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ADA
Jun 27, 2018 20:36:25 GMT -5
Post by agedhippie on Jun 27, 2018 20:36:25 GMT -5
I would argue that Afrezza should be added to bullet 2 on the basis of the Phase 3 trial (the trial found that RAA and Afrezza performed equally). Same argument for Type 2 treatment, there is an equivalence established. Six months seems a reasonable time to get it done. There is no way they make Afrezza a preferred treatment without a superiority trial. This is evidence based medicine and the classification matrix for evidence is clear on what is required (I feel we have had this evidence discussion before). That said 18 months is long enough to set up and run that trial so it's not an unreasonable timeframe. I suspect what the ADA will do is change all references to rapid acting insulin analogs or injections to simply rapid acting insulin. That would then cover both injected and inhaled insulin. Aged - I sure hope you saw today's presentation.
Dr. Kendall seems to disagree with you on pretty much everything you said above. He called afrezza a "superior" insulin. He also said he already has more than enough studies to make things happen. Most interesting he said not making afrezza the standard of care would be both a moral issue and medical mistake. I was really surprised he pulled the moral card.
Dr. Kendall seems to have fire in the belly and is going to make things happen. Just as the standard of care for all MDI prior to RAA, whats that worth? I would say $1B. Assuming 200M outstanding shares, 50% margin and a P/E of 30, whats the share price at?
I have posted this before, but to save everyone from going back and digging it out here this is how the ADA grades evidence for the standard of care. Almost all of the standard of care is based exclusively on grade A or B. If you cannot meet those grades you are not going to get a change. A) - Clear evidence from well-conducted, generalizable randomized controlled trials that are adequately powered, including: - Evidence from a well-conducted multi-center trial - Evidence from a meta-analysis that incorporated quality ratings in the analysis - Compelling non-experimental evidence, i.e., “all or none” rule developed by the Centre for Evidence-Based Medicine at the University of Oxford - Supportive evidence from well-conducted randomized controlled trials that are adequately powered, including: - Evidence from a well-conducted trial at one or more institutions - Evidence from a meta-analysis that incorporated quality ratings in the analysis B) - Supportive evidence from well-conducted cohort studies - Evidence from a well-conducted prospective cohort study or registry - Evidence from a well-conducted meta-analysis of cohort studies - Supportive evidence from a well-conducted case-control study C) - Supportive evidence from poorly controlled or uncontrolled studies - Evidence from randomized clinical trials with one or more major or three or more minor methodological flaws that could invalidate the results - Evidence from observational studies with high potential for bias (such as case series with comparison with historical controls) - Evidence from case series or case reports - Conflicting evidence with the weight of evidence supporting the recommendation E) - Expert consensus or clinical experienceNow, can he get Afrezza into the Standard of Care? Yes I think so, and 6 months is not an unreasonable timescale. Can he displace RAA as THE Standard of Care? Not as things stand. The only usable trial is a non-inferiority trial so that isn't going to do it by definition. STAT would not work because it is inadequately powered (short duration, small sample set). I will happily take a bet, say 100 MNKD shares, that he does not get to displace RAA with Afrezza before the end of the year. There is zero chance because the trial data to meet the evidence criteria is not there.
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Post by bill on Jun 27, 2018 21:02:55 GMT -5
Aged - I sure hope you saw today's presentation.
Dr. Kendall seems to disagree with you on pretty much everything you said above. He called afrezza a "superior" insulin. He also said he already has more than enough studies to make things happen. Most interesting he said not making afrezza the standard of care would be both a moral issue and medical mistake. I was really surprised he pulled the moral card.
Dr. Kendall seems to have fire in the belly and is going to make things happen. Just as the standard of care for all MDI prior to RAA, whats that worth? I would say $1B. Assuming 200M outstanding shares, 50% margin and a P/E of 30, whats the share price at?
I have posted this before, but to save everyone from going back and digging it out here this is how the ADA grades evidence for the standard of care. Almost all of the standard of care is based exclusively on grade A or B. If you cannot meet those grades you are not going to get a change. A) - Clear evidence from well-conducted, generalizable randomized controlled trials that are adequately powered, including: - Evidence from a well-conducted multi-center trial - Evidence from a meta-analysis that incorporated quality ratings in the analysis - Compelling non-experimental evidence, i.e., “all or none” rule developed by the Centre for Evidence-Based Medicine at the University of Oxford - Supportive evidence from well-conducted randomized controlled trials that are adequately powered, including: - Evidence from a well-conducted trial at one or more institutions - Evidence from a meta-analysis that incorporated quality ratings in the analysis B) - Supportive evidence from well-conducted cohort studies - Evidence from a well-conducted prospective cohort study or registry - Evidence from a well-conducted meta-analysis of cohort studies - Supportive evidence from a well-conducted case-control study C) - Supportive evidence from poorly controlled or uncontrolled studies - Evidence from randomized clinical trials with one or more major or three or more minor methodological flaws that could invalidate the results - Evidence from observational studies with high potential for bias (such as case series with comparison with historical controls) - Evidence from case series or case reports - Conflicting evidence with the weight of evidence supporting the recommendation E) - Expert consensus or clinical experienceNow, can he get Afrezza into the Standard of Care? Yes I think so, and 6 months is not an unreasonable timescale. Can he displace RAA as THE Standard of Care? Not as things stand. The only usable trial is a non-inferiority trial so that isn't going to do it by definition. STAT would not work because it is inadequately powered (short duration, small sample set). I will happily take a bet, say 100 MNKD shares, that he does not get to displace RAA with Afrezza before the end of the year. There is zero chance because the trial data to meet the evidence criteria is not there. agedhippie - Might not Dr. K try to play the card that it's malpractice to allow T2's insulin producing beta cells to die off for lack of insulin when there's Afrezza, a safe enough insulin when used with a CGM to avoid the one significant downside of hypos? And, use that claim to become THE Standard of Care for T2's. That wouldn't need any type of studies. It's just simple science and common sense .
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ADA
Jun 27, 2018 22:25:14 GMT -5
Post by agedhippie on Jun 27, 2018 22:25:14 GMT -5
- Might not Dr. K try to play the card that it's malpractice to allow T2's insulin producing beta cells to die off for lack of insulin when there's Afrezza, a safe enough insulin when used with a CGM to avoid the one significant downside of hypos? And, use that claim to become THE Standard of Care for T2's. That wouldn't need any type of studies. It's just simple science and common sense . Without a major supporting trial that claim would fall under grade E evidence - expert consensus or clinical experience. You really need grade A or possibly B evidence for a major change. The other issue would be that it's far from decided science that this would work. There are a lot of papers around this, but also a host of other theories on Type 2. Dr K alluded to that on the call today when he was talking about asking his colleague what caused Type 2. Early insulin seems to help, but does it help in all cases or just some? Equally anything that reduces hyperglycemia and not just insulin is likely to help because that relieves the oxidative stress that kills beta cells (one theory). What we do know is that remission with insulin (or other non-insulin drugs) is possible, however in the end it seems to always relapse. Unfortunately that is the story with pretty much all treatments for Type 2. Essentially to make this change would say that the root cause of Type 2 is beta cell death due to hyperglycemia, nobody is ready to say that.
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Post by uvula on Jun 28, 2018 3:01:35 GMT -5
Getting off topic slightly, but it sounds like afrezza makes it possible to conduct some important medical studies that could fundamentally improve diabetes treatment. Shouldn't the ADA, the NIH, and similar organizations be funding and conducting these studies instead of making mnkd do all the heavy lifting? Could the small STAT study be compelling enough to convince independent doctors to design and conduct their own studies?
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Post by sayhey24 on Jun 28, 2018 4:39:27 GMT -5
- Might not Dr. K try to play the card that it's malpractice to allow T2's insulin producing beta cells to die off for lack of insulin when there's Afrezza, a safe enough insulin when used with a CGM to avoid the one significant downside of hypos? And, use that claim to become THE Standard of Care for T2's. That wouldn't need any type of studies. It's just simple science and common sense . Without a major supporting trial that claim would fall under grade E evidence - expert consensus or clinical experience. You really need grade A or possibly B evidence for a major change. The other issue would be that it's far from decided science that this would work. There are a lot of papers around this, but also a host of other theories on Type 2. Dr K alluded to that on the call today when he was talking about asking his colleague what caused Type 2. Early insulin seems to help, but does it help in all cases or just some? Equally anything that reduces hyperglycemia and not just insulin is likely to help because that relieves the oxidative stress that kills beta cells (one theory). What we do know is that remission with insulin (or other non-insulin drugs) is possible, however in the end it seems to always relapse. Unfortunately that is the story with pretty much all treatments for Type 2. Essentially to make this change would say that the root cause of Type 2 is beta cell death due to hyperglycemia, nobody is ready to say that.
What we do know from 60 years of study is insulin works in all cases. In the few it does not the PWD dies. While we may now know the causes there is a pretty good chance we are not going to be able to stop it being viral based. However, we do know that by taking the load off the pancreas, if there is not significant beta cell damage, we can not only stop the progress but we do see beta cell regeneration. Yes, T2 diabetes can be reversed in some cases. The key is treating the "Prediabetics" and early stage diabetics ASAP and the treatment is simple; a daily walk; lose a few pounds; and take the afrezza. The other key is if the PWD is under an active viral attack and how the immune system is dealing with it. For the active attacks the best we can do is treat the symptom with afrezza and hope the immune system kicks in. It often does.
What we also know is that since UpJohn's marketing efforts in the 1950's insulin has been delayed and delayed and delayed to the detriment of the PWD and the benefit of the Pharma's selling antiglycemics. Dr. Kendall had a great slide yesterday showing the antiglycemics really have had no medical value. What we also know based on breaking news yesterday by Dr. Kendall is he can scientifically show afrezza is not GrandMa's insulin but it is a Superior insulin. It is the greatest advance in diabetes care since 1922.
Now, you keep saying we need more studies. What Dr. Kendall said yesterday was he has enough data from the studies which have been done. One of you is right and we should know in the coming months. However, if I was a betting man my money is with Dr. Kendall. Understand, its nothing personal but Dr. Kendall has a history of knowing what he is doing.
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Post by akemp3000 on Jun 28, 2018 5:30:40 GMT -5
Well said Sayhey. If this was a court trial, Dr. Kendall proved at the investor conference that he would be walking into court with the facts and Afrezza would quickly become the standard of care. No wonder he left Lilly to join little Mannkind. Since it's not a court trial, we can only hope Dr. Kendall and the new Scientific Advisory Board, which he said consists of 9 of the top 20 thought leaders in the world, can capture the attention of the ADA and others needed for change. The data already exists. 45 new diabetes drugs in the past ten years with little significant results is a powerful rebuke of the current standards of care. No doubt, the big three BPs will be aggressively trying to slow him down. This is a war that diabetics must win. After hearing him yesterday my money is with Dr. Kendall also.
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Post by peppy on Jun 28, 2018 6:04:48 GMT -5
Getting off topic slightly, but it sounds like afrezza makes it possible to conduct some important medical studies that could fundamentally improve diabetes treatment. Shouldn't the ADA, the NIH, and similar organizations be funding and conducting these studies instead of making mnkd do all the heavy lifting? Could the small STAT study be compelling enough to convince independent doctors to design and conduct their own studies? As near as I can tell, it is our imaginations, moral upbringing and mis information that has us thinking these licensing organizations are here to help cure disease.
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Post by agedhippie on Jun 28, 2018 7:02:25 GMT -5
Getting off topic slightly, but it sounds like afrezza makes it possible to conduct some important medical studies that could fundamentally improve diabetes treatment. Shouldn't the ADA, the NIH, and similar organizations be funding and conducting these studies instead of making mnkd do all the heavy lifting? Could the small STAT study be compelling enough to convince independent doctors to design and conduct their own studies? Actually you are beginning to see that, the Yale study is an example. I think you will see Afrezza being used in studies to show the impact of faster insulin by universities like Yale and Colarado because studies are part of what they do.
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Post by mango on Jun 28, 2018 9:04:45 GMT -5
The issue with the ADA grading system is it has created SOC that is full of barbaric practices. The ADA's grading system is fundamentally flawed, as is most of the studies used to support their thinking (see: Metformin).
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Post by goyocafe on Jun 28, 2018 9:23:55 GMT -5
The issue with the ADA grading system is it has created SOC that is full of barbaric practices. The ADA's grading system is fundamentally flawed, as is most of the studies used to support their thinking (see: Metformin). I suspect Dr. Kendall’s word choices, “moral”, “ethical”, is intended to break the log jam at the ADA, which is more likely than not conflicted by the status quo and the funding that accompanies it.
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Post by lennymnkd on Jun 28, 2018 9:31:09 GMT -5
Get 60 minutes on the case !💪
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Post by sportsrancho on Jun 28, 2018 9:32:33 GMT -5
Mannkind's Afrezza
Mannkind was in the house with a booth for its inhaled insulin Afrezza, and as users ourselves, our team always likes seeing the giant Dreamboat inhaler on the display wall. Many more conference-goers seemed much more familiar with Afrezza than we recall in years past.
This year, Mannkind was showing off positive study results from its STAT and AFFINITY studies that looked at improved time in range and reduced hypoglycemia. The STAT study involved 60 type 1 patients and is the first randomized, controlled study to use CGM with Afrezza. Compared to injected insulin, and using "supplemental doses" of at 1 and/or 2 hours post-meal, Afrezza:
Significantly improved all-day glucose time-in-range by an average of 1.5 hours, or 12% Significantly decreased daytime glucose variability by 17% Significantly reduced the time spent in hypoglycemia (i.e., <70 mg/dl) by 41% or approximately 23 minutes per day The AFFINITY study, also with type 1s, showed that compared to injected insulin aspart, Afrezza:
Significantly lowers the rate of hypoglycemia in T1D while providing similar or better glycemic control (54.1 events per subject vs. 78.2 events per subject, a reduction of 31%) On average, shows 26% less hypoglycemia across a range of HbA1c levels, allowing the same degree of glycemic control with less hypoglycemia than insulin aspart This is of course just the kind of evidence the company needs to bump up provider confidence and therefore prescriptions.
Meanwhile, the company has kicked off a limited TV ad campaign and they hosted an investor and analyst meeting in New York City on June 27 (yesterday). They also held a diabetes blogger event a few months ago that brought them some nice coverage among the DOC patient community (our team was unable to attend, but as noted, we do use Afrezza ourselves).
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Post by mango on Jun 28, 2018 9:40:51 GMT -5
We see what's going on
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Post by lennymnkd on Jun 28, 2018 10:28:08 GMT -5
Mango , you are helping put that 60 minutes story together for them / good work 😀
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ADA
Jun 28, 2018 11:28:53 GMT -5
Post by mango on Jun 28, 2018 11:28:53 GMT -5
Here is this year's Endo Consensus. MannKind mentioned once. Just threw up a little from seeing all the folks sleeping w/ the Insulin Cartel.
CONSENSUS STATEMENT BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY ON THE COMPREHENSIVE TYPE 2 DIABETES MANAGEMENT ALGORITHM – 2018 EXECUTIVE SUMMARY
DISCLOSURES
Dr. Zachary Bloomgarden reports that he is a consultant for Sanofi, Merck, AstraZeneca, Intarcia, Novartis, and ProSciento. He is a speaker for Merck, AstraZeneca and Janssen. He owns stock with Allergan, Zimmer Biomet, and Novartis.
Dr. Daniel Einhorn reports that he is a consultant for Lilly, Novo Nordisk, Sanofi, Takeda, Halozyme, AstraZeneca, Adocia, Epitracker, GlySens, and Janssen. He is a speaker for Abbott. He owns stock with Halozyme and has options with Nexus BioPharma, Epitracker, and GlySens. He has also received research grant support from Novo Nordisk, Lilly, AstraZeneca, Janssen, and Sanofi.
Dr. Alan J. Garber reports that he is a consultant for Novo Nordisk and Intarcia.
Dr. Martin Julian Abrahamson reports that he is a consultant for Novo Nordisk, and WebMD Health Services.
Dr. Joshua I. Barzilay reports that he does not have any relevant financial relationships with any commercial interests.
Dr. Lawrence Blonde reports that he is a consultant for AstraZeneca, GlaxoSmithKline, Intarcia, Janssen, Merck, Novo Nordisk, and Sanofi. He is also a speaker for AstraZeneca, Janssen, Merck, Novo Nordisk, and Sanofi. Dr. Blonde has received research grant support from AstraZeneca, Janssen, Lexicon Pharmaceuticals, Merck, Novo Nordisk, and Sanofi.
Dr. Michael A. Bush reports that he is a consultant for Janssen and AstraZeneca. He is also a speaker for Eli Lilly, Novo Nordisk, Janssen, AstraZeneca, and Boehringer Ingelheim.
Dr. Samuel Dagogo-Jack reports that he is a consul tant for Merck, Janssen, AstraZeneca, and Sanofi. He owns stock with Dance Pharma and Janacare. He has also received research grant support to the University of Tennessee from AstraZeneca, Novo Nordisk, and Boehringer Ingelheim.
Dr. Ralph A. DeFronzo reports that he is a consultant for Boehringer Ingelheim, AstraZeneca, Novo Nordisk, Janssen, Intarcia, and Elcelyx. He is a speaker for Novo Nordisk, AstraZeneca, and Merck. He has also received grant research support from Bristol Myers Squibb, Boehringer Ingelheim, Janssen, and AstraZeneca.
Dr. Vivian A. Fonseca reports that he is a consultant for Takeda, Novo Nordisk, Eli Lilly, Pamlab, AstraZeneca, Abbott, Boehringer Ingelheim, Janssen, Intarcia, and Ashi Pharmaceuticals. He is a speaker for Sanofi and Takeda. He owns stock with Amgen. He has also received research grant support from Asahi, Abbott, and Bayer.
Dr. Jeffrey R. Garber reports that he does not have any relevant financial relationships with any commercial interests.
Dr. W. Timothy Garvey reports that he is a consultant for AstraZeneca, Janssen, Eisai, Takeda, Novo Nordisk, Alexion, and Merck. He has also received research grants from Merck, Weight Watchers, Sanofi, Eisai, AstraZeneca, Lexicon, Pfizer, and Novo Nordisk. Dr. Garvey is a shareholder in ISIS Pharmaceuticals, Novartis, Bristol Myers Squibb, Pfizer, Merck, and Eli Lilly.
Dr. George Grunberger reports that he has received speaker honoraria from Eli Lilly, BI-Lilly, Novo Nordisk, Sanofi, Janssen, and AstraZeneca. He has received research funding from AstraZeneca, Eli Lilly, Lexicon, Medtronic, and Novo Nordisk.
Dr. Yehuda Handelsman reports that he is a consultant for Amarin, Amgen, AstraZeneca, Boehringer Ingelheim (BI), Janssen, Eli Lilly, Eisai, Intarcia, Merck, Novo Nordisk, Sanofi, and Regeneron. He is a speaker for Amarin, Amgen, AstraZeneca, Boehringer Ingelheim- Lilly, Janssen, Novo Nordisk and Sanofi. He has also received research grant support from Amgen, AstraZeneca, Boehringer Ingelheim, Gan & Lee, Lexicon, Merck, Novo Nordisk, and Sanofi.
Dr. Irl B. Hirsch reports that he is a consultant for Abbott, Adocia, Intarcia, Bigfoot, and Roche. He has also received research grant support from Medtronic.
Dr. Paul S. Jellinger reports that he has received speaker honoraria from BI-Lilly, AstraZeneca, Novo Nordisk, Merck, Amgen, and Janssen.
Dr. Janet B. McGill reports that she is a consultant for Aegerion, Dexcom, Novo Nordisk, Intarcia, Valeritas, and Boehringer Ingelheim. She is a speaker for Aegerion, Dexcom, and Mannkind. She has received research grant support from Novartis, AstraZeneca, Bristol Myers Squibb, the Leona Helmsley Trust, and the National Institutes of Health.
Dr. Jeffrey I. Mechanick reports that he is a consultant for Abbott Nutrition International.
Dr. Paul D. Rosenblit reports that he is a consul- tant for Akcea Therapeutics/Ionis Pharmaceuticals, Amarin, Amgen, AstraZeneca, Novo Nordisk, and Sanofi- Regeneron. He is a speaker for AbbVie, Akcea Therapeutics/ Ionis Pharmaceuticals, Boehringer-Ingelheim, Bristol Myers Squibb/AstraZeneca, GlaxoSmithKline, Lexicon, Merck, Novo Nordisk, Roche, and Sanofi-Regeneron.
Dr. Guillermo E. Umpierrez reports that he is a consultant for Sanofi, Merck, and Glytec. He has also received research grant support to Emory University from AstraZeneca, Boehringer Ingelheim, Merck, Novo Nordisk, and Sanofi.
Amanda Justice reports she is a consultant for Lexicon.
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