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Post by prcgorman2 on Apr 23, 2019 19:36:16 GMT -5
Common sense, longer Mannkind survives the more disruptive. I been with Mannkind since 2008. Now I realize I won't make a profit on my investment. Just want my money back. Great product potential, worst Investment I have ever made. Wow. 11 years and less than 20 posts. Thanks for breaking radio silence. It must have been tough for you. I hope you won’t be offended if I comment that I really appreciate the average of your frequency of posting over that time and that I sincerely hope you continue along those lines.
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Post by prcgorman2 on Apr 23, 2019 19:49:47 GMT -5
Didn’t really follow your math there, but yes I agree that Afrezza is significantly faster acting than RAA and therefore easier to dose and stack if needed without the attendant same level of concern for hypoglycemia as RAA, and with a better quicker return to “normal” blood glucose levels therefore improving time in range, and A1C readings into the bargain. This is part of why I’m so enthusiastic about the future sucess for Mannkind shareholders, although I understand why FalconQuest dropped out (to maybe buy in again later - or otherwise why post here unless hIs believes he is trying to save potential future investors from a certain [in his mind] failure?).
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Post by letitride on Apr 23, 2019 19:55:59 GMT -5
What is RAA?
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Post by goyocafe on Apr 23, 2019 19:57:56 GMT -5
Without the pompoms, it's just an abbreviation that represents a rapid acting analog. Wiith them, it forms the basis of 90% of the cheers in the universe.
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Post by letitride on Apr 23, 2019 20:08:20 GMT -5
I believe the reason it takes more insulin human inhalation powder is because it is just that, and Im questioning what RAA is?
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Post by prcgorman2 on Apr 23, 2019 20:20:27 GMT -5
gogyocafe made me laugh out loud, seriously. Sorry, letitride, RAA (Rapid Acting Analog) was the fastest acting mealtime insulin on the market - until Afrezza came along.
RAA is an analog because it’s not human insulin. It’s insulin that’s been modified to improve it’s behavior after it’s injected into the subcutaneous tissues of the skin of the abdomen of a person with diabetes. It has a configuration that improves it’s durability as it’s absorbed into the bloodstream rather than breaking down into non-usable compounds before making it in usable quantities to the bloodstream for uptake by cells needing glucose. I’m not a doctor, and you’ll be well served to read more from someone who really knows what they’re talking about with respect to comparing human insulin (which is used in making Afrezza) with analog insulin which is used in making Humalog, Novolin, et cetera.
RAA is not bad mealtime insulin, but it’s nowhere near as fast acting and fast eliminatng from the body as Afrezza inhalable human insulin. Speed is important because diabetics don’t enjoy waiting to find out whether their blood glucose levels are in a good range or coming into a good range, or going high requiring stacking insulin injections or going low requiring eating sugar tablets or other sweet such as drinking orange juice. And if the blood glucose doesn’t come down and stays high or goes low and won’t come back up into a safe range, then rinse and repeat, more insulin injection into the abdomen, or more sweets to overcome the apparent overdose of RAA insulin. Waiting requires multiple blood samples over a longer period of time to see if their BG is rising too high or falling too low, or just fine. Think more finger pricks if the person with diabetes is not using a CGM, and less finger pricks to draw blood if they are using a CGM to ensure proper CGM calibration. Hopefully I didn’t muck that description up too badly and folks (like actual persons with diabetes which I’m not officially yet) can correct me as needed.
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Post by letitride on Apr 23, 2019 20:38:27 GMT -5
There is no comparison between RAA and afrezza, beyond they are both used in the treatment of diabetes. The rapid acting is lost in the fact its not even human insulin.
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Post by mango on Apr 23, 2019 20:42:36 GMT -5
That is more or less correct. In fact it was a statistician from the FDA who challenged the methodology of the Phase 3 trial, asking if it was right that the insulin dosage for Afrezza was higher than the dosage for the control arm, saying in effect, more insulin lower HbA1c. It was a doctor on the panel who pointed out that those higher dosages of an RAA could be fatal. The doctor was right. Afrezza uses a lot more insulin to achieve the same result as RAA because inhalation is not a particularly effective delivery route (a lot never makes it to where it needs to go). If you look at the dose sizes in the earlier trial you will see far bigger doses compared with later trials. That is because the dose sizes now reflect the action of RAA, and not the quantity of insulin used. This makes titration far easier as the numbers are more like people are used to. Even now the Afrezza dose is roughly 75% of an RAA dose. A few incorrect claims in your post, I noticed. First, the result is not the same with Afrezza and RAAs—not even close. Afrezza achieves the required serum insulin concentration within the required physiological time-boundary in order for it to effectively mimic the first-phase insulin release. Currently, no other insulin in the world that can do this besides Afrezza. ~70% of the inhalation powder reaches the deep lung, consistently, dose-to-dose—the same cannot be said for subq prandial insulins. Subq prandial insulin formulations have erratic, slow absorption. There is no similarities between Afrezza and RAAs, not even fundamentally—RAAs are not even insulin, they are altered foreign proteins. Afrezza is identical to human insulin, and also behaves like it. The same cannot be said for any other prandial insulin. The consequences of Afrezza mimicking endogenous first-phase insulin release are extraordinary—restoring post-prandial glucose homeostasis—a result in which no RAA, and no other insulin in the world, can currently achieve. Second, inhalation is a proven, effective route of administration. This is a demonstrable fact, with scientific literature abound, and so I will not comment further. Third, the dose sizes of Afrezza do not reflect the action of any RAA. The action of Afrezza is not similar to the action of any prandial insulin.
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Post by letitride on Apr 23, 2019 20:52:29 GMT -5
Maybe Afrezza should be marketed for what it is vs a rapid acting analog and people would understand when you're pancreas quits producing enough human insulin you inhale some to make up the difference vs RAA you know the stuff you got to question what it is.
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Post by uvula on Apr 23, 2019 23:35:11 GMT -5
Mango, is it correct to say that intravenous human insulin has the same pk profile as afrezza? Obviously you can't use IV therapy outside of a hospital, but it should be mentioned if we're trying to be extremely acurate in comparing insulins.
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Post by agedhippie on Apr 24, 2019 7:49:00 GMT -5
The doctor was right. Afrezza uses a lot more insulin to achieve the same result as RAA because inhalation is not a particularly effective delivery route (a lot never makes it to where it needs to go). If you look at the dose sizes in the earlier trial you will see far bigger doses compared with later trials. That is because the dose sizes now reflect the action of RAA, and not the quantity of insulin used. This makes titration far easier as the numbers are more like people are used to. Even now the Afrezza dose is roughly 75% of an RAA dose. A few incorrect claims in your post, I noticed. First, the result is not the same with Afrezza and RAAs—not even close. Afrezza achieves the required serum insulin concentration within the required physiological time-boundary in order for it to effectively mimic the first-phase insulin release. Currently, no other insulin in the world that can do this besides Afrezza. ~70% of the inhalation powder reaches the deep lung, consistently, dose-to-dose—the same cannot be said for subq prandial insulins. Subq prandial insulin formulations have erratic, slow absorption. There is no similarities between Afrezza and RAAs, not even fundamentally—RAAs are not even insulin, they are altered foreign proteins. Afrezza is identical to human insulin, and also behaves like it. The same cannot be said for any other prandial insulin. The consequences of Afrezza mimicking endogenous first-phase insulin release are extraordinary—restoring post-prandial glucose homeostasis—a result in which no RAA, and no other insulin in the world, can currently achieve. Second, inhalation is a proven, effective route of administration. This is a demonstrable fact, with scientific literature abound, and so I will not comment further. Third, the dose sizes of Afrezza do not reflect the action of any RAA. The action of Afrezza is not similar to the action of any prandial insulin. I think you may have a different line. The question was about the volume of insulin taken, not effectiveness. Afrezza simply takes a lot more insulin as shown by the trials (the jump between real insulin dose in earlier trials and scaled insulin dose in later trials), but really that doesn't matter at the end of the day.
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Post by ktim on Apr 24, 2019 13:28:29 GMT -5
Bad decisions in the past to grandfather things in doesn't justify continuing on with bad policy. It doesn't matter if a study proves Afrezza is superior, that isn't the issue. The issue is that people taking insulin should be under doctor's supervision. If insulin had been invented after FDA started regulating prescriptions then no insulin would be OTC. Hopefully we do get larger studies that show superiority and hopefully at levels greater than the 0.5% A1c difference shown in One Drop trial or doctors more quickly start paying attention to time in range. Regardless, the FDA is not going to make Afrezza OTC. If there were some fairness doctrine in play, I'd imagine they'd much sooner require prescriptions for humulin and novolin. Granted my stance on it being bad to have insulins OTC is based on a notion that people have access to doctors, which I know isn't always the case. But unwise to simply make everything OTC due to that issue. Ooh, now we've stumbled into an area where things really get interesting. I work with a bunch of people from other countries which do not have anywhere near the same restrictive regulatory practices. Not sure if they have an opioid epidemic and I wonder if Canada does where Tylenol3 is available OTC. Anyway, health care in general and medication too are both far cheaper. We know this too from our experience with Afrezza and Brazil and India expectations with respect to revenue.
As for "doctor supervision", how much supervision is there really? Most PWDs still don't have CGMs. And from what I can tell it is professional diabetes educators who provide the real care for self-treatment with insulin. That and other diabetics.
The more I think about it and the more we debate this, the more I think the case for Afrezza OTC improves.
Well, I'm a gambling man and would give you 10 to 1 odds against it. How much do you want to wager? I guess for practical purposes we'd need to set a date so the bet could be settled. Key thing is, we aren't a 3rd world country. I've been to countries where basically everything is OTC. We aren't headed in that direction. You are correct that physicians often utilize certified diabetes educators for the heavy lifting of patient education. Conceivable a pharmacist and on staff diabetes educator at a pharmacy could manage a patients care, but I don't see the business model working for the pharmacy. Additionally, doctors' unions are some of the strongest in the US. There are many things that are prescription only that have far smaller risk profiles than insulin, such as allergy medications. Doctors are good at rigging the system to protect their roll as gate keepers, even for these very safe drugs. I believe that more medications should be OTC (or behind counter with pharmacist consult), but not insulin. Anyway, I'll draw this conversation as to a close as you are only one of a long string to want to try to hype that to distract from reality. I don't need to prolong this discussion. Though as for wishful stories, yours kinda negates the more plausible on of pediatric approval moving the needle. In your scenario a parent would simply see their kid peeing too much, run down to the pharmacy and buy a BG meter. A finger stick later and back to the pharmacy to grab some Afrezza next to the cough syrup. Yikes!
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Post by ktim on Apr 24, 2019 13:59:17 GMT -5
Maybe Afrezza should be marketed for what it is vs a rapid acting analog and people would understand when you're pancreas quits producing enough human insulin you inhale some to make up the difference vs RAA you know the stuff you got to question what it is. Both RAA and "human insulin" are produced by genetically modified microorganisms into which human derived DNA has been inserted. Once Afrezza disassociates from the FKDP and RAA disassociates into monomers, they are chemically the same in the bloodstream. People here love to talk about this distinction in chemical composition, but most people that take these medications couldn't care less. Most diabetics that know about "human insulin" know that it as medium term acting insulin that really is poorly suited for much any purpose these days (when used as an injection). Marketing Afrezza as somehow special because of being "human insulin" would require marketing/education to distinguish from the long sold human insulins (Novolin and Humulin) and then RAAs. That would be a 3 minute commercial no one would pay attention to and likely wouldn't be allowed by FDA. Average Joes don't care about the chemical details of their pharmaceuticals. Afrezza should be marketed on the differences in it's efficacy (with existing data if FDA allows it or the backing of new trials), not some distinction that no one would pay attention to.
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Post by ktim on Apr 24, 2019 14:00:56 GMT -5
Mango, is it correct to say that intravenous human insulin has the same pk profile as afrezza? Obviously you can't use IV therapy outside of a hospital, but it should be mentioned if we're trying to be extremely acurate in comparing insulins. Human insulin, as well as RAA, would have same profile as Afrezza if given IV.
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Post by longliner on Apr 24, 2019 14:10:14 GMT -5
The longer Mannkind survives, the louder it's critics become. I don't believe I have ever (since 2008) seen the level of bashing on all forums that I have seen today! I guess MC is getting under someones skin.
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