Standards of Care in Diabetes—2023

[kite]

diabetesjournals.org/care/issue/46/Supplement_1

[agedhippie]

I think they are trolling Sayhey.

From the revisions section discussing the intensification sequence for Type 2:

Information was added to address considerations for a GLP-1 receptor agonist prior to prandial insulin to further address prandial control and to minimize the risks of hypoglycemia and weight gain associated with insulin therapy.

What they are saying is that after basal the patient should go to GLP-1 before they go to mealtime insulin if they are not already on a GLP-1. Effectively they have inserted an extra step.

[sayhey24]

What can I say. This stuff makes my head explode. I saw this a few weeks back and wasn't going to even comment on it.

I wonder what would happen if MNKD got busy and started properly marketing afrezza. Can't we at least get the story out there that getting severe hypoglycemia with afrezza is really really hard if you are not taking a basal insulin? Just when you have hope that maybe Mike and team have been doing something with the ADA like some lobbying, nope reality hits again. This is so frustrating. I guess Mike is too busy talking with some "thought leaders" like when he was in Spain.

For God's sake we have the best "oral" glycemic control medication and getting hypos with it is not an issue. Weight gain is not an issue. T1's are saying its working really well when taking with the GLP1 for weight loss. This is what we get - good grief. Well, there is always next year.

[mango]

The SoC is King and until MannKind does the proper clinical trials to change the SoC, which is unfavorable to Afrezza and basically dismisses it, it will be very slow growth. Peds will certainly add new growth and most likely Afrezza-For-Life-Users, but again, unless the Peds clinical trial produces results that change the SoC making Afrezza significantly more favorable and recommended over injectable insulins then little is going to change, short of a revolution (which is also possible but unlikely).

MannKind should invest the money in some large scale, long term clinical trials designed to change the SoC for long term company success, better shareholder value, advancing medicine and enabling better outcomes.

[akemp3000]

Mannkind needs a very strong BP partner to even think about changing the SOC. MC has said from the beginning that a partner was desired. Yes, it is frustrating.

[mango]

Dec 20, 2022 16:40:15 GMT -5 akemp3000 said:

Mannkind needs a very strong BP partner to even think about changing the SOC. MC has said from the beginning that a partner was desired. Yes, it is frustrating.

Why don’t we have a BP partner yet?

[peppy]

Dec 20, 2022 17:18:25 GMT -5 mango said:

Dec 20, 2022 16:40:15 GMT -5 akemp3000 said:

Mannkind needs a very strong BP partner to even think about changing the SOC. MC has said from the beginning that a partner was desired. Yes, it is frustrating.

Why don’t we have a BP partner yet?

Sanofi figured out with a non inferior label, they couldn't make money with Afrezza the way the system is now set up.

You know the system, The pharmacy price involves a rebate to the manufacturer. 
UTHR included that in the agreement with MNKD. Pricing and reinbursement including rebates, (or kickbacks. rebates....)

I do not believe Sanofi was paying rebates to the pharmacy purchasing manager. You want to play you have to pay.
Or Catch and Kill, since rebates were never set up.

mango, what is your take, why doesn't MNKD have a partner for Afrezza?

[Thundersnow]

Dec 20, 2022 16:31:27 GMT -5 mango said:

The SoC is King and until MannKind does the proper clinical trials to change the SoC, which is unfavorable to Afrezza and basically dismisses it, it will be very slow growth. Peds will certainly add new growth and most likely Afrezza-For-Life-Users, but again, unless the Peds clinical trial produces results that change the SoC making Afrezza significantly more favorable and recommended over injectable insulins then little is going to change, short of a revolution (which is also possible but unlikely).

MannKind should invest the money in some large scale, long term clinical trials designed to change the SoC for long term company success, better shareholder value, advancing medicine and enabling better outcomes.

I believe the Pediatric Trial will set the stage for MNKD to change the SOC.   If you look at the Primary and Secondary Outcomes it's massive. 
There's are over 25 Outcomes and if you remember the Trial was delayed for about 30 months.  Mike wants this to be the trial that changes everything for Afrezza.  And what better subject than KIDS.   


Primary Outcome Measures :
Change in HbA1c [ Time Frame: 26 weeks ]
Change in HbA1c from baseline to Week 26, for noninferiority assessment


Secondary Outcome Measures :
Change in HbA1c [ Time Frame: 26 weeks ]
Change in HbA1c from baseline to Week 26, for superiority assessment

Change in Fasting Plasma Glucose (FPG) [ Time Frame: 26 weeks ]
Change in FPG from baseline to Week 26, for superiority assessment

Event rate of pooled level 2 and level 3 hypoglycemia [ Time Frame: 26 weeks ]
Event rate of pooled level 2 and level 3 hypoglycemia (self-monitored blood glucose [SMBG] <54 mg/dL and/or severe hypoglycemic events) during the 26-week randomized treatment period, for superiority assessment


Other Outcome Measures:
Event rate of level 1 hypoglycemia (SMBG <70 mg/dL) [ Time Frame: 26 weeks ]
Event rate of level 1 hypoglycemia during the 26-week randomized treatment period

Change in percent Time In Range (glucose 70 - 180 mg/dL) [ Time Frame: 26 weeks ]
Change in percent Time In Range from baseline to Week 26, using Continuous Glucose Monitoring (CGM)-derived data collected over the preceding 30 days for the 24-hour, daytime and nocturnal time periods

Change in percent time with glucose <54 mg/dL [ Time Frame: 26 weeks ]
Change in percent time with glucose <54 mg/dL from baseline to Week 26, using CGM-derived data collected over the preceding 30 days for the 24-hour, daytime and nocturnal time periods

Change in percent Time Below Range (glucose <70 mg/dL) [ Time Frame: 26 weeks ]
Change in percent Time Below Range from baseline to Week 26, using CGM-derived data collected over the preceding 30 days for the 24-hour, daytime and nocturnal time periods

Change in percent Time Above Range (glucose >180 mg/dL) [ Time Frame: 26 weeks ]
Change in percent Time Above Range from baseline to Week 26, using CGM-derived data collected over the preceding 30 days for the 24-hour, daytime and nocturnal time periods

Percentage of subjects with HbA1c <7.0% [ Time Frame: At Week 26 ]
Percentage of subjects with HbA1c <7.0% at Week 26

Score of Diabetes Treatment Satisfaction Questionnaire (DTSQ) Change (c)-Teen [ Time Frame: At Week 26 ]
Score of DTSQ(c)-Teen at Week 26 in the Afrezza group (score ranges from -24 to 24, with higher score means greater satisfaction)

Score of Diabetes Treatment Satisfaction Questionnaire (DTSQ) Change (c)-Parent [ Time Frame: At Week 26 ]
Score of DTSQ(c)-Parent at Week 26 in the Afrezza group (score ranges from -30 to 30, with higher score means greater satisfaction)

Change in scores of DTSQ Status (s)-Teen [ Time Frame: 26 weeks ]
Change in scores of DTSQ(s)-Teen from baseline to Week 26 (change in score ranges from -48 to 48, with higher score means greater satisfaction)

Change in scores of DTSQ Status (s)-Parent [ Time Frame: 26 weeks ]
Change in scores of DTSQ(s)-Parent from baseline to Week 26 (change in scores ranges from -60 to 60, with higher score means greater satisfaction)

Change in HbA1c [ Time Frame: 52 weeks (and 26 weeks if required) ]
Change in HbA1c from baseline to Week 52 (and change from Week 26 to Week 52 if required) in subjects who switch from treatment with RAA injections to Afrezza at Week 26

Change in FPG [ Time Frame: 52 weeks (and 26 weeks if required) ]
Change in FPG from baseline to Week 52 (and change from Week 26 to Week 52 if required) in subjects who switch from treatment with RAA injections to Afrezza at Week 26

Change in percent Time In Range, Time Below Range and Time Above Range [ Time Frame: 52 weeks (and 26 weeks if required) ]
Change in percent Time In Range, Time Below Range and Time Above Range from baseline to Week 52 (and change from Week 26 to Week 52 if required) in subjects who switch from treatment with RAA injections to Afrezza at Week 26; using CGM-derived data collected over the preceding 30 days for the 24-hour, daytime, and nocturnal periods

Change in HbA1c [ Time Frame: 52 weeks ]
Change in HbA1c from baseline to Week 52 in subjects who receive Afrezza in both the randomized treatment period and the treatment extension

Change in FPG [ Time Frame: 52 weeks ]
Change in FPG from baseline to Week 52 in subjects who receive Afrezza in both the randomized treatment period and the treatment extension

Change in percent Time In Range, Time Below Range and Time Above Range [ Time Frame: 52 weeks ]
Change in percent Time In Range, Time Below Range and Time Above Range from baseline to Week 52 in subjects who receive Afrezza in both the randomized treatment period and the treatment extension; using CGM-derived data collected over the preceding 30 days for the 24-hour, daytime, and nocturnal periods

Score of DTSQ(c)-Teen at Week 52 [ Time Frame: At Week 52 ]
Score of DTSQ(c)-Teen at Week 52 (after 6 months of Afrezza treatment) in subjects who switch from RAA injections to Afrezza (score ranges from -24 to 24, with higher score means greater satisfaction)

Score of DTSQ(c)-Parent at Week 52 [ Time Frame: At Week 52 ]
Score of DTSQ(c)-Parent at Week 52 (after 6 months of Afrezza treatment) in subjects who switch from RAA injections to Afrezza (score ranges from -30 to 30, with higher score means greater satisfaction)

Change in scores of DTSQ(s)-Teen [ Time Frame: 52 weeks ]
Change in scores of DTSQ(s)-Teen from baseline to Week 52 (changes in score ranges from -48 to 48, with higher score means greater satisfaction)

Change in scores of DTSQ(s)-Parent [ Time Frame: 52 weeks ]
Change in scores of DTSQ(s)-Parent from baseline to Week 52 (change in scores ranges from -60 to 60, with higher score means greater satisfaction)

Event rates of hypoglycemic events [ Time Frame: 52 weeks ]
Event rates and incidence of total, nocturnal, and severe hypoglycemic events from baseline to Week 52

Incidence of hypoglycemic events [ Time Frame: 52 weeks ]
Incidence of total, nocturnal, and severe hypoglycemic events from baseline to Week 52

Incidence and severity of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: 52 weeks ]
Incidence and severity of TEAEs and SAEs from baseline to Week 52

Incidence and severity of Adverse Events of Special Interest (AESIs) [ Time Frame: 52 weeks ]
Incidence and severity of AESIs (i.e., acute bronchospasm, clinically relevant decline in pulmonary function, hypersensitivity reactions [including anaphylaxis], asthma symptoms or exacerbations [including use of reliever or controller medications and hospitalization], and diabetic ketoacidosis [DKA]) as well as the number of subjects with AESIs and number of individual events from baseline to Week 52

Change in percent predicted Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: 56 weeks ]
Change from baseline to Weeks 13, 26, 39, 52, and 56 in percent predicted FEV1

[sayhey24]

Dec 20, 2022 17:40:47 GMT -5 peppy said:

Dec 20, 2022 17:18:25 GMT -5 mango said:

Why don’t we have a BP partner yet?

Sanofi figured out with a non inferior label, they couldn't make money with Afrezza the way the system is now set up.

You know the system, The pharmacy price involves a rebate to the manufacturer. 
UTHR included that in the agreement with MNKD. Pricing and reinbursement including rebates, (or kickbacks. rebates....)

I do not believe Sanofi was paying rebates to the pharmacy purchasing manager. You want to play you have to pay.
Or Catch and Kill, since rebates were never set up.

mango , what is your take, why doesn't MNKD have a partner for Afrezza?



Peppy - Sanofi licensed afrezza to target the T2 community.  The words on the label in the T2 section say the following

"At Week 24, treatment with AFREZZA plus OADs provided a mean reduction in HbA1c that was statistically significantly greater compared to the HbA1c reduction observed in the placebo group"  The placebo group continued to take their OADs but took Technosphere powder with no insulin.

In other words the label says afrezza provided superior HbA1c reduction when added to any of the anti-glycemics including the DDP4 Januvia.  The GLP1s were not available yet to include in the trial.

Sanofi never tried.  Sanofi did NOTHING except tell Al they could not sell it because the doctors did not have spirometers.  Come on every GP has a spirometer and this was total BS.  As soon as Brandicourt showed up he shut it down.  He was going to do whatever he could to stop afrezza.  Why is the big question.  Many say it was because of Toujero but and its a BIG but, Toujero was targeted at the T1 market and afrezza was targeting the T2s.  They planned to market to the PCP and GPs not the endos with afrezza.  This was the plan Sanofi had before Brandicourt.  They also knew Tresiba was going to eat Toujero's lunch and afrezza was the long-term play.

Being Tuesday night I have taken out the tin foil hat and put it on.  I think Brandicourt was in cahoots with the "industry".  I have no proof.  I just have a feeling.  It was way too weird.  Sanofi was gearing up for follow-up studies before Brandicourt arrived.  Now since the tin foil hat is still on I also think they got to Dave Kendall before the Mounjaro release to get him to stop any efforts of getting afrezza better representation in the SoC.   Again, no proof and I don't know Kendall.  All I know is every time I try to get an answer all I get is crickets.  Damn, he said this was the easiest job he every had and then poof - gone over night.  Then he goes and gets a consulting job.  Whats that about?

Peppy - the last thing the industry wants is for afrezza to succeed.  It would totally disrupt a $40B industry. Thats why MNKD does not have a partner. For the last 3 years we have seen even Mike is gun shy going after the T2 market.  I think he used the words "Shelved for the T2s". The partner MNKD needs is an outsider with lots and lots of money and stainless steel balls who is willing to blow up this industry.  What would have happened to Mounjaro in the T2 space if Dave Kendall kept going and afrezza showed superior A1c reduction to the GLP1s before Mounjaro was released?  Afrezza was not in any of the studies Mounjaro used.  Then what, Mounjaro has to go up against afrezza and losses?  Sure it is going to show great weight reduction while everyone is vomiting but its not going to beat afrezza on post prandial control and long term A1c control.

[hopingandwilling]

Wow! Reading UTHR's contract with MannKind reveals that what they have stated in this contract is NON-BINDING. In legal parlance, MannKind has no legal recourse to challenge anything that UTHR does regarding the product. It appears to be no guarantees of minimum orders of the product and any guarantee of manufacturing expenses that will be reimbursed. Such a contract isn't a problem as long as the products are being adopted and generating a revenue stream.

[sportsrancho]

Sayhey…. another weird thing SNY did was they flew all the early adapters, Sam, Eric, etc. down to Del Mar so that they could all meet there and they could give their testimonies, a week or a month after that, ( can’t remember) they dumped our ass …what in the world was that all about. I saw the plane tickets. They had them all sign NDA’s.

[mango]

Dec 20, 2022 22:07:06 GMT -5 sportsrancho said:

Sayhey…. another weird thing SNY did was they flew all the early adapters, Sam, Eric, etc. down to Del Mar so that they could all meet there and they could give their testimonies, a week or a month after that, ( can’t remember) they dumped our ass …what in the world was that all about. I saw the plane tickets. They had them all sign NDA’s.

It would interesting to have Sam disclose the details of that meeting. Perhaps someone can reach out to him and investigate.

[akemp3000]

That could certainly be interesting. Hopefully the NDAs had an expiration time frame. Even if Sam can't disclose details of the meeting it would still be interesting to hear his and Eric's current perspective on Afrezza.

[Thundersnow]

Dec 26, 2022 9:59:24 GMT -5 akemp3000 said:

That could certainly be interesting. Hopefully the NDAs had an expiration time frame. Even if Sam can't disclose details of the meeting it would still be interesting to hear his and Eric's current perspective on Afrezza.

I wonder if that's the reason why they have CLAMMED UP.   They were the 2 most outspoken people on Afrezza.  Wonder if they were on SNY's Social Media payroll?

[akemp3000]

After learning about the Twitter Files 9 released on Christmas Eve, anything's possible including a drug company possibly manipulating competitive spokespersons. No conspiracy theories though as far too many are turning out to be true. Hopefully we'll hear from Sam and Eric.