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Post by cretin11 on Jan 20, 2024 22:01:31 GMT -5
Thank you Bill for believing in Afrezza and doing as much (or more) as any other person to get it into the lungs of PWDs.
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Post by lennymnkd on Jan 21, 2024 10:24:27 GMT -5
While we’re at it 😀sports : Bill and Mike can’t co-opt $$$ some local advertising to see what works for the
Bigger picture.. seems like you would be the perfect people to test market and get a feel for things.
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Post by uvula on Jan 21, 2024 11:05:29 GMT -5
Bill said " At least that is my belief and one I intend to prove with data in time.”
He can convince himself based on the results he sees in his patients. That is, he can prove it to himself and Mannkind followers. But unless he is conducting an actual FDA approved clinical trial, no one "important" will consider his results to be proof of anythng.
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Post by sayhey24 on Jan 21, 2024 11:09:31 GMT -5
You are missing the point - its not about making money. Its about breaking the insurance blockade and establishing the base. The $35 campaign only makes sense if the Cipla and kids trial data is a good as Mike has signaled. If they are then we have solved the multi-year Proboards discussion that afrezza does not have the "data" for doctors to prescribe. You also never give anything away for free which has value and afrezza has value. Even if you have people pay $1 that is significantly different than "free". Even in the days of AOL you got the CD for free but then you had to pay the $5 per month. Is $35 the right number IDK. Maybe its a little more or less but $35 is the current Medicare price for insulin. Its also the number Mark Cuban promised for CostPlusDrugs. From an ongoing business perspective, as long as BP has afrezza at 1k scripts afrezza is really not worth perusing. If it were not for Tyvaso DPI paying for the factory afrezza at 1k scripts a week even at the current $1000 a box pricing is a money loser. Even a bigger question for you is do you agree with Bill from VDex and think afrezza should be prescribed first or do you think the current T2 SoC is the right way to go? It has to be about making money when you're a publicly traded company not named Amazon. Let's say you build up the base for 50,000 people to get on Afrezza. What makes you think insurance is going to want to turn around and increase reimbursement from $35 to $1000 if they even decide to cover the patient going forward? I'd much rather they spend that minimum of $25 million of losses over a couple years designing a bomb ass study so they can actually continue getting the $1000 they're currently asking and then quickly turn 1000 weekly scripts into 50,000 once they become standard of care- if we're so sure the data will undeniably suggest that. To answer the last question- I honestly don't know. I don't really do any of my own research. I have to trust that the ones that do have done a good job. I can tell you I want to think like Bill does. I have some pretty amazing stories from diet/exercise, metformin, and Mounjaro all as monotherapy. Every one of those modalities got my patient from an A1c greater than 11 to putting their diabetes in remission. It's really hard to develop an informed decision when there isn't more than anecdotal evidence on Afrezza. I have just as many anecdotes with other medications. Do they stop the PPGE as well as Afrezza? No. But they also last longer and reduce the basal sugar better. The true SOC should be diet and exercise first, but no one really does that, so we throw medications at them. Sports posted a nice response from Bill above. In a general sense the best approach is diet/exercise plus afrezza. For glucose control Mounjaro really has no place since what you really want to do is help the body replicate natural function. If you are looking for weigh reduction Mounjaro plus afrezza makes sense. With afrezza right or wrong we have been playing the long game for 9 years and we will continue to play it for another two years. Here is why. Three things need to be fixed for broad based afrezza adoption and that is going to take 2 years. They are 1. The label 2. The SoC 3. The cost We can not fix the label nor the SoC until we have the Cipla results and the kids results. I am assuming both will be great and they should provide the "bomb ass" study results you have asked for. Bill also mentioned they are working with the university in New Mexico to a do clinical study and lets hope we get some "bomb ass" results from that. The reality is we are not going to get broad based sales at the $1000 a box price until we get insurance coverage. We are not going to get that until we have fixed the SoC. We are not fixing either the label nor SoC in 2024. This will take 2 more years. The only doctors who are going to actively prescribe afrezza during the next 2 years are those that really understand afrezza and are ignoring the label and have developed their own SoC and are willing to fill out the pre auth and other paperwork for insurance. VDex for example knows how to dose and they have developed their own SoC. What stops VDex from prescribing afrezza today is cost. Their patients can not afford it. The only thing which MNKD can do in 2024 to directly impact scripts is price. Mike's current plan is the old "four corner delay" to run out the clock for the next 2 years. During this time we will continue to see slow script growth. The risk we run is in 2026 we don't have the base and did not hire the right lobbyists and "inhaled insulin" again ends up in parentheses in the SoC. If that happens we will not get the proper insurance coverage. Expanding the base over the next two years mitigates that risk. You mentioned metformin above. My favorite quote of all time is from the "Father of metformin" To put it in context Ralph was the leading guy to get metformin FDA approved and as step 1 in the SoC until BP came in with GLP1 money for Ralph - from Ralph “The most waste in type 2 diabetes is to continuously put people on metformin and sulfonylureas (glyburide, glimepiride, etc.). These drugs have no protective effect on the beta cell, and by the time you figure out what you’re doing, there are no beta cells left to save.” – Dr. Ralph DeFronzo (University of Texas Health Science Center) diatribe.org/the-diatribe-foundation-and-tcoyd-11th-annual-forum |
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Post by agedhippie on Jan 21, 2024 12:53:03 GMT -5
Sports posted a nice response from Bill above. In a general sense the best approach is diet/exercise plus afrezza. For glucose control Mounjaro really has no place since what you really want to do is help the body replicate natural function. If you are looking for weigh reduction Mounjaro plus afrezza makes sense. ... And yet here we are because Novo Nordisk and Lilly have done the work to prove that GLP-1 and GLP-1/GIP work. The A1c reduction for Mounjaro in large clinical trials is higher than the top end that Mike is quoting for the CIPLA trial. At this point the argument is usually that HbA1c is outdated, but it's also still the gold standard because it can be directly tied to outcomes and outcomes are what matters. The same as always; do the work or don't expect change. In this case the work is a trial for T2 adopting the SURPASS format but with Afrezza as one of the arms. That gives direct comparison to basal only, Ozempic, and Mounjaro. That's how you change the SoC, not with limited time special offers on Afrezza. |
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Post by agedhippie on Jan 21, 2024 13:07:41 GMT -5
Two thoughts from Bill pertaining to different parts of this overall conversation. “1) I don’t think insurers will ever voluntarily cover Afrezza bc that’s not how those businesses function. But great data showing the superiority of Afrezza will FORCE the insurers to cover, especially for people who have prolonged lack of BG control. 2) regarding the use of Afrezza as first AND SOLO therapy, I start from the premise that the best therapy is one that manages BG as close as possible to the way the body does naturally. Intuitively it makes sense that such a strategy will lead to better control and fewer side effects. Afrezza is as close as one can get to what the body does naturally in managing glucose levels. One good example: the body doesn’t make basal insulin. Basal insulins are synthetic. They have value but they have side effects. Afrezza is essentially identical to pancreatic insulin and therefore works the same with no major side effects. In fact with Afrezza we see true disease reversal something we don’t see with other therapies. That’s why it should be used first: catch diabetes at the early stage with Afrezza and you can eliminate the disease. At least that is my belief and one I intend to prove with data in time.” Bullet 1; absolutely. Trial data to show markedly better outcomes will do it - look at the transition from human insulin to RAA. It will also not be quick. Bullet 2; insulin will always work where there is a deficiency, either absolute in the case of T1, or effective in the case of T2, and you are addressing the deficiency. The argument that the body doesn't make basal insulin is right in the literal sense (it only makes human insulin), but wrong in the effect. As a background process the body continually outputs glucose for energy (breathing, brain function, etc.) and insulin to utilize that glucose, this is also how pumps handle basal insulin. Basal insulin analogs like Tresiba replace that continuous insulin output and lets the body save it's own insulin for meal time. What Bill is doing is turning that around and using Afrezza for meal times which leaves the body's insulin to handle basal. Historically it has been done the other way around because handling basal doesn't require many smarts (there are fluctuations during the day, but these are slow) and it was considered better to have the body's insulin handle meals since the body continuously adjusts in real time to the glucose levels rather than being a one time event. Proving Afrezza can handle that role would be big. |
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Post by sayhey24 on Jan 21, 2024 14:20:23 GMT -5
Sports posted a nice response from Bill above. In a general sense the best approach is diet/exercise plus afrezza. For glucose control Mounjaro really has no place since what you really want to do is help the body replicate natural function. If you are looking for weigh reduction Mounjaro plus afrezza makes sense. ... And yet here we are because Novo Nordisk and Lilly have done the work to prove that GLP-1 and GLP-1/GIP work. The A1c reduction for Mounjaro in large clinical trials is higher than the top end that Mike is quoting for the CIPLA trial. At this point the argument is usually that HbA1c is outdated, but it's also still the gold standard because it can be directly tied to outcomes and outcomes are what matters. The same as always; do the work or don't expect change. In this case the work is a trial for T2 adopting the SURPASS format but with Afrezza as one of the arms. That gives direct comparison to basal only, Ozempic, and Mounjaro. That's how you change the SoC, not with limited time special offers on Afrezza. Yes both Novo and Lilly have proven GLP-1s work and as Mike has said for about 2 years. GLP-1s do not address the root cause which is the body is not making enough insulin which can be used by the body. I am not sure if you are now moving the goal posts when it comes to the Cipla results. Are you suggesting this study won't be good enough to make imapcts to the SoC? |
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Post by sayhey24 on Jan 21, 2024 14:34:18 GMT -5
Two thoughts from Bill pertaining to different parts of this overall conversation. “1) I don’t think insurers will ever voluntarily cover Afrezza bc that’s not how those businesses function. But great data showing the superiority of Afrezza will FORCE the insurers to cover, especially for people who have prolonged lack of BG control. 2) regarding the use of Afrezza as first AND SOLO therapy, I start from the premise that the best therapy is one that manages BG as close as possible to the way the body does naturally. Intuitively it makes sense that such a strategy will lead to better control and fewer side effects. Afrezza is as close as one can get to what the body does naturally in managing glucose levels. One good example: the body doesn’t make basal insulin. Basal insulins are synthetic. They have value but they have side effects. Afrezza is essentially identical to pancreatic insulin and therefore works the same with no major side effects. In fact with Afrezza we see true disease reversal something we don’t see with other therapies. That’s why it should be used first: catch diabetes at the early stage with Afrezza and you can eliminate the disease. At least that is my belief and one I intend to prove with data in time.” Bullet 1; absolutely. Trial data to show markedly better outcomes will do it - look at the transition from human insulin to RAA. It will also not be quick. Bullet 2; insulin will always work where there is a deficiency, either absolute in the case of T1, or effective in the case of T2, and you are addressing the deficiency. The argument that the body doesn't make basal insulin is right in the literal sense (it only makes human insulin), but wrong in the effect. As a background process the body continually outputs glucose for energy (breathing, brain function, etc.) and insulin to utilize that glucose, this is also how pumps handle basal insulin. Basal insulin analogs like Tresiba replace that continuous insulin output and lets the body save it's own insulin for meal time. What Bill is doing is turning that around and using Afrezza for meal times which leaves the body's insulin to handle basal. Historically it has been done the other way around because handling basal doesn't require many smarts (there are fluctuations during the day, but these are slow) and it was considered better to have the body's insulin handle meals since the body continuously adjusts in real time to the glucose levels rather than being a one time event. Proving Afrezza can handle that role would be big. The reason insulin has historically not be given at meal time is for three reasons 1. fewer injections the better - no one likes needles 2. hypoglycemia risk - even with the RAAs 3. they didn't have afrezza What Bill is outlining is the medically correct way to treat T2 diabetes. In addition to stopping the spike and getting the BG back to baseline asap it also stops hyperinsulinemia and resyncs the liver. If afrezza was around 50 years ago it would be the T2 SoC today. Then again there would not be a $100B industry pumping out all the antiglycemics. The SoC would be pretty simple and not the Rube Goldberg it is today - 1. diet and exercise for "prediabetics" 2. diet and exercise and afrezza for those with A1cs greater than 6.5. |
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Post by agedhippie on Jan 21, 2024 15:47:08 GMT -5
... I am not sure if you are now moving the goal posts when it comes to the Cipla results. Are you suggesting this study won't be good enough to make imapcts to the SoC? As I have said before but you don't ever remember; (1) they are a rerun of the T2 phase 3 trial MNKD did, and (2) probably more importantly Mounjaro already gets HbA1c reductions of greater that 2.0%. So why exactly do you think CIPLA will change the SoC?  |
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Post by letitride on Jan 21, 2024 16:14:43 GMT -5
Why is India duplicating a trial already done?
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Post by sayhey24 on Jan 21, 2024 17:54:21 GMT -5
Why is India duplicating a trial already done? They took the 175 protocol because it was a proven protocol with the exception of how afrezza was to be dosed and hopefully the addition of GLP1s which did not exist when the 175 was done. The key to this study is properly dosing afrezza. We know from the ADCOM what happened when afrezza was properly dosed. The results were so good the FDA review team accused the doctor who had his patients do follow-up dosing of cheating. When asked why he did not follow-up dose the RAA he looked at the FDA lady and said "because I would have killed my patients". In the 175 you are given afrezza or a placebo. Its is used alone and also added to other antiglycemics. If it provides non-inferior results to Mounjarno then it should be added as a step 2 alternative and that should be good enough for T2 insurance coverage and Medicare coverage. Lots of ifs but if they get Medicare without pre-auths and a step 2 designation Abbott and DXCM now have an interest in seeing it prescribed. However, if they get an SoC step 2 designation then it messes up current BP plans. Abbott for example is banking on getting Medicare T2s on icodec which is step 4. Then again to this point they have written off afrezza as it has no insurance coverage The thing with icodec is with afrezza they are like peanut butter and jelly and you can see it with the CGM. The problem the T2 has is post prandial control. Mounjaro provides no benefit here but afrezza kicks butt. Now if afrezza and Mounjaro are the same at A1c but afrezza shows via CGM what Mounjaro can't do, afrezza wins. Then again if you are looking for weight loss then you want the Zepbound and afrezza. Of course we don't have an even playing field and we have the magic hand of BP tipping the scales as the last thing they want is afrezza making problems and disrupting the $100B industry. |
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Post by uvula on Jan 21, 2024 18:05:54 GMT -5
Why is India duplicating a trial already done? Much shorter answer than the previous one: The Cipla trial is for India. Cipla is paying for it to get approval in India. Cipla probably couldn't care less about afrezza sales in the USA. |
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Post by agedhippie on Jan 21, 2024 18:45:41 GMT -5
^What he said.
The CDSCO rejected Cipla’s application to sell Afrezza without a local trial and required a trial. The quickest and easiest way to fix that is replicated the US phase 3 trial which is what they are doing.
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Post by bthomas55ep on Jan 21, 2024 19:08:21 GMT -5
^What he said. The CDSCO rejected Cipla’s application to sell Afrezza without a local trial and required a trial. The quickest and easiest way to fix that is replicated the US phase 3 trial which is what they are doing. As CIPLA did not appear in Mike's JP Morgan Slides and Mannkind/Afrezza did not seem to appear anywhere in the recent CIPLA update/projection/pipeline slides, is anyone aware of whether or not CIPLA is even still working on approval of inhaled insulin? Any thoughts? |
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Post by stevil on Jan 21, 2024 21:48:05 GMT -5
Mounjaro fixes the underlying problem of insulin sensitivity and takes no work by the person using it.
Healthiest? Diet and exercise, then Afrezza.
Most likely to succeed in reducing A1c with minimal effort and potentially no lifestyle change? Mounjaro.
I’m not necessarily disagreeing with Bill. I just have a different vantage point because I have only gotten 1 newly diagnosed type 2 diabetic on Afrezza, whereas VDex gets nearly all of their newly diagnosed patients on Afrezza.
I also don’t get any newly diagnosed type 2s except that one Afrezza user, so take my words with a different grain of salt. So while I don’t get to see CGM miracles all the time, I do see many patients successfully put their diabetes in remission without Afrezza. So I’d like to see it play out on a bigger scale to avoid statistical anomalies and selection biases.
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