The most striking data that I was unaware of was the rates hypoglycemia in the type1 trial. I was impressed with not only the statistically and clinically significant less hypos with afrezza, BUT Al states that many afrezza patients were inhaling too early before their meals and causing low sugars. He did not comment about ONE singular patient causing most of the hypos, but he DOES have access to something WE do not....Source documents!! I can only imagine that info is shared with potential partners ($$$) and with the FDA (greater safety). The weight neutral issue is a given, the A1c reduction/non-inferiority is likely better with Afrezza than analogs once it is used CORRECTLY in the clinic. So hypoglycemia benefits alone are the reasons I believe FDA will approve Afrezza! This is a fundamental advantage over current RAA currently in the market. As long as FDA does not stumble over the non-significant reduction in lung function, they would be hard pressed to reject the drug.
sugarman005, I relistened to the Al Mann presentation at the JPM Healthcare meeting, and I think there can be no doubt Al thinks and forecasts hypoglycemic incidents with Afrezza, when type I or type II diabetics are properly instructed and learn when to use Afrezza, i.e., coincident with mealtime with no delay, there can be no hypoglycemic incidents caused by Afrezza. He even went on to say the only way for Afrezza possibly to cause a hypo would be to use Afrezza on an empty stomach and then not eat anything. The reasoning for this is the charts he showed with the almost instantaneous peaking of monomer insulin in the blood stream and the speed with which Afrezza is cleared from the blood stream. He is saying with proper Afrezza use hypoglycemic incidents are going to be a thing of the past. A cogent assertion for the FDA Advisory Committee to hear and ask questions about.
regarding the hypo's....the lower hypo incidents came at the cost of poor comparable a1c's. I think this, in part, is going to be the focus of the adcom. they did their aggressive basal titration (recall al repeatedly stating he thought basal was masking the benefits of Afrezza; oops) and still wound up w/ poor a1c comparisons to Arm 3. now he's suggesting the problem had to do w/ the timing of Afrezza dosing relative to the meals.
I don't know how mgmt. couldn't have let this happen.....but it did. No way in heck it's because the FDA wouldn't allow them to tell patients how to take Afrezza. No way.
"poor comparable A1c's" is statistically also non-inferior A1c's. You might agree that Statistically superior A1c may have been a closer goal had the Afrezza patients inhaled at the correct time and NOT prior to any meals (but AT the moment of eating). Yes aggressive basal titrations in type 1's usually causes only TWO things: Hypos and lower A1c's. But that aggressive basal titration should be equalized in the "control" method. FDA actually IS the "body" that dictates the protocol for the trials. If FDA said to use Afrezza prior to meals (similar to RAA) then MNKD had to follow this guideline. FDA has notoriously failed at designing appropriate Diabetes clinical trials to show clinically meaningful benefits. But this is not about the FDA or even MNKD, it's about Afrezza imo.
Let's assume patients all took Afrezza at the appropriate time (when eating). Do you suppose there would be MUCH les hypos, lower A1c's and even less weight gain as compared to RAA? I actually do believe this. I believe that the study protocol did NOT show the true benefits of Afrezza. I believe that the suboptimal protocol is plenty sufficient to provide FDA approval. This benefit will unfortunately not be known the providers who have yet to use Afrezza in the clinic. imo
You haven't heard? There's a village idiot here trying to make everyone believe the reason they inhaled too long before meals was because the fda prevented mnkd from telling patients how to use the drug. lol
not sure I understand...ok I will bite on this one.
FDA did not instruct MNKD in the protocol to use the Afrezza "bolus" timing any differently from the RAA arm "bolus" timing in either arm that I can recall. It makes sense that some patients (or maybe ONE patient) inhaled 20-30 minutes prior to meals as some do with Novolog and were not told that Afrezza does not work effectively at that time interval (since Afrezza has no package label). Most patients inject RAAs around 5 minutes prior to meals, give or take a few minutes (variable). But Afrezza is not variable in this time frame, it needs to be taken nearly at the time of meal ingestion. I am just saying, that Al has the source documents, not you or I. So if he states something in his presentation that we do not have knowledge of already, then we must infer that he is either telling us the source info or he is lying. Much of this information is proprietary and not publicly disclosed. Certainly potential partners and FDA has these documents already.
So ask me about hypos in the Type2 trial....
GLTU too OPC