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Post by silentbob on Mar 31, 2014 5:06:04 GMT -5
Dosing conversion proposed in the label is a big issue in my mind because the FDA has been real negative on the proposed change by Mannkind.
Worse, I kind of agree with the FDA. While MNKD may just want to make conversion more user friendly, they don't seem to have enough data to back up the change. At the lower doses especially the change may not be suppiorted by the data.
There is probably no harm in inhaling some excess Afrezza because of the low hypo risk, but the FDA works strictly evidence based so that argument is unlikely to hold up.
I haven't read everything yet and I did not even get started on the MNKD document, but dosing stood out as one of the bigger potential issues.
I hope MNKD has kept its options open and can simply switch back to the old dosing method during label negotiations before April 15, because things like this have the potential to cause trouble. While it is unlikely to cause more than a minor delay, let us hope MNKD has the sense to make approval without delay their top priority and accommodates the FDA where needed.
Anybody have any insight in this issue? Did you read MNKD's side on this?
Note that I will handle each relevant FDA-raised issue in a separate post in the hope each one will get its own proper discussion, and so that I can spread out my posts over the day.
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Post by esstan2001 on Mar 31, 2014 10:32:10 GMT -5
Do not recall Mannkind's take on dosing in their document.
(Was the first thing I downloaded from FDA site, sped thru it, and thought the FDA was in love... next, I then saw the FDA's BrfDoc...)
Assuming tomorrow's presentations go well, and the vote is not bad What gates do we need to get thru for approval?
1. FDA has to be willing to allow Mannkind to go back to the dosing used in Gen2 trial... can this be accomplished just via discussion & labeling?
2. FDA (begrudgingly) accepts endpoints in trials
3. FDA looks at data measuring of glycemic levels in patients / deems value to the limited excursions... this in conjunction with the totality of A1C data gets them over the hurdle for both indications....
1- I can see happening without requiring another CRL... Opinions?
2- Plausible this can happen for T2, not sure about T1 trial (50/50).
3- So was such data collected? Was it submitted in the filing? If not, will be presented tomorrow?
1 & 3 are gnawing at me... all thoughts from anyone are welcome
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Post by babaoriley on Mar 31, 2014 10:42:16 GMT -5
Dosing is so basic (I mean, completely intrinsic to all trials, I would think), I find it difficult to believe that now, it's toward the top of everyone's list of horrors. How can that be?
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Post by jpg on Mar 31, 2014 10:59:13 GMT -5
Hi Babaoriley,
For some reason I thought I posted here about this very subject following SilentBob? I must be loosing it on this last trading day before V day (hopefully). I have posted a lot yesterday on this very subject and come to a different conclusion as to the significance of this for the panel members. Without repeating my rambling posts again I don't think this is a big clinical issue and I am certain Mannkind will (hopefully) do whatever the FDA wants on this: 3/10 great! 4/10 great! It doesn't matter other then in the very early stage of switching and the patient and clinician will look at glucose levels more then anything else anyway. The drugs are so different in profile that there is no right or wrong answer (10% margine of error is not so bad) to this biologically complex question. what will be on the conversion label? Hopefully whatever the FDA want Mannkind to put there...
If this is our biggest issue we are good...
JPG
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Post by esstan2001 on Mar 31, 2014 14:02:38 GMT -5
jpg, you already posted a good response to this- however I kept it alive, dredging it up here and there.
My bad :-)
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Post by silentbob on Mar 31, 2014 14:17:10 GMT -5
Dosing is so basic (I mean, completely intrinsic to all trials, I would think), I find it difficult to believe that now, it's toward the top of everyone's list of horrors. How can that be? Because it is an unknown? We have no idea if MNKD will stick to its guns, as they did with the Dreamboat switch. Not that I am overly concerned, but it is a risk. |
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Post by babaoriley on Mar 31, 2014 14:46:22 GMT -5
"If this is our biggest issue we are good..."
Thanks for your reply, jpg!
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