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Post by sayhey24 on Aug 11, 2023 14:57:54 GMT -5
Why do you think you failed finding AGPs for GLP1 users? I sound like a broken record on this. Mike needs to do the study and then you will be able to find them. He said a few calls back they were going to start the pilot. One arm is suppose to be adding afrezza to the GLP1. The thing is, it doesn't really matter short term which one wins. Long term the PWDs stop using the GLP1s. My point is Mike needs to be positioned to fill that gap. If he can show adding afrezza to the Medicare GLP1 users they can also get an almost free CGM. He also needs to do the Victoza DPI pilot and prove this will never work for the diet market. But then again, maybe it will. On Monday he did say they have bandwidth to run some pilot studies. Because an APG is meaningless in a clinical trial - they are individually tailored. Notice that there are no Afrezza APGs either? You keep saying that diabetics quit GLP-1 in the long term, but you are failing to account for that being by design (protocol). Once their HbA1c is in range they can stop and go back on it a year or two later if necessary - that a cycle that is being used in Europe and probably in the US. The idea that on top of everything else you have to worry about a CGM is not a great sales pitch. People want a magic bullet which is why Ozempic is such a huge seller for weight loss and diabetes. Mike is not going to seriously follow up on GLP-1 because the science says it is very unlikely that you get a different result from injected GLP-1 analogs at which point a daily Victoza loses to a weekly Ozempic. He knows that so other than PR he isn't going down that path. Wow, you have now brought up something I never considered. You said - "Once their HbA1c is in range they can stop and go back on it a year or two later if necessary" I was not aware GLP1s were curing T2 diabetes. I was aware Al Mann had some pilot studies showing afrezza reversed the disease in some cases but I think GLP1s doing this is breaking news. When I googled on it I did find this "The study authors hypothesized that because of its mechanism of action, LIRA “could address the multiple pathogeneses of T2DM,” and therefore, “should bring complete remission of T2DM in newly diagnosed patients.” AACE 2017 Meeting; Drugs Context. 2015; 4: 212283. Published online 2015 Jul 9. doi: 10.7573/dic.212283 Now - this was published 8 years ago. if you have a link showing GLP1s reversing diabetes could you please post it. I have no idea what an APG is but I think you mean AGP. Why they are meaningless in a clinical trial is a head-scratcher to me. In fact collecting CGM data is becoming the norm. I am a simple guy and what Bill from VDex publishes I find valuable. For example his normal BG example static1.squarespace.com/static/5a37ff648fd4d234be3cea06/t/5d8d07778c19b57ec64e5202/1569523580485/vdex-whitepaper-092619.pdfYou could be correct and Mike is not going to seriously follow up on GLP-1 TS because the science says it is very unlikely that you get a different result from injected GLP-1 analogs. If it gives us the same results I say " TOUCHDOWN". That would be huge, IMO. Mike's thinking when looking at Victoza DPI was for diabetes. I want it for the diet market. He was not thinking diet. In the end he may say he doesn't want to be in the diet market. He may say GLP1s are going to get hit with all kinds of lawsuits and he may be right. Mike's friend at Pfizer thinks if they have an "oral" solution the diet market is a $90B market. Is "inhaled" good enough to make that market or does it have to be a pill? I say "inhaled" is a big step from injected. Does it make the $90B market? I am good if its only $50B. Inhaled will take the "Shaming" away if in fact the shaming is mostly associated with the injection. |
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Post by agedhippie on Aug 11, 2023 18:26:16 GMT -5
Wow, you have now brought up something I never considered. You said - "Once their HbA1c is in range they can stop and go back on it a year or two later if necessary" I was not aware GLP1s were curing T2 diabetes. I was aware Al Mann had some pilot studies showing afrezza reversed the disease in some cases but I think GLP1s doing this is breaking news. When I googled on it I did find this "The study authors hypothesized that because of its mechanism of action, LIRA “could address the multiple pathogeneses of T2DM,” and therefore, “should bring complete remission of T2DM in newly diagnosed patients.” AACE 2017 Meeting; Drugs Context. 2015; 4: 212283. Published online 2015 Jul 9. doi: 10.7573/dic.212283 Now - this was published 8 years ago. if you have a link showing GLP1s reversing diabetes could you please post it. ... Let's be clear on this. it has never been shown that Type 2 diabetes can be cured, but it can be put into remission. Weight loss reduces insulin resistance and sufficient weight loss can allow people's own insulin to be sufficient for their needs and that is the entire point of the Newcastle protocol that the UK NHS uses. The link to GLP-1 is obvious in this model, it facilitates that weight loss. Again though; Type 2 diabetes can be put into remission but cannot be cured. Reversing is an imprecise term since it can either refer to remission, or cure which are not the same. |
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Post by mayday on Aug 11, 2023 18:54:06 GMT -5
Good discussion lol
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Post by sayhey24 on Aug 12, 2023 8:15:39 GMT -5
Wow, you have now brought up something I never considered. You said - "Once their HbA1c is in range they can stop and go back on it a year or two later if necessary" I was not aware GLP1s were curing T2 diabetes. I was aware Al Mann had some pilot studies showing afrezza reversed the disease in some cases but I think GLP1s doing this is breaking news. When I googled on it I did find this "The study authors hypothesized that because of its mechanism of action, LIRA “could address the multiple pathogeneses of T2DM,” and therefore, “should bring complete remission of T2DM in newly diagnosed patients.” AACE 2017 Meeting; Drugs Context. 2015; 4: 212283. Published online 2015 Jul 9. doi: 10.7573/dic.212283 Now - this was published 8 years ago. if you have a link showing GLP1s reversing diabetes could you please post it. ... Let's be clear on this. it has never been shown that Type 2 diabetes can be cured, but it can be put into remission. Weight loss reduces insulin resistance and sufficient weight loss can allow people's own insulin to be sufficient for their needs and that is the entire point of the Newcastle protocol that the UK NHS uses. The link to GLP-1 is obvious in this model, it facilitates that weight loss. Again though; Type 2 diabetes can be put into remission but cannot be cured. Reversing is an imprecise term since it can either refer to remission, or cure which are not the same. OK - just to be clear you are saying GLP1s are designed to only be used for a short period of time. And then what? The PWD gains back the weight and loses BG control and in a year or two goes back on the GLP1? I am not sure that approach is outlined in the T2 SoC. I also bet as soon as they stop using and their food flows normally through the digestive system we will see post meal spiking and that 92% TIR will be in the rear view mirror. How about Mike does the afrezza/GLP1 study and demonstrates the benefits of adding and then backstopping the GLP1 with afrezza. He said he was going to do the study. On Monday he said they now had the bandwidth to do a pilot so lets hope he starts it. If GLP1s can be a gateway drug for afrezza, I am good with that. What I am really interested in is when you said it would be very unlikely that you get a different result from injected GLP-1 analogs than my proposed Victoza DPI. If you are correct, that IMO would be HUGE. We get the same weight loss action with Victoza DPI and no injection which then may mean no social shaming and we unlock what Mike's friend Albert Bourla said was a $90B market. I would even be OK doing a deal with Albert showing him the results you predict. I wonder if Mike has called his friend yet? I hope so. |
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Post by agedhippie on Aug 12, 2023 9:23:37 GMT -5
OK - just to be clear you are saying GLP1s are designed to only be used for a short period of time. And then what? The PWD gains back the weight and loses BG control and in a year or two goes back on the GLP1? I am not sure that approach is outlined in the T2 SoC. I also bet as soon as they stop using and their food flows normally through the digestive system we will see post meal spiking and that 92% TIR will be in the rear view mirror. I don't consider two years a short period of time although all things are relative. The UK NHS has it's own T2 SoC, as do most countries, so they are likely to differ from the US. You would lose that bet since if that was happening the patient would not be in remission - remission means no symptoms. What is the benefit of combining Afrezza and GLP-1 over just taking either Afrezza or GLP-1? That is what the trial would need to quantify - how the treatment translates into an actual reduction in complications (not it reduces spikes, but how many few CVD cases are there or how much is progression slowed for example.) Is Bourla really a friend or did they just happen to work in the same company of several thousand people at one point? (Genuinely asking as I don't know what the relationship is) If you get the same side effects for inhaled vs. injected GLP-1 analogs (as I expect) then what is the benefit to Pfizer is dumping their pill that they have spent millions on developing and have just about ready to go and delaying entering the GLP-1 market for a couple of years while an inhaled version is developed and trialed? |
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Post by prcgorman2 on Aug 12, 2023 10:49:06 GMT -5
Excellent. I need some popcorn.
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Post by sayhey24 on Aug 13, 2023 7:49:16 GMT -5
OK - just to be clear you are saying GLP1s are designed to only be used for a short period of time. And then what? The PWD gains back the weight and loses BG control and in a year or two goes back on the GLP1? I am not sure that approach is outlined in the T2 SoC. I also bet as soon as they stop using and their food flows normally through the digestive system we will see post meal spiking and that 92% TIR will be in the rear view mirror. I don't consider two years a short period of time although all things are relative. The UK NHS has it's own T2 SoC, as do most countries, so they are likely to differ from the US. You would lose that bet since if that was happening the patient would not be in remission - remission means no symptoms. What is the benefit of combining Afrezza and GLP-1 over just taking either Afrezza or GLP-1? That is what the trial would need to quantify - how the treatment translates into an actual reduction in complications (not it reduces spikes, but how many few CVD cases are there or how much is progression slowed for example.) Is Bourla really a friend or did they just happen to work in the same company of several thousand people at one point? (Genuinely asking as I don't know what the relationship is) If you get the same side effects for inhaled vs. injected GLP-1 analogs (as I expect) then what is the benefit to Pfizer is dumping their pill that they have spent millions on developing and have just about ready to go and delaying entering the GLP-1 market for a couple of years while an inhaled version is developed and trialed? This is business. Mike is not asking for a date. Whats the difference whether you know the guy to say hello in the hallway or you go out for drinks together. Bourla has an opportunity and an issue. His drop out rate says it all. Maybe Mike has a solution. Lets run a pilot and see. If you have the guys number and you say you know him, give him a call. Whats worst case, his admin blocks Mike. So what, keep trying. When you finally talk with him, maybe he laughs at you but then again maybe not. What I do know is Peter Richardson had some good success with native GLP1 and Martine is having great success with Tyvaso DPI. I think you can put an elevator pitch together around that. As far as the US vs the UK, maybe Mike can just focus on the US Medicare market for now. If he can get 10% of the T2s on Medicare that would be a huge start and he can then build from there. If he can sell some CGMs along with it, even better. Last year he pretty much wrote off Medicare and his solution was V-Go for the T2s.. Last Monday he now says its his growth market for afrezza. Lets see what the India A1c numbers really are and hopefully he can craft a plan around them. In the mean time he needs to start the GLP1/afrezza pilot for the T2s. |
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Post by agedhippie on Aug 13, 2023 9:26:57 GMT -5
... If you have the guys number and you say you know him, give him a call. Whats worst case, his admin blocks Mike. So what, keep trying. When you finally talk with him, maybe he laughs at you but then again maybe not. What I do know is Peter Richardson had some good success with native GLP1 and Martine is having great success with Tyvaso DPI. I think you can put an elevator pitch together around that. As far as the US vs the UK, maybe Mike can just focus on the US Medicare market for now. If he can get 10% of the T2s on Medicare that would be a huge start and he can then build from there. ... So Mike is trying to cold call the CEO of one of the largest pharmas in the world who doesn't know him from a hole in the wall as far as we can tell. I absolutely guarantee he gets blocked and I doubt he even reaches the admin. There will be hundreds of people a day trying to call him and those calls get (politely) dumped. You cannot have a CEO at that level getting off schedule. Right now 28% of Afrezza sales are going to Medicare which equates to the percentage other RAA pharmas see. I expect it to go up a few points from here since Afrezza doesn't currently have a pediatrics market and so it is weighted to the older end, but that sounds like a ceiling. He is not getting 10% of T2 on Medicare, the SoC is in the way of that. |
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Post by sayhey24 on Aug 14, 2023 8:30:47 GMT -5
... If you have the guys number and you say you know him, give him a call. Whats worst case, his admin blocks Mike. So what, keep trying. When you finally talk with him, maybe he laughs at you but then again maybe not. What I do know is Peter Richardson had some good success with native GLP1 and Martine is having great success with Tyvaso DPI. I think you can put an elevator pitch together around that. As far as the US vs the UK, maybe Mike can just focus on the US Medicare market for now. If he can get 10% of the T2s on Medicare that would be a huge start and he can then build from there. ... So Mike is trying to cold call the CEO of one of the largest pharmas in the world who doesn't know him from a hole in the wall as far as we can tell. I absolutely guarantee he gets blocked and I doubt he even reaches the admin. There will be hundreds of people a day trying to call him and those calls get (politely) dumped. You cannot have a CEO at that level getting off schedule. Right now 28% of Afrezza sales are going to Medicare which equates to the percentage other RAA pharmas see. I expect it to go up a few points from here since Afrezza doesn't currently have a pediatrics market and so it is weighted to the older end, but that sounds like a ceiling. He is not getting 10% of T2 on Medicare, the SoC is in the way of that. Its come to the point where its insulting when afrezza is compared to an RAA. Its nothing like an RAA. Its so much more and its real strength is in the T2 market. Mike has already told us the preliminary numbers from India are in the 1.5 - 2% A1c reduction range. If true he should have some ammo for the T2 SoC and should be able to enlist the CGM vendors for support. I can't do Mike's job for him. Step 1 is getting the pre auths for 2024 removed. Step 2 is leveraging the India results to justify T2 SoC changes. Step 3 is doing the glp1/afrezza study to provide a transition path. OK - now you say Mike can't make a phone call. Al has an issue. Mike may have a solution. Problem solved - I dropped Al a note so he is expecting Mike's call. Mike needs to stop wasting time and see if Victoza DPI works. Maybe Al has an interest in putting his molecules on TA, maybe not. If Victoza DPI works as you predict, "Touchdown". |
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Post by akemp3000 on Aug 14, 2023 9:06:47 GMT -5
This great 21-page thread debate of GLP-1 here is highly educational and appreciated. That said, IMO, it's also very likely this same debate has also been discussed extensively inside Mannkind management and probably to a much higher scientific degree among experts. Too bad we can't hear what they know. Wish they would chime in and resolve some of the issues being discussed or at least explain why they're not pursuing this aggressively. I hope this debate continues. Just offering a random thought.
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Post by uvula on Aug 14, 2023 9:20:35 GMT -5
One thing I don't understand about this thread and similar threads.
I'm just making up numbers to make a point.
If a one time spend of $30M for clinical studies will lead to making $2B per year, why hasn't it been done yet? If you had a spare $1.5B, would you buy mnkd and do it yourself?
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Post by agedhippie on Aug 14, 2023 9:47:04 GMT -5
... Mike has already told us the preliminary numbers from India are in the 1.5 - 2% A1c reduction range. If true he should have some ammo for the T2 SoC and should be able to enlist the CGM vendors for support. I can't do Mike's job for him. Step 1 is getting the pre auths for 2024 removed. Step 2 is leveraging the India results to justify T2 SoC changes. Step 3 is doing the glp1/afrezza study to provide a transition path. OK - now you say Mike can't make a phone call. Al has an issue. Mike may have a solution. Problem solved - I dropped Al a note so he is expecting Mike's call. Mike needs to stop wasting time and see if Victoza DPI works. Maybe Al has an interest in putting his molecules on TA, maybe not. If Victoza DPI works as you predict, "Touchdown". The issue is that if the HbA1c reduction is 1.5-2.0% then Mounjaro already exceeds that. Consequently the ADA will see an India result like the one mentioned as confirmation of their current strategy and the SoC will remain unchanged. I would be very surprised if the CGM makers got involved, they are not about to burn political capital on a lost cause - even after India there is not enough supporting data to get a change. Of course Mike can make a phone call, anyone can make a phone call. Your note never made it to Bourla (unless it was hand delivered). The best case is that the people handling his mail will have routed it to someone in the GLP-1 team, but more likely it was just dumped with the hundreds of similar items they get daily. So when Mike phones his call will get handled exactly like all the other cold sales calls. Let us be clear on this - my expectation is that Victoza on TS will have exactly the same side effects as subq Victoza. Victoza is not GLP-1, it's GLP-1 analog with the side effects that come with that regardless of if it's inhaled, swallowed, or injected. By all means spend the money finding that out, but my suspicion is that Mike already knows this from his background. |
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Post by agedhippie on Aug 14, 2023 9:58:05 GMT -5
One thing I don't understand about this thread and similar threads. I'm just making up numbers to make a point. If a one time spend of $30M for clinical studies will lead to making $2B per year, why hasn't it been done yet? If you had a spare $1.5B, would you buy mnkd and do it yourself? Because there will be a team whose role is to pick where to invest their limited funds. This track doesn't look like a winner simply because of how GLP-1 analogs work, and the delivery isn't going to affect that. Contrast that with nintedanib where the byproduct of the breakdown of the drug in the gut causes side effects which an inhaled version would avoid and it's clear why that is in the pipeline and GLP-1 isn't. |
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Post by sayhey24 on Aug 14, 2023 15:13:44 GMT -5
One thing I don't understand about this thread and similar threads. I'm just making up numbers to make a point. If a one time spend of $30M for clinical studies will lead to making $2B per year, why hasn't it been done yet? If you had a spare $1.5B, would you buy mnkd and do it yourself? Because there will be a team whose role is to pick where to invest their limited funds. This track doesn't look like a winner simply because of how GLP-1 analogs work, and the delivery isn't going to affect that. Contrast that with nintedanib where the byproduct of the breakdown of the drug in the gut causes side effects which an inhaled version would avoid and it's clear why that is in the pipeline and GLP-1 isn't. Agreed - its all about resource availability. Mike spent what he had on the kids study, inhale-2 and inhale-3. Then we have 101, 201, 301 and 501. He also spent $15M on V-Go. On Monday he said he can now do a few more pilots. He has already mentioned the glp1/afrezza pilot. I am hoping thats already moving. uvula - As far as TS GLP1 he was not aware MNKD had done a good amount of work on it years ago. He also viewed it as a T2 product not a diet product. For a T2 product removing the shot is a me too product. What Pfizer has told us is removing the shot in the diet market opens a $90B market. Is Pfizer correct? I think they are and that's why I think we see "Ozempic Shaming". Aged argues removing the shot will make no difference. For the diet market I think removing the shot is huge and a brand new tiktoc campaign. Now that Mike said last Monday we have some resources for a few more pilots I would like him to do the glp1/afrezza and Victoza DPI pilot. Of course I would have liked to see these last year before the money was spent on V-Go. As far as 101,201, 301 and 501 these pilots should have zero impact on them moving forward. This is not a zero sum game. Then again the IPF market potential is about $4B for nintedanib and not $90B. |
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Post by agedhippie on Aug 14, 2023 19:17:26 GMT -5
... What Pfizer has told us is removing the shot in the diet market opens a $90B market. Is Pfizer correct? I think they are and that's why I think we see "Ozempic Shaming". Aged argues removing the shot will make no difference. For the diet market I think removing the shot is huge and a brand new tiktoc campaign. Now that Mike said last Monday we have some resources for a few more pilots I would like him to do the glp1/afrezza and Victoza DPI pilot. Of course I would have liked to see these last year before the money was spent on V-Go. As far as 101,201, 301 and 501 these pilots should have zero impact on them moving forward. This is not a zero sum game. Then again the IPF market potential is about $4B for nintedanib and not $90B. If you actually read the transcript of the call what Pfizer told us was that the entire GLP-1 market will be worth $90B. He expects the the oral market to be a maximum of $30B of which Pfizer wants a third, and by oral he is referring to pills. There is no reason for Pfizer to be interested in inhaled GLP-1 as they already have a pill version. |
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