024 with no pre auths will be big - assuming Mike got this done. If so he can start putting plans in place for how both Dexcom and Abbott can leverage afrezza to sell CGMS in the Medicare market and have those meetings with Robert Ford and Kevin Sayer at ADA2023 next week - hope springs eternal. |
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Post by agedhippie on Jun 14, 2023 14:23:24 GMT -5
Just curious, why would diabetes be the "highest mountain"? - - due to BP cartel organized opposition? Otherwise, based on need and market size, it seems Al was right on target. Thoughts please (happy face). In my opinion? You are changing the delivery paradigm, the behavior of the treatment, and the dosing all in one go. That's a huge ask for a life supporting drug without a ton of compelling data and papers. I feel that Al Mann, being at heart an engineer rather than an endo, underestimated that. With Tyvaso DPI you are going from an inhaled (nebulized) to an inhaled (DPI) drug and that is a far more comfortable change. I think choosing insulin was a bridge to far (to echo an earlier poster), but if you could prove TS with insulin by getting a big win then you would have a queue at the door. |
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Post by prcgorman2 on Jun 14, 2023 16:04:46 GMT -5
Just curious, why would diabetes be the "highest mountain"? - - due to BP cartel organized opposition? Otherwise, based on need and market size, it seems Al was right on target. Thoughts please (happy face). In my opinion? You are changing the delivery paradigm, the behavior of the treatment, and the dosing all in one go. That's a huge ask for a life supporting drug without a ton of compelling data and papers. I feel that Al Mann, being at heart an engineer rather than an endo, underestimated that. With Tyvaso DPI you are going from an inhaled (nebulized) to an inhaled (DPI) drug and that is a far more comfortable change. I think choosing insulin was a bridge to far (to echo an earlier poster), but if you could prove TS with insulin by getting a big win then you would have a queue at the door. Thank you agedhippie. Can you elaborate the phrase in bold please? (Not setting a trap, but didn't understand.) |
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Post by agedhippie on Jun 14, 2023 17:06:59 GMT -5
In my opinion? You are changing the delivery paradigm, the behavior of the treatment, and the dosing all in one go. That's a huge ask for a life supporting drug without a ton of compelling data and papers. I feel that Al Mann, being at heart an engineer rather than an endo, underestimated that. With Tyvaso DPI you are going from an inhaled (nebulized) to an inhaled (DPI) drug and that is a far more comfortable change. I think choosing insulin was a bridge to far (to echo an earlier poster), but if you could prove TS with insulin by getting a big win then you would have a queue at the door. Thank you agedhippie. Can you elaborate the phrase in bold please? (Not stting a trap, but didn't understand.) Fundamentally it's echoing what was said earlier by others. This is my supposition based on why I would have taken this decision; various pharmas were developing inhaled insulins and letting them drive the changes needed made sense (never be the one to educate the market), coupled with insulin being a critical drug (the patient dies if it doesn't work) made this a high profile choice. If Technosphere could deliver this the expectation is that it could deliver any small molecule. So what went wrong. In a word, Exubera. Commercially it was an utter failure because there was no compelling case. Non-diabetics fixate on needles and build a whole mythology around injecting, this is at complete odds with reality - largely Tupe 1s don't care, it doesn't hurt, and we use insulin when we want and if someone objects that's their problem. (This is my experience with other Type 1s.) The selling point of inhaled insulin, no needles, is fundamentally flawed and we need to move beyond that to outcomes. What is the problem now? The market place has completely changed from when Afrezza was launched. The competition in the Type 1 world is no longer MDI and the occasional CGM (I used to pay for my own they were so hard to get on insurance), it's AID pumps that watch your levels and autocorrect every 5 minutes giving TIR in the mid 70 and upwards range with minimal work. In the Type 2 world the problem is GLP-1, has become GLP-1/GIP combinations, and will probably evolve to GLP-1/GIP/Glucagon combinations. In other words insulin is no longer an automatic next step with these drugs addressing more than just glucose levels, but also lipid and cardiac issues as well (weight loss is not great with the doses diabetics use). Well that's bleak. So I think Afrezza should be abandoned? No. People like VDEX have proven it can work if used correctly, Dr Edelman and Dr Hirsch have shown how it can be used as a supplement to AID pumps, and the absorption is still not to be underestimated. There is a definite market for Afrezza and I would be loathed to see it scrapped (contrary to what people think) as I think it has roles, but it's never going to replace RAA because the drugs and technology of today have moved on from where they were fifteen years ago. There you go, a far longer answer than I intended so congratulations if you made it to the end  |
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Post by lennymnkd on Jun 14, 2023 18:50:45 GMT -5
Aged what would you like to see statistically right across the board for Afrezza to be commercially effective
The way you see it must be done .. to make Afrezza a success !
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Post by agedhippie on Jun 14, 2023 22:44:41 GMT -5
Aged what would you like to see statistically right across the board for Afrezza to be commercially effective The way you see it must be done .. to make Afrezza a success ! It's a good question and obviously this is just my opinion. I reckon a TIR of an absolute minimum of 70%, ideally about 75%, over a three month period. Minimal second doses 4 or 5 doses a day is viable, 7 doses isn't, basically not twice every meal. An A1c on the lower side RAA, it doesn't need to be superior just better. The lower hypos is good. Sort out the RAA to Afrezza unit mapping - the double it and round down looks good. They are going to need a higher capacity cartridge because the 12u is not big enough, you need a single hit rather then two or three cartridges for a dose. You need solid trial data to support the claims which means properly sized arms of around 100 people each for a minimum of three months. The data is critical because that drives papers in Diabetes Care which is the chief source of information for endos, probably Lancet or NEJM for the general medical population. Those papers change minds. |
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Post by prcgorman2 on Jun 15, 2023 6:39:36 GMT -5
Excellent points. Can’t just outperform RAA, and KISS principle (Keep It Simple Silly) applies. Make it easy to control your diabetes. CGMs help of course and those are just going to continue to get better, cheaper, smaller, easier. You and others convinced me long ago that at a minimum Afrezza can be a great tool in the toolkit to kill spikes if nothing else. I think a much smaller dose than usual of RAA in combination with Afrezza for mealtime spike might be very effective management approach with less hassle. Mileage will vary.
The mix of GLP, etc., makes this a more complicated picture. Testing with these is also important if for no other reason than to help prescribers and patients who will want some idea how to benefit from Afrezza in the toolkit.
What do you think of the direction that Mike Castagna and Sayhey24 have mentioned with an extra-slow basal (e.g., 1 shot per week) in combination with Afrezza (which is a sort of variation on what I said about low-dose RAA + Afrezza)?
And thank you very much for being generous with your information and for the great debates with Sayhey. You guys are the best.
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