|
Post by peppy on Jul 14, 2016 16:59:54 GMT -5
The day of those results will be a vicious move but given what MNKD has gone through I can't see the FDA approving this on a 30 person trial. I hope to be proven wrong. FDA is fairly practical on these matters, and whether a 30 patient trial is enough depends on the particular label change. The pharmacodynamics data that FDA approved in the label was developed from just 12 patients so if there is a cohort of 30 that gives a different (but not totally different) answer then it might be enough.
The tricky bit is that there is one set of claims in the label that were agreed to based on data that was claimed to be reliable. If there is new, and different, data then it is fair for FDA to ask some tough questions like:
"Do we believe the data you showed us when we approved the drug, this new data, or should we make you run a trial of 100 patients to break the tie before deciding?"
"If you say the new data is reliable but the old data was not, does that mean everything we based the approval on should be considered unreliable?"
Answers to those questions are not easy. Changes in labels always open a can of worms and the answer might not be what shareholder want. Still, given where the company is the risk is probably worth it if there is chance to improve sales.
consider what seems unreliable is the fast acting data. Perhaps the, "If you say the new data is reliable but the old data was not, does that mean everything we based the approval on should be considered unreliable?" should be asked of the fast acting labels, lispro, etc. The knife cuts both ways doesn't it?
|
|
|
Post by agedhippie on Jul 14, 2016 17:34:38 GMT -5
Just generally there are a few things that people overlook when they talk about Afrezza because they don't use SC insulin. The focus is always on needles and injecting in public and those benefits are a long way down most insulin users lists. I don't think I have ever seen anyone talk about the preservatives used insulin ( meta-cresols) which is why some people get injection site reactions, or nickel allergies which are difficult as most needles are stainless steel. Even absorption is far more important than fast clearance, if I have predictable absorption I can safely stack insulin. Minor rant over! I'm not sure that even absorption is far more important than fast clearance. I'd agree that they are both important. It's good that Afrezza has both, but I'm sure you could just evenly distribute your 1 shot into many shots across your body to get the same effect -- kind of like the picture of the girl with all the shots at once or possibly creating Mrs. Captain America... Also, you can unsafely stack insulin. That's the rub. I'll expand on that. If absorption is predictable so is the action. Humalog has a 4 hour life with me and as near as makes no difference in hourly chunks the remaining insulin from a 4u shot goes 3,2,1,0. If I need to take insulin at the three hour mark I have to remember to deduct 1u from the dose to account for insulin on-board (IOB). If the absorption rate is uneven I may nor may not have 1u left when I take that second bolus which will change where I finally come to rest after the second bolus. Predictable absorption means that goes away so I always end up where I want to be and I can happily stack insulin. In the real world (or my version of it) I want to be able to eat when I want and stacking allows that. Fast clearance is nice because it reduces the timeframe for variance but if there is no variance then that has less value. My meter tells what my IOB, what my levels are, and if there is going to be an undershoot or overshoot and by how much (pumps aside there is only one meter in the US with this function. There are a lot in Europe that do it but the makers always disable IOB in the US because the FDA is much slower to approve meters with that function and the makers don't want to delay time to market).
|
|
|
Post by peppy on Jul 14, 2016 19:45:47 GMT -5
I'm not sure that even absorption is far more important than fast clearance. I'd agree that they are both important. It's good that Afrezza has both, but I'm sure you could just evenly distribute your 1 shot into many shots across your body to get the same effect -- kind of like the picture of the girl with all the shots at once or possibly creating Mrs. Captain America... Also, you can unsafely stack insulin. That's the rub. I'll expand on that. If absorption is predictable so is the action. Humalog has a 4 hour life with me and as near as makes no difference in hourly chunks the remaining insulin from a 4u shot goes 3,2,1,0. If I need to take insulin at the three hour mark I have to remember to deduct 1u from the dose to account for insulin on-board (IOB). If the absorption rate is uneven I may nor may not have 1u left when I take that second bolus which will change where I finally come to rest after the second bolus. Predictable absorption means that goes away so I always end up where I want to be and I can happily stack insulin. In the real world (or my version of it) I want to be able to eat when I want and stacking allows that. Fast clearance is nice because it reduces the timeframe for variance but if there is no variance then that has less value. My meter tells what my IOB, what my levels are, and if there is going to be an undershoot or overshoot and by how much (pumps aside there is only one meter in the US with this function. There are a lot in Europe that do it but the makers always disable IOB in the US because the FDA is much slower to approve meters with that function and the makers don't want to delay time to market). Aged, do you give any credence in reports that people on afrezza say they feel better? Sam as an example.
|
|
|
Post by agedhippie on Jul 15, 2016 7:58:47 GMT -5
I'll expand on that. If absorption is predictable so is the action. Humalog has a 4 hour life with me and as near as makes no difference in hourly chunks the remaining insulin from a 4u shot goes 3,2,1,0. If I need to take insulin at the three hour mark I have to remember to deduct 1u from the dose to account for insulin on-board (IOB). If the absorption rate is uneven I may nor may not have 1u left when I take that second bolus which will change where I finally come to rest after the second bolus. Predictable absorption means that goes away so I always end up where I want to be and I can happily stack insulin. In the real world (or my version of it) I want to be able to eat when I want and stacking allows that. Fast clearance is nice because it reduces the timeframe for variance but if there is no variance then that has less value. My meter tells what my IOB, what my levels are, and if there is going to be an undershoot or overshoot and by how much (pumps aside there is only one meter in the US with this function. There are a lot in Europe that do it but the makers always disable IOB in the US because the FDA is much slower to approve meters with that function and the makers don't want to delay time to market). Aged, do you give any credence in reports that people on afrezza say they feel better? Sam as an example.
If they are getting better control, which seemed to be the case with Sam, then yes definitely. Running higher levels, or rapid changes in levels makes you feel slightly ill.
|
|
|
Post by sweedee79 on Jul 15, 2016 10:11:45 GMT -5
For my dad it didn't give him better control becuz he wasn't on the right dose... but as a matter of fact he did feel better.. he lost lots of weight .. had more energy and his blood pressure went down. I can only say that the difference was that the insulin didn't hang in his body the way that novolog does.. Afrezza is a more natural treatment. Since going back on Novolog he has gained all of his weight back and he has no energy once again and on top of that he is angry becuz he knows there are meds out there that aren't available to him, either too expensive.. or not covered by insurance... or docs don't want to deal with it ..
|
|
|
Post by agedhippie on Jul 15, 2016 10:27:09 GMT -5
For my dad it didn't give him better control becuz he wasn't on the right dose... but as a matter of fact he did feel better.. he lost lots of weight .. had more energy and his blood pressure went down. I can only say that the difference was that the insulin didn't hang in his body the way that novolog does.. Afrezza is a more natural treatment. Since going back on Novolog he has gained all of his weight back and he has no energy once again and on top of that he is angry becuz he knows there are meds out there that aren't available to him, either too expensive.. or not covered by insurance... or docs don't want to deal with it ... It's hugely frustrating as a diabetic to have changes forced upon you. Your focus is on dealing with diabetes in the most effective way possible, the insurers focus is on doing it as cheaply as possible. I could cheerfully throttle the insurers at times because they patently don't understand what they are talking about (some time try and get a pharmacist rather than a packer or pharmacy technician at a PBM, it's a fight).
|
|
|
Post by rockstarrick on Jul 15, 2016 14:55:11 GMT -5
The day of those results will be a vicious move but given what MNKD has gone through I can't see the FDA approving this on a 30 person trial. I hope to be proven wrong. FDA is fairly practical on these matters, and whether a 30 patient trial is enough depends on the particular label change. The pharmacodynamics data that FDA approved in the label was developed from just 12 patients so if there is a cohort of 30 that gives a different (but not totally different) answer then it might be enough.
The tricky bit is that there is one set of claims in the label that were agreed to based on data that was claimed to be reliable. If there is new, and different, data then it is fair for FDA to ask some tough questions like:
"Do we believe the data you showed us when we approved the drug, this new data, or should we make you run a trial of 100 patients to break the tie before deciding?"
"If you say the new data is reliable but the old data was not, does that mean everything we based the approval on should be considered unreliable?"
Answers to those questions are not easy. Changes in labels always open a can of worms and the answer might not be what shareholder want. Still, given where the company is the risk is probably worth it if there is chance to improve sales.
Thanks Matt, it was worth the week wait to get this answer, it does seem that these post approval evaluations are meant to identify negative adverse side affects to add to the label, rather than use them for label improvements. i guess we can at least hope they feel the need for a more accurate label in this case. Thanks again !!
|
|