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Post by Deleted on Aug 28, 2017 12:52:44 GMT -5
"I was a little disappointed when I read that latest abstract again. It says they used 29 males and 1 female; 29 were white and 1 was black. That's not a very representative population sample."
When I read such statements, I know shorts are worried.
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Post by straightly on Aug 28, 2017 13:26:45 GMT -5
"I was a little disappointed when I read that latest abstract again. It says they used 29 males and 1 female; 29 were white and 1 was black. That's not a very representative population sample." When I read posts with statements above, I know shorts are worried. I have a stock which I saw negative articles daily. I use their stretch as reasons to hold and trade when these negatives quite down. So far, it worked. 😁
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Post by thall on Aug 28, 2017 20:08:18 GMT -5
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Post by mnholdem on Aug 28, 2017 21:20:18 GMT -5
thallExcerpt from your first source: Results For a given body mass index, men were reported to have more lean mass, women to have higher adiposity. Men were also found to have more visceral and hepatic adipose tissue, whereas women had more peripheral or subcutaneous adipose tissue. These differences, as well as differences in sex hormones and adipokines, may contribute to a more insulin-sensitive environment in women than in men. When normalized to kilograms of lean body mass, men and women had similar resting energy expenditure, but physical energy expenditure was more closely related to percent body fat in men than in women.
Conclusion Greater amounts of visceral and hepatic adipose tissue, in conjunction with the lack of a possible protective effect of estrogen, may be related to higher insulin resistance in men compared with women.
--- It would appear that the data from this study is not really relevant. "Men were also found to have more visceral and hepatic adipose tissue, whereas women had more peripheral or subcutaneous adipose tissue." Afrezza utilizes pulmonary delivery, which bypasses the different types of tissue and delivers monomer insulin into the bloodstream. So it really doesn't matter whether you are male or female. The FDA will likely appreciate this key attribute. Regarding your second source related to greater insulin resistance among certain minority populations, I would agree with the study's conclusion that better methods should be found for controlling hyper- and/or hypo-glycemic excursions among populations with greater insulin resistance. This is where Afrezza will shine, since several studies currently exist which conclude that simulating the first phase insulin response (typical of a normal pancreas) has been demonstrated to lower insulin resistance. Afrezza would benefit by including those minorities that exhibit higher insulin resistance, provided the lowering of insulin resistance is one of the primary or secondary end points. That end point wasn't included in pre-market FDA trials, but could be a component of future post-market studies.
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Post by Deleted on Aug 28, 2017 21:42:37 GMT -5
mnholdem thanks for spending the time to read those articles and point out why they are irrelevant to the new label application.
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Post by sayhey24 on Aug 29, 2017 7:30:34 GMT -5
thall - I would say you really need to try harder as it sure seems you are badly loosing this argument. One of the great advantages of afrezza is you don't have all the traditional absorption issues which all RAAs have but afrezza doesn't. What I will say is every piece of FUD has been thrown at afrezza since 2008 and nothing is sticking. afrezza really is that good.
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Post by sportsrancho on Aug 29, 2017 9:10:39 GMT -5
Afrezza..the smart insulin. And then there's mnholdem...haven't you guys realized you can't out smart him:-)
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Post by thall on Aug 29, 2017 9:53:50 GMT -5
Excerpt from your first source: Results For a given body mass index, men were reported to have more lean mass, women to have higher adiposity. Men were also found to have more visceral and hepatic adipose tissue, whereas women had more peripheral or subcutaneous adipose tissue. These differences, as well as differences in sex hormones and adipokines, may contribute to a more insulin-sensitive environment in women than in men. When normalized to kilograms of lean body mass, men and women had similar resting energy expenditure, but physical energy expenditure was more closely related to percent body fat in men than in women.
Conclusion Greater amounts of visceral and hepatic adipose tissue, in conjunction with the lack of a possible protective effect of estrogen, may be related to higher insulin resistance in men compared with women.
--- It would appear that the data from this study is not really relevant. "Men were also found to have more visceral and hepatic adipose tissue, whereas women had more peripheral or subcutaneous adipose tissue." Afrezza utilizes pulmonary delivery, which bypasses the different types of tissue and delivers monomer insulin into the bloodstream. So it really doesn't matter whether you are male or female. The FDA will likely appreciate this key attribute. Regarding your second source related to greater insulin resistance among certain minority populations, I would agree with the study's conclusion that better methods should be found for controlling hyper- and/or hypo-glycemic excursions among populations with greater insulin resistance. This is where Afrezza will shine, since several studies currently exist which conclude that simulating the first phase insulin response (typical of a normal pancreas) has been demonstrated to lower insulin resistance. Afrezza would benefit by including those minorities that exhibit higher insulin resistance, provided the lowering of insulin resistance is one of the primary or secondary end points. That end point wasn't included in pre-market FDA trials, but could be a component of future post-market studies. Also from the first source: "Marked gender differences have been reported in regard to degrees of insulin resistance (in which a given concentration of insulin is associated with a subnormal glucose response), body composition, and energy balance."
Insulin resistance has nothing to do with the manner of drug delivery. There are also vast differences in the way men and women handle energy: www.ncbi.nlm.nih.gov/pmc/articles/PMC4890267/figure/F3/
And sex differences accounts for the difference in risk of type 2 diabetes between sexes: www.ncbi.nlm.nih.gov/pmc/articles/PMC4890267/table/T1/
And more than fat distribution is involved: journal.frontiersin.org/article/10.3389/fendo.2014.00241/full See under "Sex-Specific Differences in Glucose Metabolism and Insulin Action" and "Sex Hormones and Metabolism"
But it's hardly worth arguing about here since at this point it's in the hands of the FDA.
As far as "first phase insulin response," I believe it's been discussed here before: ajpendo.physiology.org/content/287/3/E371
"More importantly, a well-defined first phase is lacking under physiological conditions, i.e., when glucose is given orally...."
And that is illustrated in their graph: ajpendo.physiology.org/content/287/3/E371 The "square wave" represents what happens when glucose is given intravenously. Under normal conditions, glucose only rises gradually and doesn't provoke a "first phase" response.
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Post by dreamboatcruise on Aug 29, 2017 10:24:50 GMT -5
thall... At times I think certain people here don't even read what is presented. While I suspect management had a handle on FDA requirements and will get the label change, the points you present are valid and certainly haven't been refuted by this crowd as you presented info detailing that population gender/race variability is important to pharmacodynamics. I would still weigh in on the side of thinking it better from safety/efficacy standpoint to label Afrezza as faster, but if someone at FDA is trying to find a reason to deny the label change I could also see them latching onto this study population issue. I don't think any here including you is arguing the benefits of Afrezza (it's "that good"), but of course anyone that has a memory and isn't being totally disingenuous remembers that even for a drug "that good" we got 2 CRL's from the FDA... so it is ludicrous or pure spin to act like someone questioning how easy it is to get FDA approval for something must be trying to create FUD. Sorry people... getting things through the FDA is an uncertain process. They don't always get things right and at times even do things for very wrong reasons. I hope and believe the FDA will do the right thing this time, but Of course if the FDA for some reason chooses not to grant the label change as submitted, the crowd here will reiterate how good Afrezza is, say the label change doesn't matter and declare victory yet again as they always do.
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Post by sayhey24 on Aug 29, 2017 10:44:15 GMT -5
Thal - afrezza is dosage linear. Some people are more insulin resistant than others. The great part of a healthy pancreas is that it will produce more insulin for those people. How do we know this? Just check out via an autopsy the pancreas of an obese person who is insulin resistant. They grow all these new beta cell clumps.
Now the great part of afrezza is since its the exact same insulin that the pancreas produces, as Gary Sheiner says "think like a pancreas". What would a healthy pancreas do? Simply give them more insulin. Since afrezza reacts just like the healthy pancreas's insulin, no problem, Just don't try that with an old school RAA, it will probably kill the PWD.
You really need to try harder, mnholdem is smok'in you in this debate.
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Post by dreamboatcruise on Aug 29, 2017 11:13:01 GMT -5
Thal - afrezza is dosage linear. Some people are more insulin resistant than others. The great part of a healthy pancreas is that it will produce more insulin for those people. How do we know this? Just check out via an autopsy the pancreas of an obese person who is insulin resistant. They grow all these new beta cell clumps. Now the great part of afrezza is since its the exact same insulin that the pancreas produces, as Gary Sheiner says "think like a pancreas". What would a healthy pancreas do? Simply give them more insulin. Since afrezza reacts just like the healthy pancreas's insulin, no problem, Just don't try that with an old school RAA, it will probably kill the PWD. You really need to try harder, mnholdem is smok'in you in this debate. And you're totally missing the fact that FDA basis decisions on clinical data that is presented to them by the company seeking an approval. The FDA isn't going to consider autopsies or what Gary Sheiner has or hasn't said. Further, the FDA is people, and as we painfully have learned (if we have our memory intact), there is quite a lot of variability in the standards which can be applied to the suitability of the clinical data being presented. Have you even been following Mannkind/Afrezza since before the final CRL? Did you think the FDA would say the bridge study showing dreamboat was equivalent delivery mechanism to medtone would be found unacceptable? If you didn't then say Mannkind would get rejected, then you don't have a complete understanding of what constitutes irrefutable evidence in the FDAs eyes. If anyone steps forward and says (shows) they got that call right and they want to point out why Thall is wrong, that person I would then say won an argument... otherwise both sides are merely guessing about what the FDA may or may not regard as relevant by people that have little expertise or track record predicting such things. I now predict they will be granted the label change... but I incorrectly predicted they would get approval rather than the final CRL.
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Post by mango on Aug 29, 2017 12:38:47 GMT -5
Something essential to good health is called glucose homeostasis—tight regulation of blood sugar.
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Post by sayhey24 on Aug 29, 2017 12:56:41 GMT -5
According to the way the Chinese scientist bet with his money, many including most at the FDA thought afrezza should get approved on the second CRL. If it were not for a public complaint and corrupt leadership it would have. Fact is if it were not for corrupt leadership it would have gotten approved the first time and not rejected for cleaning procedures and graphics on the foil pack. And, I will bet my last penny that if it were not for the Adcom and the 27-1 vote it would not have been approved the third time.
Here is the simple fact, afrezza is not an RAA. It is not a Frankenstein insulin. It is the exact same insulin produced by the pancreas. The FDA does not require studies of the pancreas. We know how it works and what MNKD has shown is the afrezza "shockingly" profiles just like naturally released pancreatic insulin. What a surprise.
Now you want to talk FDA and standards - give me a break. Do you think Trulicity would ever have gotten approved if the FDA had standards??? They have politics and more politics and BP talks big with big money. One thing MNKD has going right now is Hamburg and her husband are gone so MNKD may have the most even playing field they have ever had. We also have good old Bernie Sanders still running around crying about BP and their insulin prices when he is not trying to keep his wife out of jail. So, maybe MNKD has a chance this time. Who knows as with the FDA its a crap shoot.
But - while they should get the "near natural" label things are changing. IMO the push is with big companies and wellness programs. These companies self fund their insurance. If it can be shown to these companies that they will save on health costs by giving IWatches to every employee like Aetna just announced, afrezza and its benefit will sell itself. There is little BP can do to stop it.
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Post by prosper on Aug 29, 2017 13:23:42 GMT -5
Whether anyone likes him or not, Trump has been pushing reform of FDA procedures and speed of evaluation. I don't think the FDA is going to fight a guy that has already begun the reform of the VA with such success. As a vet, I already see a difference and lo and behold, a deference by the people I have interacted with. They used to treat us as if we were at the DMV. Now there is a definite increase in service and respect.
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Post by dreamboatcruise on Aug 29, 2017 13:32:37 GMT -5
sayhey24... Afrezza is RHI insulin with however much importance one wishes to put on the differences between that and what is produced by the pancreas (produced by genetically modified organism, lacking c-peptide, consisting of only monomers not mix of mono and polymers as released by pancreas). When you say the FDA does not require studies of the pancreas... that is a statement beyond silly. Are you implying the FDA therefore hasn't or shouldn't regulate Afrezza? Well guess what, whether you wish it is was true or not, the FDA has regulated Afrezza and will continue to do so. I'd sell my entire MNKD stake and make a bet with you that you can never convince the FDA to side with you that Afrezza is so much like a pancreas that they don't need to treat it as any other drug that requires clinical evidence. There is no submittal for a "near natural" label. That is something you've made up.
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