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Post by james on May 4, 2015 19:33:26 GMT -5
Given the high patient interest, Sanofi / Mannkind are probably already evaluating the 2U cartridge option. I have even read a post from a patient who has occasionally hacked together their own 2U cartridge! What concerns me about the 2U is that it walks back somewhat on the idea that hypoglycemia risk is reduced on Afrezza (though we know that some users have gone low with it). Another element is that the 2U would step up the uncertainty when choosing a dose. If a patient knows they should take at least 4U but are considering 8U, should it really be 6U? Perhaps at that point they would need to reevaluate the carb intake... Now, clinically 2U/6U/10U might be more optimal levels for many patients, so this is certainly a high priority item (and I want what is best for the patient). But, also why stop there; is a 1U or .5U cartridge necessary? At that point, the patient would need to carry a whole collection of cartridges for the day rather than a select few. The whole dosing simplicity model can get out of control on that path. This needs to be approached cautiously to ensure that dosing simplicity remains a positive feature of the product and that patients are comfortable with that idea when deciding whether to initiate the therapy. Further, the current label was approved with dosing ranges based on 4U increments. Adding a 12U cartridge doesn't affect this as it was already an option by adding a 4 and 8. A 2U cartridge would be a different animal in respect to the label and that may not be an easy discussion with the FDA who will have the same questions. So, can this be added without a study? What are the opinions? Edit: I missed that there was a thread on this a week or more ago - see also mnkd.proboards.com/thread/2266 |
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Post by kball on May 4, 2015 19:59:32 GMT -5
I want to say i think i recall...but can't be sure...an article or interview with Al (was it Amy's 09 interview) where Al did not envision producing a 2 unit cartridge though.
I cant be sure i'm remembering this correctly.
Any input from someone younger and smarter?
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Post by tigiron on May 4, 2015 20:04:44 GMT -5
I have even read a post from a patient who has occasionally hacked together their own 2U cartridge! Now, clinically 2U/6U/10U might be more optimal levels for many patients, so this is certainly a high priority item (and I want what is best for the patient). But, also why stop there; is a 1U or .5U cartridge necessary? At that point, the patient would need to carry a whole collection of cartridges for the day rather than a select few. The whole dosing simplicity model can get out of control on that path. This needs to be approached cautiously to ensure that dosing simplicity remains a positive feature of the product and that patients are comfortable with that idea when deciding whether to initiate the therapy. Further, the current label was approved with dosing ranges based on 4U increments. Adding a 12U cartridge doesn't affect this as it was already an option by adding a 4 and 8. A 2U cartridge would be a different animal in respect to the label and that may not be an easy discussion with the FDA who will have the same questions. So, can this be added without a study? What are the opinions? Do you have the link or keywords to google for the 2 u hack? I thought about that and speculate patients might figure out ways to half inhale, even without hack --- like smoking cigarette. I was also pondering a design where a cartridge can be use as 8u a shot or 2x4u, just by adding a switch or 2 openings, etc. I don't think that is hard to do. In fact, for efficacy, I suspect that splitting a 8 u into 2 4u inhale would both be safer and lower more BG levels. For adults, if afrezza works as it is being advertised at the moment, I think 2 u is probably as low as you need to go. Since patients have only 4u option at the moment, and they have experimented with it thoroughly, they probably would accept 2 u as quite safe for most cases. With the 4 U prelude, psychologically most patient would agree that 2 u would be the minimum and most would find out that would be the case. If 2 u requires a separate FDA trial, I would say the FDA is scientifically illiterate, those statisticians at FDA knows only about numbers, and clueless obviously about science. The fact of the matter is that human biological processes are not exact science, as long as they are bounded in some reasonable physiological range, it is safe and it should work. If FDA scientists really have any common sense, 2 U would be safer --- one 2 U inhale would definitely lower (slightly) LESS than what one 4 u would do, hence no safety issue with regard to its proposed/anticipated purpose of usage. A basic understanding of human physiology and insulin mechanism would suffice --- the current dosage scheme is consistent with this. |
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Post by james on May 4, 2015 20:26:25 GMT -5
How the 2U 'hack' was done was not described. There was merely mention of it having been done. It may be as simple as dumping some powder from an unused cartridge into a used empty one.
I think the switchable 'dial-a-dose' cartridge design is possible to manufacture and may have some advantages. I can't imagine this would be taken up for numerous reasons. Chief among these is that the current inhaler has been approved and fiddling with it would be a folly.
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Post by james on May 4, 2015 20:48:02 GMT -5
For adults, if afrezza works as it is being advertised at the moment, I think 2 u is probably as low as you need to go. Since patients have only 4u option at the moment, and they have experimented with it thoroughly, they probably would accept 2 u as quite safe for most cases. With the 4 U prelude, psychologically most patient would agree that 2 u would be the minimum and most would find out that would be the case. I pretty well agree with this from an outsider point of view. I've certainly never had to deal with diabetes, so knowledge is limited in that respect. There is probably a concern with under dosing and the whole element of reducing glucose liver production during digestion and any myriad of other complicating factors. I really don't know how to approach those thoughts... I sense that patient suggestions around the 2U desire are mostly related to corrections and snacks rather than meal-time. |
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Post by tigiron on May 4, 2015 20:51:01 GMT -5
How the 2U 'hack' was done was not described. There was merely mention of it having been done. It may be as simple as dumping some powder from an unused cartridge into a used empty one. I think the switchable 'dial-a-dose' cartridge design is possible to manufacture and may have some advantages. I can't imagine this would be taken up for numerous reasons. Chief among these is that the current inhaler has been approved and fiddling with it would be a folly. FDA is doing a disservice to innovations by their stupid overreach while let those selling snake oil sneak through. A one load two inhale design could be really simple: two chambers each with one openings, and the switch would control if one(first then second), two are to be inhaled. How this would require additional clinical trial is beyond me. Well, maybe FDA should require clinical trial for syringe/needles. Same 8 u injection, by different syringe/needles would have substantially different effect? --- technically needles are of different diameters, hence the lengthy and costly trials to find out? Sometimes they need to use some common sense. Al Mann at some point say openly that the FDA is suppressing innovation. Lantus, Humalog, Novolog, and Apidra when in clinical trial, none of them demonstrated any A1c advantage, and that should be expected and exactly why they are better --- older insulins fluctuate too much, low hypo level BG of course would contribute to lower A1c when averaged. How this would be difficult for FDA stuff to understand and accept? |
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Post by babaoriley on May 4, 2015 21:19:18 GMT -5
I would think a two unit size would be a snap, even with the FDA being the arbiter; once they get the next two lines running, perhaps they go after that. Here's the thing, though, MNKD/Sanofi may feel it's unnecessary because one can take a corrective/supplemental dose of 4 units without danger, given the rapid ingress and egress.
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Post by savzak on May 4, 2015 22:14:44 GMT -5
Here's the thing, though, MNKD/Sanofi may feel it's unnecessary because one can take a corrective/supplemental dose of 4 units without danger, given the rapid ingress and egress. I think that's exactly why there has been no plan for a 2U cartridge. |
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Post by jpg on May 4, 2015 22:16:52 GMT -5
If knowledgeable diabetics ask for a 2 unit version for corrections I hope Sanofi and Mannkind are smart enough to listen and not wait for the paediatric trials. Telling them they don't need it is not wise... Maybe not role it out now (the can't anyway as it probably and likely has to go through a study) but make it clear that their requests are heard and that Sanofi will do this.
Many type 1s can't take a corrective dose of 4 units without going into hypo ranges. Some smaller women can't take 4 units for an average meal. These patients know what they are doing and we all would be wise to listen to the real experts. We need a 2 unit version for kids. Might as well do it earlier than later if our major user group (type 1s) want that option.
Carrying around 2-4-8 unit options is a lot less complicated then carrying around all the stuff diabetics now have to carry around for mealtime insulin. Giving type 1s more options in dosage certainly is in our interest. Hopefully Sanofi will not let their interpretation of inhaled insulin pk/pd get in the way of actual user needs.
A study of correction dosing could be designed for approval of 2 units and for label improvement at the same time. Imagine the study in type 1s: injected rapid acting prandials with corrections by injected prandials vs Afrezza mealtime with 2 or 4 units for corrections and the whole thing monitored by CGM. Probably and sadly the FDA probably wouldn't allow a CGM to be used (they live with dinosaurs) but it would be one amazing study and we could get superiority in label and a 2unit dosing all in one study. Now who would pay for that? Yeah...
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Post by tchalaa on May 5, 2015 3:58:35 GMT -5
I find it interesting to discuss about the 2-unit dose but until now we haven't seen emerge the real need and I strongly believe according to the Mannkind-Sanofi agreement on AFREZZA that Sanofi will make sure the 2-unit dose is used in the pediatric trial.
What is approved for children is as well for adults most of the time but NEVER the other way round
For adult, 10 years of research have identified an average need of 12-unit therefore it was smart to come out first with the 8-unit dose and the 4-unit one mostly for adjustment (my opinion).
I, personally, look at the 12-unit dose more of like a convenient dose, reducing the quantity of cartridges being carried along all day long (though still very discreet compare to a pen).
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Post by traderdennis on May 6, 2015 4:35:29 GMT -5
My wild ass guess is that 2U is linked to an under 18 (<12) dose and will not be approved for general use until childrens use is approved.
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Post by ezrasfund on May 6, 2015 5:34:57 GMT -5
I asked Matt about this. His e-mail response yesterday: "We are considering it. We really don't think it is needed for the type 2's we are servicing now, but the fanatical type 1's might use it to deal with snacks. It might also be needed for kids."
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Post by savzak on May 6, 2015 5:47:29 GMT -5
I asked Matt about this. His e-mail response yesterday: "We are considering it. We really don't think it is needed for the type 2's we are servicing now, but the fanatical type 1's might use it to deal with snacks. It might also be needed for kids." I'm sure he didn't intend any disrespect or insult by using the word "fanatical", but there are many adjectives that would have worked better. |
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Post by kball on May 6, 2015 6:49:38 GMT -5
I asked Matt about this. His e-mail response yesterday: "We are considering it. We really don't think it is needed for the type 2's we are servicing now, but the fanatical type 1's might use it to deal with snacks. It might also be needed for kids." Hooray! Thanks Ezra Somewhere there supposedly are T2's they are "servicing"!!! However, if this was posted by some random poster on YMB instead of Matt, i sure would be skeptical and want proof backing it up. Also, and this is just my preference, but i'd use a different word than 'servicing'...perhaps 'serving' or 'reaching'. 'Servicing' has that massage parlor 'happy ending' vibe to it. Come to think of it...things have been a bit stressful of late. Gotta go make a phone call. |
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Post by mnholdem on May 6, 2015 10:27:52 GMT -5
Maybe you'll get a smile back on your avatar (chuckle). It does look a little weird without the mouth.
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