|
Post by mnholdem on Feb 21, 2017 9:07:09 GMT -5
Someone wrote about the dichotomy between a non-inferiority trial and their fantastic experience with Afrezza just about two years ago. They asked the question why does a non-inferior product work so well for them? The trial said Afrezza was non-inferior and their statement proves that is true for them. The next step is to have a trial to prove superiority. agedhippie,
I hope that the next step is for the FDA to reclassify Afrezza as a First-in-Class ultra-rapid/ultra-fast acting insulin. However, regarding your promoting a trial to demonstrate Afrezza's superiority to other insulin, it is entirely possible that MannKind's Chief Medical Officer (Dr. Urbanski) can demonstrate superiority using the pediatric trial, depending upon how the protocols are established.
Successfully meeting those endpoints would provide the "results" that you stated would convince the medical community and, regardless of anyone's viewpoint on mango's argument of a corrupt medical community, meeting superiority endpoints in a pediatric trial would make it very difficult for diabetes academics and/or KOLs to exclude Afrezza from any future discussions related to diabetes Standards of Care.
Urbanski must make sure that the primary and secondary endpoints are established in a way that, if Afrezza does NOT meet endpoints that establish superiority, the trial will still determine that it is safe and effective for pediatric treatment.
|
|
|
Post by saxcmann on Feb 21, 2017 9:08:59 GMT -5
Someone wrote about the dichotomy between a non-inferiority trial and their fantastic experience with Afrezza just about two years ago. They asked the question why does a non-inferior product work so well for them? The trial said Afrezza was non-inferior and their statement proves that is true for them. The next step is to have a trial to prove superiority. MNKD was forced to move forward with 171/175 trials to get fda approval. It's like having a Ferrari (afrezza) and make the driver stay in 2nd gear thru the race track!
|
|
|
Post by agedhippie on Feb 21, 2017 9:17:04 GMT -5
It doesn't matter how it works, what matters is the trial data and that data brackets RAA with Afrezza. This is really simple, they cannot ignore trial data. That's it - end of story. It DOES matter how it works... of course we all know we need trial data .. Mango brings up some interesting and valid points .. Things only change when someone begins to complain .. It appears to me that there are some conflicts of interest by the very people who set the standard of care for treatment of diabetes in this country .. Not sure what the answers are.. but it certainly merits discussion .. and I for one thank Mango for the time he spent bringing this to our attention... I used to work in academia in my now distant past and my disclosures would have looked similar to theirs. The reason is grant funding. Someone has to support research costs and government only covers a fraction of that cost so if we want research then the private sector is where that balance has to come from. That funding is attached to somebody and appears against their name in disclosures. The end result is that any doctor of consequence who also does research (and almost all do) will have disclosures - for this reason this is never going to change. You could raise it as an ethics issue but I suspect all you will get is confused expressions because nobody sees it as such.
|
|
|
Post by agedhippie on Feb 21, 2017 9:27:58 GMT -5
The trial said Afrezza was non-inferior and their statement proves that is true for them. The next step is to have a trial to prove superiority. agedhippie,
I hope that the next step is for the FDA to reclassify Afrezza as a First-in-Class ultra-rapid/ultra-fast acting insulin. However, regarding your promoting a trial to demonstrate Afrezza's superiority to other insulin, it is entirely possible that MannKind's Chief Medical Officer (Dr. Urbanski) can demonstrate superiority using the pediatric trial, depending upon how the protocols are established.
Successfully meeting those endpoints would provide the "results" that you stated would convince the medical community and, regardless of anyone's viewpoint on mango's argument of a corrupt medical community, meeting superiority endpoints in a pediatric trial would make it very difficult for diabetes academics and/or KOLs to exclude Afrezza from any future discussions related to diabetes Standards of Care.
Urbanski must make sure that the primary and secondary endpoints are established in a way that, if Afrezza does NOT meet endpoints that establish superiority, the trial will still determine that it is safe and effective for pediatric treatment.
Strictly pediatric trials would not prove superiority for adults since they are separate populations, however in the real world that would work and doctors would run with it I think. Getting Afrezza into a different class from RAA is critical. On their own I doubt Mannkind can do this however Novo Nordisk want to create an ultra-rapid class for the same reason (to distinguish FiAsp from other RAA) and will do the heavy lifting there. Once that is achieved then the Standard of Care can reference the class with guidance. I agree that it is critical for Mannkind not to drop the ball over the pediatric trials as (1) this should be available to kids, and (2) a fail for pediatrics would be the kiss of death for adoption.
|
|
|
Post by agedhippie on Feb 21, 2017 9:30:20 GMT -5
The trial said Afrezza was non-inferior and their statement proves that is true for them. The next step is to have a trial to prove superiority. MNKD was forced to move forward with 171/175 trials to get fda approval. It's like having a Ferrari (afrezza) and make the driver stay in 2nd gear thru the race track! We may never know but my gut feeling is that Mannkind played it safe with those trials and devised a protocol that they knew would pass rather than design a more aggressive protocol and risk failure.
|
|
|
Post by peppy on Feb 21, 2017 10:06:38 GMT -5
I think it took the continuous glucose monitors to really learn how to dose. People have studied it and reported back now. Mnholdem brings up a good point, the pediatric trial with the CGM could show superiority.
|
|
|
Post by oldfishtowner on Feb 21, 2017 10:17:30 GMT -5
The trial said Afrezza was non-inferior and their statement proves that is true for them. The next step is to have a trial to prove superiority. agedhippie,
I hope that the next step is for the FDA to reclassify Afrezza as a First-in-Class ultra-rapid/ultra-fast acting insulin. However, regarding your promoting a trial to demonstrate Afrezza's superiority to other insulin, it is entirely possible that MannKind's Chief Medical Officer (Dr. Urbanski) can demonstrate superiority using the pediatric trial, depending upon how the protocols are established.
Successfully meeting those endpoints would provide the "results" that you stated would convince the medical community and, regardless of anyone's viewpoint on mango's argument of a corrupt medical community, meeting superiority endpoints in a pediatric trial would make it very difficult for diabetes academics and/or KOLs to exclude Afrezza from any future discussions related to diabetes Standards of Care.
Urbanski must make sure that the primary and secondary endpoints are established in a way that, if Afrezza does NOT meet endpoints that establish superiority, the trial will still determine that it is safe and effective for pediatric treatment.
Isn't that what the time-in-range study is all about? A1c is the standard for measuring the effectiveness of diabetes drugs because none of the existing drugs have shown the capability to manage time-in-range the way Afrezza does. If the time-in-range study is successful, then maybe time-in-range will become the new standard of effectiveness. And, therefore, Afrezza will become the new standard of treatment.
|
|
|
Post by peppy on Feb 21, 2017 17:07:55 GMT -5
agedhippie,
I hope that the next step is for the FDA to reclassify Afrezza as a First-in-Class ultra-rapid/ultra-fast acting insulin. However, regarding your promoting a trial to demonstrate Afrezza's superiority to other insulin, it is entirely possible that MannKind's Chief Medical Officer (Dr. Urbanski) can demonstrate superiority using the pediatric trial, depending upon how the protocols are established.
Successfully meeting those endpoints would provide the "results" that you stated would convince the medical community and, regardless of anyone's viewpoint on mango's argument of a corrupt medical community, meeting superiority endpoints in a pediatric trial would make it very difficult for diabetes academics and/or KOLs to exclude Afrezza from any future discussions related to diabetes Standards of Care.
Urbanski must make sure that the primary and secondary endpoints are established in a way that, if Afrezza does NOT meet endpoints that establish superiority, the trial will still determine that it is safe and effective for pediatric treatment.
Isn't that what the time-in-range study is all about? A1c is the standard for measuring the effectiveness of diabetes drugs because none of the existing drugs have shown the capability to manage time-in-range the way Afrezza does. If the time-in-range study is successful, then maybe time-in-range will become the new standard of effectiveness. And, therefore, Afrezza will become the new standard of treatment. old fish tower, I always read what you have to say with interest. Time in range, the new standard. I want to comment on HgA1c. my comments on the hgA1c on the cynical side. Working in medicine, what a god send, a simple blood draw and number I can base all my decisions on and I have a life time patient on a life time drug, with a very 3 month blood draw to qualify for insurance coverage and one or more of the following drugs. www.screencast.com/t/nOwBa4aaA how convenient. The use of hemoglobin A1c for monitoring the degree of control of glucose metabolism in diabetic patients was proposed in 1976 by Anthony Cerami, Ronald Koenig and coworkers.
|
|
|
Post by agedhippie on Feb 21, 2017 18:43:45 GMT -5
Isn't that what the time-in-range study is all about? A1c is the standard for measuring the effectiveness of diabetes drugs because none of the existing drugs have shown the capability to manage time-in-range the way Afrezza does. If the time-in-range study is successful, then maybe time-in-range will become the new standard of effectiveness. And, therefore, Afrezza will become the new standard of treatment. Was there a time in range study? I missed that. Trial data from time in range would be a killer argument - both because fluctuations are important but also because it is almost impossible to get a bad HbA1c if you stay in range.
|
|
|
Post by compound26 on Feb 21, 2017 18:51:23 GMT -5
Isn't that what the time-in-range study is all about? A1c is the standard for measuring the effectiveness of diabetes drugs because none of the existing drugs have shown the capability to manage time-in-range the way Afrezza does. If the time-in-range study is successful, then maybe time-in-range will become the new standard of effectiveness. And, therefore, Afrezza will become the new standard of treatment. Was there a time in range study? I missed that. Trial data from time in range would be a killer argument - both because fluctuations are important but also because it is almost impossible to get a bad HbA1c if you stay in range. agedhippie Listen to Matt's presentation on Feb. 1 from 7'12'' on this. edge.media-server.com/m/p/wf9e94rm Note that Matt specifically said the Pediatric trial will start in this month (Feb. 2017). Below is what Ray said in last November in the third quarter conference call: We recently conducted an advisory board leading to identify ways to enhance and simplify the initiation of Afrezza in clinical practice. At the ad board they resoundingly felt that Afrezza differentiated pharmacokinetic profile made it an invaluable option for treatment of diabetes. Afrezza clears offers advantage to keep patients within a tight glucose target range, potentially leaning to less hyper and hyperglycaemias episodes. To accomplish this, however, the proper dosing and titration of Afrezza is a paramount importance because this is one of the areas that we have seen where healthcare providers struggle. To address these issues we are planning a 12-week to 16-week time and range dose optimization study in type 1 diabetics using CGM with Dexcom or the new Abbott Libre system. This study will be conducted in three to five of the most well-respected institutions in the country, adding credibility to the data and providing an immediate impact on clinical practice. We expect study start up to begin in the first quarter of 2017 with results sometimes in the fourth quarter. Additionally, we are planning a short pilot study for patients with type 2 diabetes that will allow us to simplify dosing initiation and titration. This will help patients get to the optimal dose quickly and effectively.
|
|
|
Post by sayhey24 on Feb 21, 2017 20:05:49 GMT -5
It sure would be nice for MNKD to get these studies done asap and we see some urgency. We can't afford any schedule slippage. First the Pediatric trial, they only have a week or so to announce this. Then a short T2 titration study, it would be nice to see this done with both the G5 and the Libre. I am not sure why this has not already started. Then we have the time and range which should be a game changer. It would be nice to see this also done with both the G5 and the Libre to see if there is a difference although only the Dexcom is approved for dosing.
|
|
|
Post by mango on Feb 21, 2017 20:42:08 GMT -5
It is of upmost urgency because if you will take notice, there are studies already taking place with CGM and insulin injections to establish related outcomes. It is going to be a fight to the finish.
|
|
|
Post by agedhippie on Feb 21, 2017 20:50:41 GMT -5
It sure would be nice for MNKD to get these studies done asap and we see some urgency. We can't afford any schedule slippage. First the Pediatric trial, they only have a week or so to announce this. Then a short T2 titration study, it would be nice to see this done with both the G5 and the Libre. I am not sure why this has not already started. Then we have the time and range which should be a game changer. It would be nice to see this also done with both the G5 and the Libre to see if there is a difference although only the Dexcom is approved for dosing. I think it has to be a G5 rather than a Libre as the Libre is only approved for blinded use. The Libre also has issues with correctly detecting lows which makes it unsuitable for this use.
|
|
|
Post by sayhey24 on Feb 21, 2017 21:42:39 GMT -5
It sure would be nice for MNKD to get these studies done asap and we see some urgency. We can't afford any schedule slippage. First the Pediatric trial, they only have a week or so to announce this. Then a short T2 titration study, it would be nice to see this done with both the G5 and the Libre. I am not sure why this has not already started. Then we have the time and range which should be a game changer. It would be nice to see this also done with both the G5 and the Libre to see if there is a difference although only the Dexcom is approved for dosing. I think it has to be a G5 rather than a Libre as the Libre is only approved for blinded use. The Libre also has issues with correctly detecting lows which makes it unsuitable for this use. I don't see it as either or, I would do two arms even if only the Dexcom arm can be submitted for the time and range for the FDA. The Libre is approved for patient readings only in consultation with the doctor. How that consultation is constructed and who doctor/PWD takes the readings is up to the doctor. It does not have to be blinded as some doctors are currently doing. There is little value for the PWD not seeing the readings real-time which is why some other doctors are having the PWD buy their own reader from the doctor and part of the consultation is for the PWD to keep a daily log which is reviewed in office every 2 weeks and compared with the readings done by the doctor. If MNKD can show as much value using the Abbott as the Dexcom this provides some leverage for MNKD with Dexcom and Dexom's partner Verily. Today, the Libre is much more affordable and fully covered by Medicare and provides a profitable business for the doctors replacing the sensors and reviewing the results every two weeks. Once MNKD proves time and range can be done and the shift starts away from A1c, Dexcom/Verily/Onduo needs afrezza more than MNKD need Dexcom. This time and range study is the make or break for MNKD but anyone who has been following afrezza as close as everyone on this MB already knows what the results will be. Place your bets as IMO these results will determine whether Matt needs to execute on the R/S which will be approved in a few days.
|
|
|
Post by mnholdem on Feb 21, 2017 21:52:46 GMT -5
Quick note: Seeking Alpha typically butchers transcripts (I sometimes wonder if the hire staff in India like my credit card company). The correct terminology for the new KPI discussed between the FDA and diabetes KOLs last summer is "Time in Range" rather than "Time and Range".
|
|