I've not read the board much lately because we're clearly in a trading lull and waiting on the trial results. I did just now see this talk about Affinity 1 results. My question is this...is there any evidence of any type, any shred of discussion from a blog or anything at all, that Affinity 1 results are lacking? Or is that notion just the premise for a discussion inducing hypothetical on this board? Thanks.
Sentiment: Strong Buy
Thanks for the responses. I didn't mean to imply that I'm concerned about the trials. I am not. I just wondered whether some blog or hack piece had issued since I saw people discussing the point. Apparantly there was no such source for the discussions in those threads. Apparantly those discussions were just hypotheticals, which is fine...I just wanted clarification.
Sentiment: Strong Buy
I just posted this in response to another message:
It is EXTREMELY unlikely that negative results could be leaked, simply because negative results are extremely unlikely to begin with. As Rapp states, it will be very difficult (or just about impossible) to show statistically significant superiority in Affinity 1. By the exact same logic, it will be equally difficult (almost impossible) to get a statistically INFERIOR outcome. As per 009 and 117, and given the strict control of fasting bg levels and aggressive basal titration, there is a very high likelihood that the results will be within the 0.5 margin of non-significance, i.e. it will be called non-inferiority, regardless of one of the other being slightly ahead. JMHO
thanks for posting this as a reminder.
Just based on 009 and 117 it seems there is a clear trade-off between the aggressiveness of basal titration (and thus A1c control) and the number of hypos. This is true for both, Afrezza and RAA. Despite what Al is saying (and he probably knows a lot more about this than me or even Rapp), my feeling is that A1c levels are almost completely unaffected by the pharmacokinetics of the prandial insulin or by glucose excursions, and completely depend on the overall average glucose in the blood over time (which would be about the same for similar dosage of RAA and Afrezza). If I am right, it is still the case that it would be equally unlikely for Humalog to show superiority as it would be for Afrezza. I disagree with Rapp's hypothesis that Afrezza could realistically fail in Affinity 1, whereas it has almost no chance of proving superior. In the worst cast, both of these outcomes are equally and extremely unlikely. In the best case, Al is right and Afrezza could prove superior. JMHO.
Kepler,I hear what you and rapp are saying but when I read what Al says I get the impression that nobody told him that Affinity 1 can't show superiority.
Al(Q3,2012 earnings call):
The main objectives of MKC-171 are to bridge our next-generation Dreamboat delivery device to the data from the earlier trials conducted with the MedTone inhaler and to compare the glycemic effects with the patients -- those with the rapid-acting analog. The primary endpoint for approval is simply not inferiority for the latter comparison, though a secondary endpoint is defined as superiority. The protocol calls for titrating the basal insulin to lower fasting glucose to under 120 milligrams per deciliter. Although the -- in the event of a hypoglycemic event, titration is to be terminated.
Patients on AFREZZA, who are compliant in meeting the fasting glucose target should reach near-normal A1Cs, whereas almost all patients are rapid-acting analogs for those fasting glucose likely could not be safely lower that significantly.
to be continued
Treat to target should ensure effectiveness with a reasonable # of hypos... failure is not a huge concern of mine. MNKD also had a huge rally while the trials were going on, and I highly suspect that Wall Street had eyes on the likely outcome. Anything can happen I guess, but bad data is highly unlikely.
The market was looking for better a1c numbers. Many are choosing to await approval before risking their money. Some see opportunity, some don't care to put their money at risk. If you recall Al was hyping lower a1c results in some presentations. He reasoned that they were too careful in their first trials and that led to the poor a1c numbers. He confidently assured his listeners the a1c numbers would be better. As we all know, the FDA could go either way. I used to be sure they would approve Afrezza,, but now I am much less sure. I reduced my holdings, but still hold some shares.