For starters, Rapp78, the Letechdawg6's original 171 post is hard to follow due to guys like me jumping into the middle of the fray late last night, which caused Letechdawg6 to have to jump all around answering to 3 or more posters, so I recommend you ask your 175 study question(s) here.
You may wish to repeat your question to start the conversation.
thanks Dale. My main point for 171 is that you must compare the "glycemic effects" of each inhaler vs. the apart arm to prove bio =. This is what Al said in the conference call. And if you think about it, it makes perfect sense.
Bio = is proven by measuring the total units of insulin given by each inhaler vs. the resulting daily bg levels and monthly A1c average. For example, patients in both the DB arm and MT arm both eat 3 meals a day. They both take one basal injection per day and inhale before each meal (3X per day).
The DB inhaler uses 20 U per dose. The Medtone inhaler uses 30 U per dose. The only way to prove bio = is to measure the total daily doses of each inhaler vs. the daily bg fluctuations. You do this every day, every week and take an A1c test every 2 months or so (or whatever the protocol called for). The main bio = measurement is the A1c's of each inhaler vs. the aspart arm over a 24 week period. How else are you going to prove bio e? You must compare A1c levels of each vs. aspart as the measurement.
Of course, CV risk ratios, FEV, incidents of cough, etc. are also measured head to head, but it is the A1c comparison between the two inhalers which is the primary measurement for proving bio =.
Thus, MNKD refusal to publish the A1c results of Medtone is strange. Investors cannot gauge whether or not bio = is proven without them.
I'll also note that MNKD and the FDA have fought extensively over the criteria the FDA uses to define bio =. It was a major source of contention both before and after the last CRL.
MNKD knows exactly what they are yet they refuse to share them with us. So we are left to guess. But one thing I know for certain is you cannot prove bio = without comparing the "glycemic effects" between the two inhalers. Al said so himself during Q3 earnings release. "Glycemic effects" are daily blood glucose readings, hypos and monthly A1c readings. Non-glycemic effects are FEV, CV risk, cough, etc..
Rapp, seriously - who specifically have you talked to at the company that is stating that they brefuse top release anything? Do you have a name? My impression on the call was that they are still sifting data, and that they will be releasing more data . If you heard something different, such as an outright refusal to release specific data, I'd love to hear who your source is...
Part 2: Dreamboat Vs. Medtone
Continuing my effort to make nervous longs understand who BS the summer street claims are. This is expansion of my explanation from previous post "Dreamboat Vs. Medtone.. What FDA Wanted To Know..."
So some people argue that Mankind didn't release the data on how Medtone performed on reducing A1C reduction. For this discussion, lets assume that it did perform marginally or even significantly better than dreamboat. Since FDA didn't ask for that data as a part of trial design, doesn't mean they will not raise this issue in the next round of review.
Now lets understand why FDA designed the Affinity 1 the way it was performed. As a part of previous PIII studies of Afrezza with Medtone, MNKD tested 2500+ patients. They submitted massive collection of their chest data and lung function test data to support that it is completely safe and it doesn't impact FEV1 statistically significantly.
Now when MNKD decided to go with Dreamboat, FDA was not ready to accept that safety data collected in previous trails since it was with Medtone. So they asked MNKD to perform PIII studies but on a smaller scale to establish statistically significant FEV1 reduction so that they can comfortably ASSUME that the safety data (chest scans, FEV1 tests, Lung function tests) from previous trial is going to be same if the trails were conducted using Dreamboat.
At the same time they understood that when changing device, their main concern was safety. FDA did understand that Dreamboat may perform better or worst than Medtone when it comes to reducing A1C. But that is NON ISSUE. All they wanted to see is if Dreamboat performs NON-INFERIOR to insulin injection. and HENCE, they asked another arm to compare Dreamboat Afrezza and Insulin Asparte.
No if Medtone reduced A1c better than Dreamboat, Is FDA concerned? NO.. As long as Dreamboat is non-inferior.
Now, Will Afrezza be blockbuster? wait for my next post.
Part 1: Dreamboat Vs. Medtone.. What FDA Wanted To Know...
People here who do not understand what FDA wanted to know from Affinity 1 stand to loose here due to this panic cell created every day by picking different aspect of trail results..
All FDA wanted to know is if Dreamboat creates any lung function issue. The aeration of powder and the quality of powder + air mixture that is delivered to mouth depends on the device design equally as it depends on the powder technology (technosphere). I stand by FDA's CRL when they want MNKD to run P III with the device they plan to launch the product with.
So MNKD conducted PIII study and ONE of THE primary endpoint was to compare FEV1 performance between Afrezza with Medtone vs. Afrezza with Dreamboat. Mankind DID RELEASE the numbers on FEV1 comparing both the devices. FEV1 difference was 0.01 L which is insignificant.
The comparison from FDA perspective ends right there. The safety profile of dreamboat is same as medtone.
Now separately, dreamboat is proving non-infiriorty compared to injectable insulin in the same affinity 1 study with other arm. Now, even if medtone performed better in reducing A1C compared to dreamboat .. IT JUST DOESN'T matter.....
its none of FDA's business if MNKD wants to launch with Dreamboat even if it performed less than medtone in reducing A1C level AS LONG AS..... dreamboat is 1) as safe as medtone (FEV1 data released as mentioned above) 2) As effective as injectable insulin in reducing A1C level (which it is as per the data of Affinity 1 comparing A1C level with third arm of the study)
Bottomline, FDA will approve dreamboat irrespective of medtone's better performance on A1C reduction as long as FEV1 values are same. WHICH IT IS... SO people, have patience.. don't get manipulated... hold on to your stocks...
For last time, read the two posts I wrote earlier and stop asking irrelevant questions. NO you do not need to compare A1C performance of DB and Medtone. Just read two posts below.
Basic question: If Gen1 used a higher dose vs Gen2, why would one be surprised at a better result? Isn't the company planning a Gen2 trial with 30 U dosing? How then does the 171 outcome prove inferiority or questionable clinical utility?