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Post by derek2 on Apr 11, 2017 8:03:18 GMT -5
They should be. I have a bearish reputation, and message boards are full of charlatans. People need a good BS detector and I respect when they use it. I'm always prepared to back up what I say, or if I'm proven wrong, to publicly admit an error and change my position. Why keep being wrong?
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Post by slapshot on Apr 11, 2017 8:07:24 GMT -5
The fact that MNKD only asked for the label that the data justifies, in no way proves what the possible limits are. Just because they only tested 'end use' storage at room temperature for 30 days does not mean that we would see degradation at day 31, or 131...
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Post by Deleted on Apr 11, 2017 8:08:56 GMT -5
derek2 "Many people won't care, since the drug is approved, but it shows that those stating that Afrezza does not require refrigeration should take heed of the proof that there is degradation at room temp over longer time periods." "Personally, as a fan of data, not supposition" Proof requires data as you stated: where is the data to back up your claim insulin breaks down at room temperature??? A diamond will eventually become graphite, but not in one's lifetime. So get real and stop your FUD.
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Post by matt on Apr 11, 2017 8:56:31 GMT -5
where is the data to back up your claim insulin breaks down at room temperature??? Essentially all human proteins degrade over time, insulin included, and that is why all insulin products on the market have an expiration date. The data you are looking for is in the stability study results that each manufacturer has submitted to FDA as part of the CMC submission when the drug is approved. Every insulin manufacturer recommends refrigerated storage at 5 degrees Celsius for long-term storage, and several have documented potency degradation when stored at 10 degrees Celsius for as little as 14 days. Running a temperature segregated warehouse and temperature controlled distribution system is a pain in the backside, and is expensive to manage. No manufacturer signs up for anything other than room temperature storage (defined for the medical industry as 6 to 30 degrees C) unless their stability tests prove that it is needed.
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Post by derek2 on Apr 11, 2017 9:04:20 GMT -5
derek2 "Many people won't care, since the drug is approved, but it shows that those stating that Afrezza does not require refrigeration should take heed of the proof that there is degradation at room temp over longer time periods." "Personally, as a fan of data, not supposition" Proof requires data as you stated: where is the data to back up your claim insulin breaks down at room temperature??? A diamond will eventually become graphite, but not in one's lifetime. So get real and stop your FUD. Well, the results in table 8 and 9 are redacted, so all we know is that the results supported MNKD's proposed storage instructions, and that the FDA agreed. Insulin does indeed break down at room temperature. That's the question you're asking. Actually, it's "The Question" as in "Begging the question" with the question being "What proof do you have to show for your assertion?" When I show the proof below, you'll state "yes, but MNKD states that Technosphere stabilizes the insulin." See how the time wasting game works? Just string me along one objection at a time. (That objection, BTW, is answered by the fact that MNKD recommends 10-day room temperature excursions as opposed to 30 - 60 days recommended by competing mealtime insulins. It's in their best interest to show that they are as stable or more stable than competitors) icmr.nic.in/ijmr/2009/august/0910.pdf
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Post by slapshot on Apr 11, 2017 9:17:41 GMT -5
where is the data to back up your claim insulin breaks down at room temperature??? Essentially all human proteins degrade over time, insulin included, and that is why all insulin products on the market have an expiration date. The data you are looking for is in the stability study results that each manufacturer has submitted to FDA as part of the CMC submission when the drug is approved. Every insulin manufacturer recommends refrigerated storage at 5 degrees Celsius for long-term storage, and several have documented potency degradation when stored at 10 degrees Celsius for as little as 14 days. Running a temperature segregated warehouse and temperature controlled distribution system is a pain in the backside, and is expensive to manage. No manufacturer signs up for anything other than room temperature storage (defined for the medical industry as 6 to 30 degrees C) unless their stability tests prove that it is needed. No doubt, but even so, based on the report we still don't know how many days Afrezza can be stored at room temperature (or higher temps) without noticeable degradation. The point of the discussion, i believe, was that Derek felt the reports disproved Al Mann's statement that "Afrezza does not need refrigeraton" and that management didn't run stability studies to prove his statement. Both of which are not proved or disproved by the report.... since stability studies were only performed under refrigeration.
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Post by Deleted on Apr 11, 2017 9:19:13 GMT -5
"Storage at 32 and 37ºC showed 14-18 per cent decrease in potency of insulin in both the formulations on 28th day for all the three brands."
Do you have data that insulin combined with FDKP breaks down to any appreciable extent at room temperature? Any data to back up the claim FDKP is NOT inert?
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Post by derek2 on Apr 11, 2017 9:55:40 GMT -5
Essentially all human proteins degrade over time, insulin included, and that is why all insulin products on the market have an expiration date. The data you are looking for is in the stability study results that each manufacturer has submitted to FDA as part of the CMC submission when the drug is approved. Every insulin manufacturer recommends refrigerated storage at 5 degrees Celsius for long-term storage, and several have documented potency degradation when stored at 10 degrees Celsius for as little as 14 days. Running a temperature segregated warehouse and temperature controlled distribution system is a pain in the backside, and is expensive to manage. No manufacturer signs up for anything other than room temperature storage (defined for the medical industry as 6 to 30 degrees C) unless their stability tests prove that it is needed. No doubt, but even so, based on the report we still don't know how many days Afrezza can be stored at room temperature (or higher temps) without noticeable degradation. The point of the discussion, i believe, was that Derek felt the reports disproved Al Mann's statement that "Afrezza does not need refrigeraton" and that management didn't run stability studies to prove his statement. Both of which are not proved or disproved by the report.... since stability studies were only performed under refrigeration. You didn't read my reply to you or didn't read it completely. Stability tests were indeed run at room temperature as well as refrigerated. Sample for the extension or end use study: Stored at 25 degrees Celsius (74 deg F) for up to 30 days Stored at 35 degrees Celsius (90 deg F) for up to 10 days
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Post by derek2 on Apr 11, 2017 11:00:25 GMT -5
"Storage at 32 and 37ºC showed 14-18 per cent decrease in potency of insulin in both the formulations on 28th day for all the three brands." Do you have data that insulin combined with FDKP breaks down to any appreciable extent at room temperature? Any data to back up the claim FDKP is NOT inert? To quote myself: However - I've already stated that the data in the tables for the room temperature stability tests is redacted, so you know that already. I've also stated that it acted as the basis for MNKD suggesting 10 days at room temperature and for the FDA agreeing. That's obvious. I have no idea whether MNKD left money on the table as far as Afrezza stability goes, but they suggested and then signed off on what is now in the label. The question - since MNKD are the ones who suggested the 15 day (then 10 day) room temp excursions - is this: Why did they suggest a time at room temperature that is 1/3 to 1/2 of their competitors? It does not lend credence to Afrezza being extra stable at room temperature. But, given that the detailed data are redacted, nobody around here can say for sure. Regarding FDPK: Yes - when injected at high (or not so high depending on the animal) it causes fetal malformations and other problems. Of course, we're not injecting FDKP with Afrezza, but that wan't your question. Suggested time wasting follow-up: "But those studies were for injected FDKP. We're inhaling it and MNKD says it gets cleared from the system quickly."
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Post by peppy on Apr 11, 2017 11:08:22 GMT -5
"Storage at 32 and 37ºC showed 14-18 per cent decrease in potency of insulin in both the formulations on 28th day for all the three brands." Do you have data that insulin combined with FDKP breaks down to any appreciable extent at room temperature? Any data to back up the claim FDKP is NOT inert? To quote myself: However - I've already stated that the data in the tables for the room temperature stability tests is redacted, so you know that already. I've also stated that it acted as the basis for MNKD suggesting 10 days at room temperature and for the FDA agreeing. That's obvious. I have no idea whether MNKD left money on the table as far as Afrezza stability goes, but they suggested and then signed off on what is now in the label. The question - since MNKD are the ones who suggested the 15 day (then 10 day) room temp excursions - is this: Why did they suggest a time at room temperature that is 1/3 to 1/2 of their competitors? It does not lend credence to Afrezza being extra stable at room temperature. But, given that the detailed data are redacted, nobody around here can say for sure. Regarding FDPK: Yes - when injected at high (or not so high depending on the animal) it causes fetal malformations and other problems. Of course, we're not injecting FDKP with Afrezza, but that wan't your question. Suggested time wasting follow-up: "But those studies were for injected FDKP. We're inhaling it and MNKD says it gets cleared from the system quickly." let's cut through all the carp. You are a type two diabetic on medications. Be honest. With all you know,- if you are a non smoker, -if Afrezza was covered by Canadian medical insurance Would you choose, (your choice) to use afrezza to treat the type two you are now treating with other medication? I really would like to know.
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Post by mango on Apr 11, 2017 11:16:30 GMT -5
derek2 your silence is deafening! Well, I was asleep. My wife wishes I was silent when I sleep! Personally, as a fan of data, not supposition, I was excited to find this. The info is there, you just have to read. And hey, since the drug got approved, it's overwhelmingly positive info. An example: Some posters hang on Al Mann's statement that Afrezza does not need refrigeration. Others accuse management if not doing their job by running a stability trial. Well, turns out both extremes are wrong. The Chemistry Review shows that MNKD ran stability tests over a 3-year period, and it was MNKD that proposed the 18 months refrigerated and 10 days at room temperature storage, and that the FDA agreed. (Chemistry Review, P 47, Other Reviews, page 22-24) So the reason that I find this fascinating is that it shows that all parties acted rationally and professionally and came to an agreement. No evil FDA, no stupid MNKD. Many people won't care, since the drug is approved, but it shows that those stating that Afrezza does not require refrigeration should take heed of the proof that there is degradation at room temp over longer time periods. Who showed that? MNKD. It's real-world data that can help patients get the best result.EDIT: EDIT: The fact that a 3-year stability study was already performed also acts as a signal that a change in storage instructions is probably not part of the requested label change. It's not like MNKD was bullied into this - they recommended it after 3 years of data collection. This gives you more information as an investor. I mean, you might still think that MNKD could have requested the storage instruction change, but you have more real-world data to base your opinion on, instead of just "it would be great if" positing. Now, what it says about how in-the-loop Al was when he was claiming "no refrigeration" since 2010 is another thing. Maybe he didn't talk to the chemists. Re: the pregnant women warning: The Medical review shows pregnant rabbits & mice having fetal malformations at VERY HIGH concentrations of FDKP. Concentrations that would never be seen in real life, but it acted as a rational basis for MNKD and the FDA to determine toxicity baselines and set a margin of safety. You know what could be seen in real life? A pregnant mother taking 2 times the recommended starting dose of Lantus and her child developing Down Syndrome. Do you reckon that dose is realistic? I do. Pregnant rabbits and rats were given up to 100 mg/kg/day of FDKP. The adverse results group was illustrated with only by literally drowning the test subjects in those kind of high daily doses on top of also administering large amounts of Afrezza. However, as you can see via the data, LANTUS was given to rats and rabbits with a dose of only 0.36 mg/kg/day and 0.072 mg/kg/day, respectively. Amazingly, five rabbits, which were only given 2 times the recommended daily starting dose—developed Ventriculomegaly. They considered that a high-dose—what were MannKind's doses? Heroic doses? I would venture to say that even the regular starting dose of Lantus would produce similar effects. Do you have the data that proves it does not? Which study was more rigorous and unbiased?. Which company doesn't feel the need to assert to name dropping in literally every single adverse event study? You know what I mean, that infamous— Like how the makers of Lantus chose to use that cop out in their's: Not only did those rabbits develop Down Syndrome from receiving a mere 2 times the recommended starting dose of Lantus, but an excessive amount of female mice died from receiving only 5 times the recommended starting dose of Lantus while the male rats and mice developed histiocytomas. Per the data—you should be concerned with every insulin except Afrezza. Per the data.
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Post by mnkdfann on Apr 11, 2017 11:42:22 GMT -5
They should be. I have a bearish reputation, and message boards are full of charlatans. People need a good BS detector and I respect when they use it. I'm always prepared to back up what I say, or if I'm proven wrong, to publicly admit an error and change my position. Why keep being wrong? Derek, I love your photo avatar, but perhaps consider changing it to something like: Just kidding.
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Post by derek2 on Apr 11, 2017 12:04:55 GMT -5
To quote myself: However - I've already stated that the data in the tables for the room temperature stability tests is redacted, so you know that already. I've also stated that it acted as the basis for MNKD suggesting 10 days at room temperature and for the FDA agreeing. That's obvious. I have no idea whether MNKD left money on the table as far as Afrezza stability goes, but they suggested and then signed off on what is now in the label. The question - since MNKD are the ones who suggested the 15 day (then 10 day) room temp excursions - is this: Why did they suggest a time at room temperature that is 1/3 to 1/2 of their competitors? It does not lend credence to Afrezza being extra stable at room temperature. But, given that the detailed data are redacted, nobody around here can say for sure. Regarding FDPK: Yes - when injected at high (or not so high depending on the animal) it causes fetal malformations and other problems. Of course, we're not injecting FDKP with Afrezza, but that wan't your question. Suggested time wasting follow-up: "But those studies were for injected FDKP. We're inhaling it and MNKD says it gets cleared from the system quickly." let's cut through all the carp. You are a type two diabetic on medications. Be honest. With all you know,- if you are a non smoker, -if Afrezza was covered by Canadian medical insurance Would you choose, (your choice) to use afrezza to treat the type two you are now treating with other medication? I really would like to know.
You know what the most ridiculous thing about this is? You think I'm bashing Afrezza. I have been consistent in my view: 1. Afrezza is a slightly milder insulin than SC and costs around the same. Proven in clinical trials. 2. Management has been arrogant, self-enriching, foot-dragging, and may well deny me the chance to try Afrezza. 3. Related to #2: Al Mann was a salesman, to the point of sometimes going to far in his claims. 4. I take about 50 IU of SC at meals and 70IU of basal at supper time. It can burn like a bitch. Of course I'd give it a try, but I suspect that given my dose, it wouldn't be sufficient, but who knows? I may be one of the folks it works great for. 5. There's nothing magical about Afrezza, and I push back on those who ignore 6000 people in clinical trials and instead cherry pick from about a dozen people active on social media, ignoring the thousands that have discontinued for various reasons. Kind of like going through Google results until you find the one that agrees with you at result #36. *Of course, if somebody thinks that Afrezza has no side effects, when I talk about side effects, they think I'm bashing, even though their view is what's distorted. *If somebody thinks that retail short sellers inflate the share count by 20M shares (post split), when I talk about dilution increasing the share count by 60M shares, they think I'm bashing. *If somebody thinks that Afrezza is the most effective diabetes treatment ever, when I talk about Mike C stating that efficacy is one of the top 2 reasons for lack of Rx renewals, some how I'm bashing. *When I state that Google, Dexcom, Novo, Microsoft, are not about to buy out MNKD somehow I'm wrong, and yet no apologies to the board by self-purported insiders when they are again and again shown to be spouting self-serving folderol. *When I show that MNKD has not only not tested on children (other than inhaler handling - no insulin)but asked (and received permission) to put pediatric testing off by a decade (2021 completion instead of the 2011 NDA), somehow it's me that's against children. MNKD would be just as happy for those with poor reading skills to think that the FDA begged _them_ to test on children as opposed to MNKD asking not to have to test on (nor sell to) children. To reiterate: 1. Afrezza is an approved treatment option for diabetics. Some people find that it works well. 37% did in the trials, and it looks like about the same number do in the commercial market. Yay for them. 2. Of course I'd try a titration pack to see if it worked. I've hung around this long! 3. For me, it's not Afrezza, but it _is_ magical thinking about Afrezza that I'm against. 4. And yeah, it _is_ management.
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Post by derek2 on Apr 11, 2017 12:19:05 GMT -5
They should be. I have a bearish reputation, and message boards are full of charlatans. People need a good BS detector and I respect when they use it. I'm always prepared to back up what I say, or if I'm proven wrong, to publicly admit an error and change my position. Why keep being wrong? Derek, I love your photo avatar, but perhaps consider changing it to something like: Just kidding. Updated, although maybe this would be more appropriate, social skills wise:
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Post by kbrion77 on Apr 11, 2017 12:27:41 GMT -5
let's cut through all the carp. You are a type two diabetic on medications. Be honest. With all you know,- if you are a non smoker, -if Afrezza was covered by Canadian medical insurance Would you choose, (your choice) to use afrezza to treat the type two you are now treating with other medication? I really would like to know.
You know what the most ridiculous thing about this is? You think I'm bashing Afrezza. I have been consistent in my view: 1. Afrezza is a slightly milder insulin than SC and costs around the same. Proven in clinical trials. 2. Management has been arrogant, self-enriching, foot-dragging, and may well deny me the chance to try Afrezza. 3. Related to #2: Al Mann was a salesman, to the point of sometimes going to far in his claims. 4. I take about 50 IU of SC at meals and 70IU of basal at supper time. It can burn like a bitch. Of course I'd give it a try, but I suspect that given my dose, it wouldn't be sufficient, but who knows? I may be one of the folks it works great for. 5. There's nothing magical about Afrezza, and I push back on those who ignore 6000 people in clinical trials and instead cherry pick from about a dozen people active on social media, ignoring the thousands that have discontinued for various reasons. Kind of like going through Google results until you find the one that agrees with you at result #36. *Of course, if somebody thinks that Afrezza has no side effects, when I talk about side effects, they think I'm bashing, even though their view is what's distorted. *If somebody thinks that retail short sellers inflate the share count by 20M shares (post split), when I talk about dilution increasing the share count by 60M shares, they think I'm bashing. *If somebody thinks that Afrezza is the most effective diabetes treatment ever, when I talk about Mike C stating that efficacy is one of the top 2 reasons for lack of Rx renewals, some how I'm bashing. *When I state that Google, Dexcom, Novo, Microsoft, are not about to buy out MNKD somehow I'm wrong, and yet no apologies to the board by self-purported insiders when they are again and again shown to be spouting self-serving folderol. *When I show that MNKD has not only not tested on children (other than inhaler handling - no insulin)but asked (and received permission) to put pediatric testing off by a decade (2021 completion instead of the 2011 NDA), somehow it's me that's against children. MNKD would be just as happy for those with poor reading skills to think that the FDA begged _them_ to test on children as opposed to MNKD asking not to have to test on (nor sell to) children. To reiterate: 1. Afrezza is an approved treatment option for diabetics. Some people find that it works well. 37% did in the trials, and it looks like about the same number do in the commercial market. Yay for them.2. Of course I'd try a titration pack to see if it worked. I've hung around this long! 3. For me, it's not Afrezza, but it _is_ magical thinking about Afrezza that I'm against. 4. And yeah, it _is_ management. Unfortunately people around here are really losing track of this statement. Afrezza is an OPTION and hopefully an option that helps PWDs in their day to day struggle. It is not the standard care and it doesn't work for everybody. It's along the same lines as when someone used to post on a social media outlet that it doesn't work for them and next thing you know numerous people were all over them for bashing, bizarre.
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