CME Hilton Santa Clara 12/10/15: Ultra RA Afrezza

[lakers]

Three New Insulins Recently Added To
Our List Of Options*
Both approved by the FDA and now available for patients
1. U-300 glargine (Toujeo) a long acting basal insulin
2. U-100/200 degludec (Tresiba) a long acting basal insulin
3. Technosphere Inhaled insulin (Afrezza) an ultra rapid acting inhaled insulin

Prandial Dosing In Type 2 Diabetes
• Start with 4 to 5 units or 10% of the total basal dose, of a rapid acting analog or inhaled insulin
• Add 2 units every 3 days if median BS before the next meal or bedtime (only for the pre- dinner dose) until at goal (140 to 180mg/dl)
• Add 1 unit every day if the BS before the next meal or bedtime (only for the pre-dinner dose) until at goal (140 to 180 mg/dl)
• Reduce the dose by 2 units if patients has hypoglycemia below 70 mg/dl

tcoyd.org/PDF/2015-postp-santaclara-slides.pdf

Insulin Human (Afrezza)
Compared with other rapid-acting insulins:
• Peaks faster and offsets faster
• When added to basal insulin, equivalent A1C lowering • Lower postprandial blood glucose
• Less delayed hypoglycemia
Can be used in Type 1 diabetes in addition to a basal insulin (long acting insulin or basal rate via an insulin pump)
Can be used in Type 2 diabetes in addition to orals alone, orals and basal, or MDI regimens
Clin. Ther., 2014;Vol 36:Number 8: 1275-1289.

Prandial Dosing In Type 1
Insulin to Carbohydrate Ratio
Calculation: I:CHO
(Type 1 and Type 2 on MDI)
} Start with a ratio of 1:15 for insulin sensitive type 1 diabetics
} Start with a ratio of 1:10 for insulin resistant type 2 diabetics
} Formula: divide Total daily insulin dose into 500 } Example: 34 year old male with type 1 diabetes
currently on 25 units of glargine (Lantus) every night and 20 to 25 units of aspart (Novolog) each day: 500/50=10 So the initial Insulin to carb ratio is 1:10

Correction Factor (CF)
or Insulin Sensitivity Factor (ISP)
(Type 1 andn Type 2 on MDI)
Giving your patients a correction factor is a very practical tool whether they are on a pump or not
The CF is an estimate of how much the BS will drop with one unit of fast acting insulin
The CF usually 1:50 for insulin sensitive (<50u) patients and 1:25 for insulin resistant patients
The CF can be estimated by taking the total daily insulin dose and dividing it into 1800 (the 1800 rule)
You also need to pick a target glucose level for the patient
(between 100 and 150) Walsh JA, Roberts R. Pumping Insulin 5th edition. 2011

Example of Determining the Correction Factor
• Used at meal time AND for unexpected hyperglycemia in between meals
• 21 year old female on insulin glargine
15 units at night and taking approximately 15 – 20 units a day in boluses with insulin glulisine
- (1800/35 units = 51)~ CF 1:50

[lakers]

Title:
 USE OF ULTRARAPID ACTING INSULIN

WIPO Patent Application WO/2015/148905
www.freepatentsonline.com/WO2015148905A1.html
Abstract:

Disclosed herein are improved methods of treating hyperglycemia with a combination of an ultrarapid acting insulin and insulin glargine comprising prandial administration of the ultrarapid insulin, and administration of a first dose of insulin glargine within 6 hours of waking for a day.

Inventors:

BOSS, Anders, Hasager (285 Cold Soil Road, Princeton, NJ, 08540, US)

[Former Mnkd CMO, now Sanofi's Senior Medical Director Diabetes and U.S. Medical Lead]

Anders Boss

Chief Medical Officer at MannKind Corporation

United StatesBiotechnology

Current Chief Medical Officer at MannKind Corporation

Past VP Medical Affairs at Rheologics, Sr Medical Director at Takeda Pharmaceuticals, Medical Director at Novo Nordisk

Education University of London, Københavns Universitet

www.linkedin.com/pub/dir/Anders/Boss
www.healthline.com/diabetesmine/six-things-know-starting-afrezza

PETRUCCI, Richard (917 Silvermine Road, New Canaan, CT, 06840, US)

Application Number:

US2015/022956

Publication Date:

10/01/2015

Filing Date:

03/27/2015

Claims:

What is claimed is:

1 . A method of treating higher than targeted pre-meal blood glucose comprising: regularly administering a split dose of an ultra rapid acting insulin formulation, the split dose including an initial dose taken at mealtime and a second dose of between 10% to 100% of the initial dosage taken 30 to 150 minutes after beginning a meal; wherein when pre-meal blood glucose for a next meal had been regularly greater than desired.

2. The method of claim 1 , wherein the second dose is taken 60-150 minutes after beginning a meal.

3. The method of claim 2, wherein the second dose is taken 90-150 minutes after beginning a meal.

4. The method of claim 1 , wherein said regularly greater than desired comprises pre-meal blood glucose levels of greater than 120 mg/dl for a majority of the pre-meal blood glucose tests within a given time period.

5. The method of claim 1 , wherein the pre-meal blood glucose is greater than 120 mg/dl.

6. The method of claim 4, wherein said regularly greater than desired comprises pre-meal blood glucose levels of greater than 140 mg/dl for a majority of the pre-meal blood glucose tests within a given time period.

7. The method of claim 1 , wherein the pre-meal blood glucose is greater than 140 mg/dl.

8. The method of claim 1 , wherein the pre-meal blood glucose is regularly greater than desired when at least three pre-meal blood glucose readings are taken within 10 days and are greater than 100 mg/dl.

9. The method of claim 8, wherein the pre-meal blood glucose is regularly greater than desired when at least three pre-meal blood glucose readings are taken within 5 days and are greater than 100 mg/dl .

10. A method of treating hyperglycemia comprising: administering a secondary dose of an ultra rapid acting insulin formulation 30 to 120 minutes after a mealtime dose comprising between 10% to 100% of an initial dose, wherein the secondary dose is titrated so that median blood glucose 1 to 2 hours after the secondary dose is less than 180 mg/dl.

1 1 . The method of claim 10 wherein the secondary dose is administered to a patient in which increasing the dosage of the mealtime dose produces an undesirably lesser, non-proportional reduction is blood glucose as compared to an unincreased mealtime dosage.

12. The method of any of the preceding claims wherein the ultra rapid acting insulin formulation comprises 3,6-di(succinyl-4-aminobutyl)-, 3,6-di(maleyl-4-aminobutyl)-, 3,6- di(glutaryl-4-aminobutyl)-, 3,6-di(malonyl-4-aminobutyl)-, 3,6-di(oxalyl-4-aminobutyl)-, or 3,6-di(fumaryl-4-aminobutyl)-2,5-diketopiperazine.

13. The method of any of the preceding claims wherein the ultra rapid acting insulin formulation comprises 3,6-di(fumaryl-4-aminobutyl)-2,5-diketopiperazine.

14. The method of any of the preceding claims wherein the ultra rapid acting insulin comprises human insulin.

15. The method of any of the preceding claims wherein administration is by inhalation.

16. The method of any of the preceding claims wherein administration is by pulmonary inhalation.

[dreamboatcruise]

Great to see Afrezza listed. Would be even better if there was a separate section on Afrezza dosing as the prandial instructions would seem to imply Afrezza cartridges need to come in smaller units.

[mssciguy]

thanks. sleep well

[factspls88]

There's that ultra-rapid designation again.  Is it possible that there has been approval of a label change for Afrezza - or is the presenter taking creative license with the terminology? 

[rrtzmd]

Dec 10, 2015 12:35:20 GMT -5 lakers said:

Three New Insulins Recently Added To
Our List Of Options*
Both approved by the FDA and now available for patients
1. U-300 glargine (Toujeo) a long acting basal insulin
2. U-100/200 degludec (Tresiba) a long acting basal insulin
3. Technosphere Inhaled insulin (Afrezza) an ultra rapid acting inhaled insulin

Prandial Dosing In Type 2 Diabetes
• Start with 4 to 5 units or 10% of the total basal dose, of a rapid acting analog or inhaled insulin
• Add 2 units every 3 days if median BS before the next meal or bedtime (only for the pre- dinner dose) until at goal (140 to 180mg/dl)
• Add 1 unit every day if the BS before the next meal or bedtime (only for the pre-dinner dose) until at goal (140 to 180 mg/dl)
• Reduce the dose by 2 units if patients has hypoglycemia below 70 mg/dl

tcoyd.org/PDF/2015-postp-santaclara-slides.pdf

Insulin Human (Afrezza)
Compared with other rapid-acting insulins:
• Peaks faster and offsets faster
• When added to basal insulin, equivalent A1C lowering • Lower postprandial blood glucose
• Less delayed hypoglycemia
Can be used in Type 1 diabetes in addition to a basal insulin (long acting insulin or basal rate via an insulin pump)
Can be used in Type 2 diabetes in addition to orals alone, orals and basal, or MDI regimens
Clin. Ther., 2014;Vol 36:Number 8: 1275-1289.

Prandial Dosing In Type 1
Insulin to Carbohydrate Ratio
Calculation: I:CHO
(Type 1 and Type 2 on MDI)
} Start with a ratio of 1:15 for insulin sensitive type 1 diabetics
} Start with a ratio of 1:10 for insulin resistant type 2 diabetics
} Formula: divide Total daily insulin dose into 500 } Example: 34 year old male with type 1 diabetes
currently on 25 units of glargine (Lantus) every night and 20 to 25 units of aspart (Novolog) each day: 500/50=10 So the initial Insulin to carb ratio is 1:10

Correction Factor (CF)
or Insulin Sensitivity Factor (ISP)
(Type 1 andn Type 2 on MDI)
Giving your patients a correction factor is a very practical tool whether they are on a pump or not
The CF is an estimate of how much the BS will drop with one unit of fast acting insulin
The CF usually 1:50 for insulin sensitive (<50u) patients and 1:25 for insulin resistant patients
The CF can be estimated by taking the total daily insulin dose and dividing it into 1800 (the 1800 rule)
You also need to pick a target glucose level for the patient
(between 100 and 150) Walsh JA, Roberts R. Pumping Insulin 5th edition. 2011

Example of Determining the Correction Factor
• Used at meal time AND for unexpected hyperglycemia in between meals
• 21 year old female on insulin glargine
15 units at night and taking approximately 15 – 20 units a day in boluses with insulin glulisine
- (1800/35 units = 51)~ CF 1:50

For those interested in details, the slides are based upon this article by Dr. Edelman:

Breath of Fresh Air? A Review of Inhaled Insulin

[rrtzmd]

Dec 10, 2015 22:30:34 GMT -5 factspls88 said:

There's that ultra-rapid designation again.  Is it possible that there has been approval of a label change for Afrezza - or is the presenter taking creative license with the terminology? 

No approval for label change from the FDA. Dr. Edelman simply refers to it in that manner. Also, MNKD was using that designation years ago as well -- e.g. this article:

Coverage of prandial insulin requirements by means of an ultra-rapid-acting inhaled insulin.

[mnkdfann]

Dec 10, 2015 22:30:34 GMT -5 factspls88 said:

There's that ultra-rapid designation again.  Is it possible that there has been approval of a label change for Afrezza - or is the presenter taking creative license with the terminology? 

The link to a 2012 paper below was just posted in another thread, and I noticed that the paper also used the ultra rapid description. So it seems the terminology goes back a ways.

www.ncbi.nlm.nih.gov/pubmed/22920801

EDIT: Or, to put it another way, what rrtzmd just said. :-)

[lakers]

Dosing protocol, CGM for a superiority trial design
Real-World Afrezza: Focus Group Feedback and Giving Inhaled Insulin a Second Try

Welcome back to another post in our periodic "Afrezza in the Real World" series, chronicling the real-life experiences of people with diabetes using the new Afrezza inhaled insulin.

You may remember that our own AmyT here at the 'Mine has been using Afrezza since March, and is still enjoying its quick action for bolus doses and between-meal BG corrections.

Anyone following me on social media may remember that I tried Afrezza myself in a brief trial-run back in September. Although I was impressed to see how quickly Afrezza could lower my blood sugar compared to how long it takes regular insulin to kick in, I ended up deciding it wasn't a long-term choice for me -- in part because I worry about the possible effects on the lungs that no one can foresee at this point, but also because of the lack of insurance coverage and cost aspects.

Real World AfrezzaAs always, YDMV (Your Diabetes May Vary), and we hear from many folks having very positive experiences with it.

Unfortunately, that may not be the case for much longer, as Sanofi is currently deciding how to proceed with this drug in the face of disappointing sales numbers for 2015. Afrezza's future is uncertain and Sanofi could potentially drop Afrezza from its production lineup at the start of 2016. If that happens, Mannkind would have to find a new partner to manufacture, market and sell Afrezza.

Whatever happens, many are enjoying the Afrezza experience in the meantime, and we're happy to continue sharing their various stories here as part of our #RealWorldAfrezza series.

Today, we hear from renowned endocrinologist and type 1 himself Dr. Jeremy Pettus in San Diego, CA, who's just recently decided to start using Afrezza again after a failed first try. Jeremy also works with the beloved Taking Control of Your Diabetes (TCOYD) conference series, and runs the We Are One Diabetes group for PWDs who work professionally in diabetes.

A Guest Post on Afrezza by Jeremy Pettus

I wanteJeremy Pettusd to write today about Afrezza. My tune on this med has changed slightly after Dr. Steve Edelman and I put on a very interesting focus group on a during the first weekend of December to discuss the medication. The purpose of the group was to learn how successful Afrezza users use Afrezza successfully (say that 10 times fast!) with the intent of designing a clinical trial around this info.

[Rumor of Sny dropping Afrezza doesn't match the intent of designing a clinical trial around this info. Label improvement was part of Sny road map all along. See Mnkd's previous slides if you can dig it up]


Some of the comments we heard during the focus group:

A big takeaway from this focus group meeting: There are people out there using this medication very well to achieve crazy-low A1Cs, like in the 5s, along with low rates of hypoglycemia. I mean these people got pissed when their BG was above 130! So how are they doing it?

Well, let me back up a second first and explain my first experience with Afrezza. Basically when I first took it, I took 4 units and then ate a sandwich. An hour or so later, my BG was over 250mg/dL, so I thought it didn’t work and never took it again.

Turns out my experience is somewhat common. The reason for this is that one unit of Afrezza is NOT equal to one unit of subcutaneous insulin. In fact, inhaling 4 units of Afrezza is closer to injecting 2.5 or 3 units. So basically, I dramatically under-dosed myself.

Now that I know that, I have been trying Afrezza for the last couple days, taking the right dose at the start of a meal or even 10 minutes into it and being slightly more aggressive. The really nice thing about the drug is that it works really, really fast but then totally hits the brakes.

Yesterday, I had a high of ~250 BG, took 8 units of Afrezza and my BG came screaming down with two down arrows on the CGM. I started to get nervous, but by like an hour into it, my BG totally flattened out without going low. So it truly is rapid-on and rapid-off. Yes, it takes some getting used to the new dosing regimen, inhaling something that can make you cough initially, and whipping out something that resembles a crack pipe in public always makes for some interesting reactions. But overall, it does fit an unmet need and has its place in our world.

You should have heard some of these comments from people in the focus group talking about their control.

One guy was “complaining” that the high alarm on the Dexcom should let you go lower than 120mg/dL... wow! Can you imagine setting your HIGH alarm at 120?! He was saying this because he really was achieving perfect control, mostly by controlling that annoying post-meal spike. If you can control that, you'll never again have to deal with the all-too-common scenario of correcting for a high post-meal BG which makes you go low, then raiding the fridge, eat everything in sight and yelling at your significant other “don’t tell me what to eat!”... And then going high again, having to rage bolus 20 units of insulin, and then going low again and repeating. I call it being on the rollercoaster, but instead of being fun like an actual rollercoaster, it just sucks.

Afrezza seems to take care of this rollercoaster effect (see also glucoastering) very well.

Advertisement

I mention this also because there are murmurings about the drug being discontinued in the near future because it is not selling well. I think this mostly comes from providers (not patients) being uncomfortable with the drug given all the things I mentioned above that are new. So if you haven’t tried it, or the doctors haven't offered or discussed it with patients, time might be running out!

I took Afrezza for a couple days on samples, but then had a lag and haven't picked up my script, so I don't have any hard data to look at as to how well it did for me.

Overall, I think the point is that there's a learning curve. Most type 1s have been on subcutaneous injections for a long time -- decades even, so this is kinda like starting over again and relearning how the drug effects you and your blood sugars. I'm hoping to learn quickly (using my CGM) how to dose Afrezza and see if I become a full-time convert.

Thanks for sharing your POV, Jeremy. Like you, we are nervous about the inhaled insulin's future, and hope to see it stick around as a valuable tool for us PWDs.
Click on
www.healthline.com/diabetesmine/afrezza-focus-group-feedback
To see picx of 13-person focus group in SD incl. Sam, Eric, Dr Edelman, et al

[cjc04]

Thanks Lakers,,,, there's a lot of good stuff there, but it's also a bit alarming. The acceptance of Afrezza seems to be much, much slower than the worst case that I thought.

Your thoughts?

[bradleysbest]

Can't wait forever for commercials to begin. There will be lag time due to appts, insurance approval etc... So lets get this party started!

[mnholdem]

Comparing the inhaler to a crack pipe showed unabashed bias, in my opinion. Bias is revealed because no comparison is made of the stigma associated with "pulling out" a needle/pen. Why wasn't this author required to sign a NDA like everyone else? This piece is clearly an attempt to persuade readers that Afrezza belongs in a "niche" category.

[mssciguy]

Dec 15, 2015 15:03:12 GMT -5 mnholdem said:

Comparing the inhaler to a crack pipe showed unabashed bias, in my opinion. Bias is revealed because no comparison is made of the stigma associated with "pulling out" a needle/pen. Why wasn't this author required to sign a NDA like everyone else? This piece is clearly an attempt to persuade readers that Afrezza belongs in a "niche" category.

If it looked like a crack pipe, Wu Tang fan Shrkeli would be all over it!

[cjc04]

Dec 15, 2015 15:03:12 GMT -5 mnholdem said:

Comparing the inhaler to a crack pipe showed unabashed bias, in my opinion. Bias is revealed because no comparison is made of the stigma associated with "pulling out" a needle/pen. Why wasn't this author required to sign a NDA like everyone else? This piece is clearly an attempt to persuade readers that Afrezza belongs in a "niche" category.

That was my exact impression.... That it will stumble along slowly gaining a niche crowd.

[vissertrades]

Novel, clever, discrete, simple to use, and disposable were all terms I've heard used previously. Now it's a crack pipe? Perhaps this IS something Mannkind should defend?