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Post by audiomr on Aug 17, 2016 12:19:11 GMT -5
The FDA however does not care about science, only about massive and expensive studies so I have no doubt they have made it prohibitively expensive for MNKD to prove that Afrezza is safe outside of the fridge (at least for a few weeks - maybe months). That is an uncalled for slander against the reputation of a the world's best drug regulatory agency. To say that you cannot have a reasoned scientific discussion with the FDA is simply not true, and I have sat in the office of more stubborn and bone-headed regulators around the world than I would like to think about. FDA is the best of them all, bar none. The people that work there cannot be compared to the stereotypical bureaucrat at the DMV; these are people with advanced degrees (many of them multiple advanced degrees) and they have spouses, children, and extended families affected by disease just like everybody else. Most are extremely contentious. FDA approves what the sponsor submits, and that is a molecule in a particular form. If the sponsor can show that the molecule is unaffected by temperature, humidity or other factors then the storage conditions on the label reflect that. Stability testing is a standard requirement for all drugs, and the tests are not particularly expensive to perform. In most cases it consists of taking a samples of a drug and putting it on a shelf in controlled conditions and periodically testing one of the samples to show the drug has not changed. Physical, chemical, biological, and microbiological tests, including particular attributes of the dosage form. In the case of Afrezza, that means that the drug is molecularly stable and atomizes as intended for delivery into the lung. It is not unreasonable to require a manufacturer to show that their drug works under various real world conditions. Why are there rules on stability testing? Because of the numerous examples of drugs that are ineffective for treating patients when the drug is unstable. FDA has a legal obligation to insure that all drugs sold in this country are both safe and effective, and it is Mannkind's responsibility to produce the data to show that Afrezza meets that standard. If Mannkind had good stability data at room temperature and uncontrolled humidity, they would be able to say so. Either they elected to take a short cut and didn't do the testing, or they did the testing and the results showed that Afrezza is not stable. Either way, it is up to Mannkind to address the issue. Well said. |
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Post by babaoriley on Aug 17, 2016 18:31:04 GMT -5
Some have argued that 'fast' acting insulin analogs like lispro (humalog) and aspart (novolog) and glulisine (apidra) are delivered in monomers so Afrezza can not make the claim to be unique in this respect. This is not the complete truth: 1) Afrezza is true regular human insulin (RHI). It is identical to the insulin native to the human body. All the analogs have changes in their amino acid sequence (let's call them mutations) in order to give them a better time-action profile. Because of the mutations, they are not called 'insulin', but rather 'insulin analogs'. In other words, while there might be 'monomeric insulin analogs', Afrezza is the only 'monomeric insulin'. 2) Lispro and Aspart might not self-assembly into hexamers, but the producers still add zinc and excipients that ENCOURAGE formation of hexamers, to improve stability and prevent fibrillization. So delivery is still in large part hexameric which is reversed upon injection as the excipients diffuse and hexamers disassociate faster then injected RHI. In other words, monomers are only a small part of lispro and aspart upon injection. 3) Apidra is indeed an hexamer-free (and zinc free) analog that has only monomers and dimers. The mutations seem more significant to me. While apidra still self-assembles into dimers (helping stability in absense of hexamers), it seems there is still a large amount of the mutated insulin in monomeric form. This would explain why it is somewhat faster then lispro & aspart. This is a very unpopular analog, but that might be because it is marketed by Sanofi - we do have some anecdotal evidence after all. The only real downside as compared to lispro & aspart that I've found is that it degenerates faster then the others (esp when not kept very cold). Note that the main reason for hexamers is stability of the solution (and prevention of fibril formation). In Afrezza this problem is solved by suspending monomers in technosphere (fdkp) particles. As to what is more important: being monomeric or being inhaled; look no further then this comparison of Exubera vs analogs vs RHI: www.ncbi.nlm.nih.gov/pubmed/15855570In this study it was shown that (hexameric) Exubera was in the blood for longer then Lispro, even though its time-to-action was faster. This was due entirely to its hexameric state. So if this delay is due to hexamers, but a (partially?) monomeric injected analog (Apidra) is also in the blood for very long, is it the injection or the hexamers that make other insulins linger? Both. If there are either hexamers or the insulin or analog is injected, it will add hours to the time-action profile. These times are mostly overlapping, which explains why a monomeric injected insulin is not twice as fast as a hexameric injected insulin, and why hexameric inhaled is similar to monomeric injected. Bob, you stay away more than a year, and then you give us the above. Tell us something we don't already know! Good to see your handle back on here! Matt: "The people that work there (the FDA) cannot be compared to the stereotypical bureaucrat at the DMV." I suppose that's "called-for" slander aimed at the DMV? Watch out, they may take your license away.  Whether others agree with you or not about the brilliance and purity of the FDA, it sure as heck looks as if they were scared to death by Marty Shkreli. And if Marty was right, then maybe they aren't always so brilliant. There's corruption everywhere, is it less at the FDA than other places (and certainly not limiting this to government)? Maybe and I'll even give you probably. |
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Post by silentbob on Sept 5, 2016 11:40:46 GMT -5
The FDA however does not care about science, only about massive and expensive studies so I have no doubt they have made it prohibitively expensive for MNKD to prove that Afrezza is safe outside of the fridge (at least for a few weeks - maybe months). That is an uncalled for slander against the reputation of a the world's best drug regulatory agency. To say that you cannot have a reasoned scientific discussion with the FDA is simply not true, and I have sat in the office of more stubborn and bone-headed regulators around the world than I would like to think about. I disagree. It might very well be the best in the world, but it certainly isn't as good as it should be. You apparently weren't here when the FDA forced MNKD to run trials where Afrezza had to be used exactly like RAA was, in spite of the significantly different action profile. That's right, the patients were not allowed to decide their dose of Afrezza, the FDA knows better. The FDA reasoning was to prove equivalency at a specific dose conversion, but these drugs are do different that this requirement is nonsensical. Patients should have been able to do as they would have in the real world. If they use more Afrezza, then that should have been on the label instead. You also obviously haven't followed the ADCOM where the FDA speakers demonstrated their ignorence of diabetes several times, in one case even prompting one of the experts to answer "you would be killing my patients". You also didn't consider how much more positive the experts were then the FDA themselves. And since the FDA almost had to approve because of the unanimous positive vote of the ADCOM experts, they gave it a much more restrictive label then the experts indicated. The FDA in general might be professional. But in this case, it was extremely unprofessional. |
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Post by sweedee79 on Sept 5, 2016 12:32:39 GMT -5
This [Apidra] is a very unpopular analog, but that might be because it is marketed by Sanofi - we do have some anecdotal evidence after all. The only real downside as compared to lispro & aspart that I've found is that it degenerates faster then the others (esp when not kept very cold). It's not that Apidra is unpopular but rather that so few insurers cover it. I would swap to it in a heartbeat but I have yet to have an insurer who covers it. this is correct... I checked into it for my dad when his insurance took Afrezza off of its formulary.... it seems that insurance companies seek to provide coverage for only novolog or Humalog.. Medicare Part D plans are the worst for limiting coverage.. Our poor seniors.. Many of the newer drugs , insulin etc . face lack of coverage.. this seems to be the trend and IMO will continue to get worse as our health care system continues to have problems. Its all about the money. The recent price increases of both Novolog and Humalog will help our cause.
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Post by avichen on Sept 5, 2016 13:21:03 GMT -5
It's not that Apidra is unpopular but rather that so few insurers cover it. I would swap to it in a heartbeat but I have yet to have an insurer who covers it. this is correct... I checked into it for my dad when his insurance took Afrezza off of its formulary.... it seems that insurance companies seek to provide coverage for only novolog or Humalog.. Medicare Part D plans are the worst for limiting coverage.. Our poor seniors.. Many of the newer drugs , insulin etc . face lack of coverage.. this seems to be the trend and IMO will continue to get worse as our health care system continues to have problems. Its all about the money. The recent price increases of both Novolog and Humalog will help our cause.
that sounds bad.  I'm not in US but seems like something is very wrong with the system. Those big pharma increases the price and the insurance company keep paying them, but for those small pharma providing new drugs, they never fully cover it. I wonder how much under table money involved... |
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Post by rockstarrick on Sept 5, 2016 13:33:55 GMT -5
Hi Derek, Thanks for your praise but I don't deserve it; all I do is google now and then. If you are 'Dereklinders' from the yahoo days I hold you in high regard as well. The reason why I feel the analog differentiation is important is that in humans a single amino acid change at any point can mean a massive difference. Yes the RAA may hit the insulin receptors, but that does not make them equal. They are different molecules. Some argue that there are unknowns dangers with Afrezza. I argue there are both serious known and unknown dangers with RAA. I can look for sources on the RAA mono/dime/hexameric solutions if you want... BTW, recombinant refers to the production method - both that of RHI and RAA. It was a good differentiator back in the days of pig insulin, but now insulin and analogs are both produced this way and so it no longer confers information. For that reason I feel it is a poor name for RHI, and I think this is also why the term 'regular' seems to be used more often these days. I am indeed the same Derek . I agree with you that recombinant human insulin is really human insulin, just not produced by a human. Probably safer as well, since it lacks other proteins / antigens / pathogens that you would get from extracting from humans (shudder) or from pigs. You have great taste in Guitars !! Is that yours ?? |
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Post by mnholdem on Sept 5, 2016 13:59:29 GMT -5
Is that a Wildkat?
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Post by derek2 on Sept 5, 2016 16:23:41 GMT -5
It is indeed a Wildkat. I re-wired it with lower capacitance wire, replaced the pots with CTS 500K and added a Varitone switch, and it makes me sound like I don't suck! (At least to my ears) Wildkats are a super value, in my opinion. (also, thanks rockstarrick for the compliment. It's much prettier than me!) |
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Post by rockstarrick on Sept 5, 2016 18:20:12 GMT -5
It is indeed a Wildkat. I re-wired it with lower capacitance wire, replaced the pots with CTS 500K and added a Varitone switch, and it makes me sound like I don't suck! (At least to my ears) Wildkats are a super value, in my opinion. (also, thanks rockstarrick for the compliment. It's much prettier than me!) A Guitar with a Bigsby !! I'll bet you are a great player, rookies usually steer clear of things like capacitors, Varitone switches, and especially Bigsbys. She's a Beauty. |
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Post by peppy on Sept 5, 2016 18:31:10 GMT -5
it was just a matter of time before the men started talking guitars.
weehaw.
Have fun.
Afrezza, technosphere insulin. Regular human insulin delivered as a monomer. Easy in, easy out. www.mannkindcorp.com/Collateral/Documents/English-US/Baughman%20poster%20100-LB%20FINAL%20X2.pdf Try it, you will like it. 
www.afrezza.com/ www.afrezza.com/find-a-doctor/ Afrezza is an ultra-rapid-acting insulin for people with type 1 and 2 diabetes, peaking in only 16-21 minutes versus about 60-90 minutes for current injected rapid-acting insulins such as Humalog and Novolog – that’s a big difference! Recent studies of Afrezza also showed that it lasts two-to-three hours less than other rapid-acting insulins. This is an important advantage for a mealtime insulin – fast-in, fast-out ensures the insulin covers food quickly, without lingering and causing delayed low blood sugar. - See more at: diatribe.org/drugdevice-name/afrezza#sthash.RxbDq3rk.dpuf
4 units afrezza equivalent to 3.1 units of lispro.
(Liane, I know you remember when I used to try and bury these marketing attempts off topic? Those were the days... )
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Post by mnholdem on Sept 5, 2016 19:53:05 GMT -5
it was just a matter of time before the men started talking guitars.
weehaw.
Have fun.
[In-post marketing section - clipped]
(Liane, I know you remember when I used to try and bury these marketing attempts off topic? Those were the days... )
I don't presume to speak for liane , but I'm curious. You post good stuff, peppy, so why you find it necessary to repeatedly put these Afrezza marketing blurbs into your posts? The practice is like hijacking a thread and can steer the conversation in a completely different (and often unrelated) direction. Even though the brief discussion of the guitar avatar was also a brief diversion from the theme of this thread as well, it doesn't happen with as much regularity, IMHO. 
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Post by peppy on Sept 5, 2016 20:38:15 GMT -5
it was just a matter of time before the men started talking guitars.
weehaw.
Have fun.
[In-post marketing section - clipped]
(Liane, I know you remember when I used to try and bury these marketing attempts off topic? Those were the days... )
I don't presume to speak for liane , but I'm curious. You post good stuff, peppy, so why you find it necessary to repeatedly put these Afrezza marketing blurbs into your posts? The practice is like hijacking a thread and can steer the conversation in a completely different (and often unrelated) direction. Even though the brief discussion of the guitar avatar was also a brief diversion from the theme of this thread as well, it doesn't happen with as much regularity, IMHO.
I know I am bad. The thread, Afrezza the only monomeric human insulin. Here is what I really think. I would print it, it being the fact Afrezza is a monomer. I would talk about it. I want to treat the customer as well as the physician like they have brains. I found how afrezza works fascinating. I say we fascinate the world. This video is fascinating. It does not mention monomer. Instead it refers to technosphere insulin. hcp.afrezza.com/how-afrezza-works/
I'll try and thread behave.
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Post by brotherm1 on Sept 6, 2016 6:57:37 GMT -5
it was just a matter of time before the men started talking guitars.
weehaw.
Have fun.
Afrezza, technosphere insulin. Regular human insulin delivered as a monomer. Easy in, easy out. www.mannkindcorp.com/Collateral/Documents/English-US/Baughman%20poster%20100-LB%20FINAL%20X2.pdf Try it, you will like it.
www.afrezza.com/ www.afrezza.com/find-a-doctor/ Afrezza is an ultra-rapid-acting insulin for people with type 1 and 2 diabetes, peaking in only 16-21 minutes versus about 60-90 minutes for current injected rapid-acting insulins such as Humalog and Novolog – that’s a big difference! Recent studies of Afrezza also showed that it lasts two-to-three hours less than other rapid-acting insulins. This is an important advantage for a mealtime insulin – fast-in, fast-out ensures the insulin covers food quickly, without lingering and causing delayed low blood sugar. - See more at: diatribe.org/drugdevice-name/afrezza#sthash.RxbDq3rk.dpuf
4 units afrezza equivalent to 3.1 units of lispro.
(Liane, I know you remember when I used to try and bury these marketing attempts off topic? Those were the days... )
[ "Afrezza is an ultra-rapid-acting insulin for people with type 1 and 2 diabetes, peaking in only 16-21 minutes versus about 60-90 minutes for current injected rapid-acting insulins such as Humalog and Novolog – that’s a big difference! Recent studies of Afrezza also showed that it lasts two-to-three hours less than other rapid-acting insulins. This is an important advantage for a mealtime insulin – fast-in, fast-out ensures the insulin covers food quickly, without lingering and causing delayed low blood sugar. - See more at: diatribe.org/drugdevice-name/afrezza#sthash.RxbDq3rk.dpuf[/p] 4 un"
Peppy - Is the above a quote from one of the links you supplied with it? If so, which one and perhaps where on the link is it located? |
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Post by peppy on Sept 6, 2016 7:28:21 GMT -5
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Whether others agree with you or not about the brilliance and purity of the FDA, it sure as heck looks as if they were scared to death by Marty Shkreli. And if Marty was right, then maybe they aren't always so brilliant. There's corruption everywhere, is it less at the FDA than other places (and certainly not limiting this to government)? Maybe and I'll even give you probably. 
I'm not in US but seems like something is very wrong with the system. Those big pharma increases the price and the insurance company keep paying them, but for those small pharma providing new drugs, they never fully cover it. I wonder how much under table money involved...
