|
Post by sayhey24 on Apr 3, 2017 20:06:31 GMT -5
I'm not quite sure what that means. Are you objecting to something I wrote? I would agree that the system is broken, although I would argue that it's dysfunctional rather than corrupt. The system is certainly Dysfunctional And The system is certainly corrupt!
Even a minimal amount of DD will enlighten one to realize that these are both facts! GLTA TRUE LONGS!! Aged said - "Right there you have the only evidence the medical profession cares about - clinical trial data. A doctor's personal experience is the only thing which will override it. You might not like it, but that's just the way it is, and right now the trial data says they have the same outcome. Want to change that? Run a trial to prove superiority, and currently the outcome of choice is HbA1c reduction although if you want to finance CGMs for the trial you could use time in range."I thought SNY already did the clamp studies and afrezza was hands-down the winner. I guess we will know in a few months how corrupt the FDA still is. With Peggy and her boss both gone I am hoping MNKD can get the label change approved which will end this label discussion.
|
|
|
Post by agedhippie on Apr 3, 2017 20:15:20 GMT -5
The system is certainly Dysfunctional And The system is certainly corrupt!
Even a minimal amount of DD will enlighten one to realize that these are both facts! GLTA TRUE LONGS!! Aged said - "Right there you have the only evidence the medical profession cares about - clinical trial data. A doctor's personal experience is the only thing which will override it. You might not like it, but that's just the way it is, and right now the trial data says they have the same outcome. Want to change that? Run a trial to prove superiority, and currently the outcome of choice is HbA1c reduction although if you want to finance CGMs for the trial you could use time in range."I thought SNY already did the clamp studies and afrezza was hands-down the winner. I guess we will know in a few months how corrupt the FDA still is. With Peggy and her boss both gone I am hoping MNKD can get the label change approved which will end this label discussion. Clamp test has nothing to do with time in range, it just shows the PD/PK. In turn PD/PK is irrelevant unless it improves the outcome which it did not show in the trial.
|
|
|
Post by sayhey24 on Apr 3, 2017 20:30:13 GMT -5
Aged said - "Right there you have the only evidence the medical profession cares about - clinical trial data. A doctor's personal experience is the only thing which will override it. You might not like it, but that's just the way it is, and right now the trial data says they have the same outcome. Want to change that? Run a trial to prove superiority, and currently the outcome of choice is HbA1c reduction although if you want to finance CGMs for the trial you could use time in range."I thought SNY already did the clamp studies and afrezza was hands-down the winner. I guess we will know in a few months how corrupt the FDA still is. With Peggy and her boss both gone I am hoping MNKD can get the label change approved which will end this label discussion. Clamp test has nothing to do with time in range, it just shows the PD/PK. In turn PD/PK is irrelevant unless it improves the outcome which it did not show in the trial. Wow - I clearly misunderstood Ray Urbansky then and the significant time in range improvement afrezza showed. I wonder why he is wasting his time doing the label change? Did he do some other test? I always assumed if you could bring someone back to baseline really fast and then let the pancreas for T2s or the basal dosing for T1s keep them in that 80-90 range you could get pretty darn good A1c results. For some reason I thought that was what a healthy pancreas did, got them back to 80-85 or there abouts.
|
|
|
Post by agedhippie on Apr 4, 2017 7:53:17 GMT -5
Clamp test has nothing to do with time in range, it just shows the PD/PK. In turn PD/PK is irrelevant unless it improves the outcome which it did not show in the trial. Wow - I clearly misunderstood Ray Urbansky then and the significant time in range improvement afrezza showed. I wonder why he is wasting his time doing the label change? Did he do some other test? I always assumed if you could bring someone back to baseline really fast and then let the pancreas for T2s or the basal dosing for T1s keep them in that 80-90 range you could get pretty darn good A1c results. For some reason I thought that was what a healthy pancreas did, got them back to 80-85 or there abouts. Obviously you did misunderstand The clamp trials were to establish variability in PK/PD, and to establish the variability with dose size. The group size was 30 or less people so it was tiny, but that is understandable considering the objectives. There were no other trials, Mannkind (and Sanofi before them) have only done FDA mandated trials and have done nothing for label improvement. Your problem is that while you might think that Afrezza should give better results (and I agree with you there) the trial data says that it doesn't, and trial data is what matters. Oh, Urbanski said last May that they were considering time in range trials, but nothing ever happened.
|
|
|
Post by peppy on Apr 4, 2017 14:34:23 GMT -5
Wow - I clearly misunderstood Ray Urbansky then and the significant time in range improvement afrezza showed. I wonder why he is wasting his time doing the label change? Did he do some other test? I always assumed if you could bring someone back to baseline really fast and then let the pancreas for T2s or the basal dosing for T1s keep them in that 80-90 range you could get pretty darn good A1c results. For some reason I thought that was what a healthy pancreas did, got them back to 80-85 or there abouts. Obviously you did misunderstand The clamp trials were to establish variability in PK/PD, and to establish the variability with dose size. The group size was 30 or less people so it was tiny, but that is understandable considering the objectives. There were no other trials, Mannkind (and Sanofi before them) have only done FDA mandated trials and have done nothing for label improvement. Your problem is that while you might think that Afrezza should give better results (and I agree with you there) the trial data says that it doesn't, and trial data is what matters. Oh, Urbanski said last May that they were considering time in range trials, but nothing ever happened. Aged, yes, clamp study mandated. After the approval study. Does that make the clamp study and it's results a phase 4 study. it was a study. plenty of after approval studies run with 30 people. The pk affects the label? the pk was known before, so a dose study. .... in comparison to lispro. I see what you are saying. What that study did however is give time of inset 12 to 15 mins for afrezza and time of duration of action compared to lispro. As part of the study, it happened to be in comparison to lispro. is it that comparison? could the study information that compares afrezza to lispro be used? For label improvement?
Onset of activity for TI occurred ca. 25-35 minutes earlier than for Lispro. TI duration of action is about 2 hours shorter than an equivalent dose of Lispro.
www.mannkindcorp.com/Collateral/Documents/English-US/Baughman%20poster%20100-LB%20FINAL%20X2.pdf
|
|
|
Post by dreamboatcruise on Apr 4, 2017 15:40:51 GMT -5
Obviously you did misunderstand The clamp trials were to establish variability in PK/PD, and to establish the variability with dose size. The group size was 30 or less people so it was tiny, but that is understandable considering the objectives. There were no other trials, Mannkind (and Sanofi before them) have only done FDA mandated trials and have done nothing for label improvement. Your problem is that while you might think that Afrezza should give better results (and I agree with you there) the trial data says that it doesn't, and trial data is what matters. Oh, Urbanski said last May that they were considering time in range trials, but nothing ever happened. Aged, yes, clamp study mandated. After the approval study. Does that make the clamp study and it's results a phase 4 study. it was a study. plenty of after approval studies run with 30 people. The pk affects the label? the pk was known before, so a dose study. .... in comparison to lispro. I see what you are saying. What that study did however is give time of inset 12 to 15 mins for afrezza and time of duration of action compared to lispro. As part of the study, it happened to be in comparison to lispro. is it that comparison? could the study information that compares afrezza to lispro be used? For label improvement?
Onset of activity for TI occurred ca. 25-35 minutes earlier than for Lispro. TI duration of action is about 2 hours shorter than an equivalent dose of Lispro.
www.mannkindcorp.com/Collateral/Documents/English-US/Baughman%20poster%20100-LB%20FINAL%20X2.pdf
The prescribing info used from day one has the PD comparison chart with Afrezza curve vs Lispro curve (section 12.2). That doesn't seem to have excited doctors. What label improvement may now be possible is still up for speculation. Does the additional clamp study perhaps combined with the simulated patients give room to change the dosing instructions? I think very safe to say that they yet have no ammo to get any mention of superior A1C or time in range. Those would require additional trials.
|
|
|
Post by mnholdem on Apr 4, 2017 16:09:29 GMT -5
Take a step back and ask yourselves, "Why did MannKind develop the INsulin/OUTsulin campaign"? The answer is because the post-market trial did provide the necessary data for MannKind to apply for a new FDA re-classification of Ultra-Fast Acting insulin for Afrezza. It's all tied together. The FDA has already approved use of the new data for marketing purposes. The animated characters reinforce the message. What is needed now is a major medical journal publication that explains why the faster onset is so vitally important for the treatment of diabetes mellitus, especially in its early stages.
|
|
|
Post by agedhippie on Apr 4, 2017 16:18:46 GMT -5
Dreamboat put it well. Those clamp tests were about evaluating consistency rather than efficiency. The clamp test was to confirm that the PD chart included in the prescribing information was repeatable. As such I am not sure you could change the dosing instructions although that it is not to say you couldn't try (what is there to lose?)
The problem remains the non-superiority. Without that the clamp test are not going to change any minds because what matters is the result and not how you get there.
|
|
|
Post by agedhippie on Apr 4, 2017 16:21:14 GMT -5
Take a step back and ask yourselves, "Why did MannKind develop the INsulin/OUTsulin campaign"? The answer is because the post-market trial did provide the necessary data for MannKind to apply for a new FDA re-classification of Ultra-Fast Acting insulin for Afrezza. It's all tied together. The FDA has already approved use of the new data for marketing purposes. The animated characters reinforce the message. What is needed now is a major medical journal publication that explains why the faster onset is so vitally important for the treatment of diabetes mellitus, especially in its early stages. The problem is that a major journal will not publish that unless it can be derived from trial data which I am not sure it can. Oddly Novo Nordisk may be the best hope here because they have to prove that exact point to sell their new insulin.
|
|
|
Post by sayhey24 on Apr 4, 2017 20:51:05 GMT -5
Take a step back and ask yourselves, "Why did MannKind develop the INsulin/OUTsulin campaign"? The answer is because the post-market trial did provide the necessary data for MannKind to apply for a new FDA re-classification of Ultra-Fast Acting insulin for Afrezza. It's all tied together. The FDA has already approved use of the new data for marketing purposes. The animated characters reinforce the message. What is needed now is a major medical journal publication that explains why the faster onset is so vitally important for the treatment of diabetes mellitus, especially in its early stages. The problem is that a major journal will not publish that unless it can be derived from trial data which I am not sure it can. Oddly Novo Nordisk may be the best hope here because they have to prove that exact point to sell their new insulin. Now that the afrezza dosing approach is well understood, do you really think an analog can beat natural monomer insulin? I suspect they would need to go head to head against afrezza if Mike and Ray are doing their jobs. I doubt Novo will be able to show non-inferiority with proper afrezza dosing.
|
|
|
Post by agedhippie on Apr 4, 2017 22:22:43 GMT -5
The problem is that a major journal will not publish that unless it can be derived from trial data which I am not sure it can. Oddly Novo Nordisk may be the best hope here because they have to prove that exact point to sell their new insulin. Now that the afrezza dosing approach is well understood, do you really think an analog can beat natural monomer insulin? I suspect they would need to go head to head against afrezza if Mike and Ray are doing their jobs. I doubt Novo will be able to show non-inferiority with proper afrezza dosing. Novo Nordisk will do their superiority trial against Novolog, not against Afrezza. If Mannkind want to prove superiority they have to fund and run their own trial because Novo Nordisk won't pay for it! If Mannkind don't do the superiority trial then Novo Nordisk will have the only ultra rapid insulin that is superior to RAA.
|
|
|
Post by mnholdem on Apr 5, 2017 15:44:50 GMT -5
Now that the afrezza dosing approach is well understood, do you really think an analog can beat natural monomer insulin? I suspect they would need to go head to head against afrezza if Mike and Ray are doing their jobs. I doubt Novo will be able to show non-inferiority with proper afrezza dosing. Novo Nordisk will do their superiority trial against Novolog, not against Afrezza. If Mannkind want to prove superiority they have to fund and run their own trial because Novo Nordisk won't pay for it! If Mannkind don't do the superiority trial then Novo Nordisk will have the only ultra rapid insulin that is superior to RAA. Afrezza can ride on the coattails of Novo's multi $million trial data, assuming anyone in management has any sense. Ultra-rapid is a new class of insulin. If the FDA creates a new classification for Novo and MannKind, it's a new ballgame. Novo's trials will prove to the medical community why faster is better (sorry, ladies, but it's true ) and Afrezza will likely benefit from Novo's data the superiority of Ultra-Rapid PK/PD. MannKind may benefit because it already has the trial data to substantiate that Afrezza has an even faster onset than Novo's URAA. Mango go did an admirable job of explaining how diabetes KOLs make $millions, paid by BPs to publish papers worthy of major madical journals, although I don't fully agree with m that these PhDs are all corrupt. Pharmaceutical companies pay these academics primarily for their time required to research and publish papers. Frankly, MannKind also needs to pony up $$$ if they want viable research publications detailing the medical advantages of an Ultra-Fast insulin like Afrezza. I'm not sure they can afford it, but it's critical that they find a way to do so, IMO, and ASAP.
|
|