Fiasp Cannot be Legitimately Labeled as Ultra-Rapid.

[mango]

~50% of daily endogenous insulin secretion in a healthy nondiabetic is postprandial. The first phase insulin response naturally begins after the beginning of a meal via the beta cells releasing an initial large sizeable rush of insulin. The first phase response occurs within a very specific physiological time-frame, and then follows into the phase two response.

The first phase insulin response occurs ~2 minutes after the beginning of a meal and continues for ~10-15 minutes where the serum concentration of insulin will have peaked. This large sizable rush of insulin thereby suppresses the hepatic glucose production and puts a lid on postprandial glucose levels. First-phase insulin secretion begins within 2 minutes of ingestion of a meal and continues for 10-15 minutes. The second phase of prandial insulin secretion follows thereafter.
These are the characteristics that Afrezza is able to mimic because Afrezza inhaled insulin reaches peak serum concentration within 12-15 minutes.

• Afrezza PK Profile




Now, in order for an exogenous insulin therapy to successfully mimic the endogenous first phase insulin response, it must reach peak serum concentration within the physiological normal time period, ~10-15 minutes. This is an essential part to glucose homeostasis in a healthy nondiabetic. Afrezza reaches peak serum concentration in 12-15 minutes. Fiasp reaches peak serum concentration well beyond the normal physiological time-frame permitted by any human body.

Turning attention to the below PK profile of Fiasp for a moment, one will notice wordings, such as—
"5.2 Pharmacokinetic properties
Absorption

"Fiasp is a mealtime insulin aspart formulation in which the addition of nicotinamide (vitamin B3) results in a faster initial absorption of insulin. Insulin appeared in the circulation approximately 4 minutes after administration (Figure 1). The onset of appearance was twice as fast (corresponding to 5 minutes earlier), time to 50% maximum concentration was 9 minutes shorter with Fiasp compared to NovoRapid with four times as much insulin available during first 15 minutes and with twice as much insulin available during the first 30 minutes."

• Fiasp Pharmacokinetics



• Continuous SC Fiasp Infusion Pharmacokinetics




It does not matter what the serum concentration is < 15 minutes, what matters is when the peak serum concentration is. Afrezza reaches peak serum concentration within 12-15 minutes, thus it successfully mimics the naturally occurring first phase insulin response and onto phase two it goes as well. Fiasp, on the other hand, does not reach peak serum concentration anywhere near the physiological boundaries acceptable by any human body.

Afrezza and Fiasp are two completely different insulins. Afrezza is an ultra-rapid acting insulin which mimics endogenous prandial insulin secretion like that in a healthy nondiabetic while Fiasp is simply another fast-acting injectable insulin.

[mnkdfann]

These labels are all man-made. Maybe Flasp is labelled ultra-rapid, Afrezza is Speedy-Gonzalez-rapid.

[peppy]

www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/004046/WC500220890.pdf

1 mL of the solution contains 100 units of insulin aspart* (equivalent to 3.5 mg).

6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients

Phenol  pubchem.ncbi.nlm.nih.gov/compound/phenol#section=Top

Metacresol    pubchem.ncbi.nlm.nih.gov/compound/m-cresol#section=Top

Glycerol
Zinc acetate
Disodium phosphate dihydrate
Arginine hydrochloride
Nicotinamide (vitamin B3)
Hydrochloric acid (for pH adjustment)
Sodium hydroxide (for pH adjustment)
Water for injections

So fiasp is insulin aspart with different excipients?

[mango]

Sept 18, 2017 14:20:36 GMT -5 mnkdfann said:

These labels are all man-made. Maybe Flasp is labelled ultra-rapid, Afrezza is Speedy-Gonzalez-rapid.

Fiasp cannot be legitimately called an ultra-rapid. That would be a lie. It's just another fast acting injectable insulin that does not mimic endogenous prandial insulin secretion.

[mango]

Sept 18, 2017 14:27:36 GMT -5 peppy said:

www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/004046/WC500220890.pdf

1 mL of the solution contains 100 units of insulin aspart* (equivalent to 3.5 mg).

6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients

Phenol
Metacresol
Glycerol
Zinc acetate
Disodium phosphate dihydrate
Arginine hydrochloride
Nicotinamide (vitamin B3)
Hydrochloric acid (for pH adjustment)
Sodium hydroxide (for pH adjustment)
Water for injections

So fiasp is insulin aspart with different excipients?

It's the same with the addition of two new excipients, Nicotinamide (for absorption) and Arginine hydrochloride (for stability). 

Its an unstable insulin formulation that is high risk for degradation and side effects considering the list excipients. 

Consensus: No thank you.

[mnholdem]

Ummm, I recall reading that the EMEA has already given Fiasp the "Ultra" classification. It's hard to predict whether the FDA will follow suit.

[itellthefuture777]

The diabetic takes the Fiasp 10 minutes before a meal...Afrezza is taken at the beginning of a meal...and even with that 10 minute head start for Fiasp...Afrezza peaks before Fiasp..and gets out before Fiasp..Like the Flash!

[dreamboatcruise]

Sept 18, 2017 15:01:26 GMT -5 mnholdem said:

Ummm, I recall reading that the EMEA has already given Fiasp the "Ultra" classification. It's hard to predict whether the FDA will follow suit.

I have mixed feelings on this topic.  I could make two arguments... and not sure which would win...

1) If Fiasp does get ultra-rapid, because of Novo's marketing muscle doctors may come to associate it's pd profile with ultra-rapid and thus discount the importance of the new class entirely and thus dilutes the benefit to Afrezza of the designation.

2) If Fiasp does get ultra-rapid, it benefits Afrezza because Novo's marketing muscle drums up interest in pd profile and then doctors do the research and discover that if fast is important as Novo would claim, they really should be prescribing Afrezza.

Of course it could be some of each occurs.

If Afrezza gets ultra but not Fiasp, then MNKD has to go it alone trying to convince doctors to consider the clinical benefit of faster pd profile... but if MNKD could get over the market penetration "chasm" this might be the best outcome on labeling for the long run market capture.

[mango]

Sept 18, 2017 15:01:26 GMT -5 mnholdem said:

Ummm, I recall reading that the EMEA has already given Fiasp the "Ultra" classification. It's hard to predict whether the FDA will follow suit.

This website says rapid acting. 

www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/004046/human_med_002063.jsp&mid=WC0b01ac058001d124

[mango]

Sept 18, 2017 15:14:47 GMT -5 dreamboatcruise said:

Sept 18, 2017 15:01:26 GMT -5 mnholdem said:

Ummm, I recall reading that the EMEA has already given Fiasp the "Ultra" classification. It's hard to predict whether the FDA will follow suit.

I have mixed feelings on this topic.  I could make two arguments... and not sure which would win...

1) If Fiasp does get ultra-rapid, because of Novo's marketing muscle doctors may come to associate it's pd profile with ultra-rapid and thus discount the importance of the new class entirely and thus dilutes the benefit to Afrezza of the designation.

2) If Fiasp does get ultra-rapid, it benefits Afrezza because Novo's marketing muscle drums up interest in pd profile and then doctors do the research and discover that if fast is important as Novo would claim, they really should be prescribing Afrezza.

Of course it could be some of each occurs.

If Afrezza gets ultra but not Fiasp, then MNKD has to go it alone trying to convince doctors to consider the clinical benefit of faster pd profile... but if MNKD could get over the market penetration "chasm" this might be the best outcome on labeling for the long run market capture.

Would the FDA not declare the distinction between ultra-rapid and fast-acting if the new class is made? I would think they would have important information in the PR. 

Anyways, Endos should know what the hell glucose homeostasis is why it's important to have an insulin that mimics endogenous prandial insulin secretion. If they must rely on a corrupt Pharma company to teach them then we have an entirely different problem.

[matt]

Sept 18, 2017 15:21:32 GMT -5 mango said:

Would the FDA not declare the distinction between ultra-rapid and fast-acting if the new class is made?

Yes.  If FDA wants to introduce a new class description, then they first have to define precisely what they mean by that new adjective, and secondly decide if Afrezza and/or Fiasp qualify.  That first definition is critical because if, in fact, an ultra designation is commercially valuable then everybody else is going to want to have it and there must be clear, objective, quantifiable criteria for allowing or rejecting the claim by others.  FDA will also have to decide what time difference is clinically relevant, which again has to be an objective and quantifiable measure.  Personally, I think getting the FDA to declare a new class of insulins will be the hard part.

[tchalaa]

Fiasp is a medicine that is used to treat adults with diabetes. It contains the active substance insulin aspart, a rapid-acting insulin.

Source: www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/004046/human_med_002063.jsp&mid=WC0b01ac058001d124

[dreamboatcruise]

mango

"Would the FDA not declare the distinction between ultra-rapid and fast-acting if the new class is made?"

Don't think I'd venture a guess on that one. My crystal ball is out at the shop for its annual polishing and tuning. If the FDA channel is working on it when I get it back, I think I can make a fortune predicting what the FDA will do.

[dreamboatcruise]

Sept 18, 2017 15:34:19 GMT -5 matt said:

Sept 18, 2017 15:21:32 GMT -5 mango said:

Would the FDA not declare the distinction between ultra-rapid and fast-acting if the new class is made?

Yes.  If FDA wants to introduce a new class description, then they first have to define precisely what they mean by that new adjective, and secondly decide if Afrezza and/or Fiasp qualify.  That first definition is critical because if, in fact, an ultra designation is commercially valuable then everybody else is going to want to have it and there must be clear, objective, quantifiable criteria for allowing or rejecting the claim by others.  FDA will also have to decide what time difference is clinically relevant, which again has to be an objective and quantifiable measure.  Personally, I think getting the FDA to declare a new class of insulins will be the hard part.

If what you say is true... that they would have to have a bright line criteria first, then unfortunately I'd suspect they may delay the decision.  And as you've stated it could be asking MNKD... "Are you willing to have this put on hold while we investigate further, or do you want us to say no now?"

I'm assuming that you know this is what happened with defining RAA as a class... they set specific speed criteria first and then evaluated insulins against it?  What are the criteria?

[tchalaa]

There is currently a new class according to a market research document: "ultra short acting insulin" and this can only be in prelude of an announcement because the performance is known already in the elite diabetes circle.
Source: peopleexclusive.com/global-insulin-market-2017-novo/

Fiasp has recently received the EMEA designation "Rapid-acting insulin" and seeking for fast acting insulin from the FDA. Afrezza is ultra short acting insulin according to data collected during a study pd/pk fast in fast out ALMOST like a healthy pancreas
The criteria for this designation should not be the issue since the benchmark this this time will be a healthy pancreas and we have CGM already approved as medical device for data collection.


Now let the FDA talk mannkind future !!