Afrezza® INHALE-1 Study in Pediatrics (INHALE-1)

[akemp3000]

If the results of this study show non-inferior A1C but daily TIR superiority with fewer hypos, this should be the proverbial "shot heard round the world" among endos and global diabetics. It's hard to imagine why any diabetic that can inhale would choose to start or continue with prandial shots. It's also hard to imagine why any endo knowing these results would recommend anything else.

If so, with Billions at stake annually, this should finally force one or more of the BP giants to make a play for Mannkind. You can bet they all already know the anticipated outcome that most here expect to see. If true, IMO it's likely one of the companies will make a play prior to the results being announced at the end of the study. Such a play would be expensive but waiting would be risky and more expensive. It's not hard to imagine one of the BP giants taking control and launching a big ad campaign in an attempt to dominate the competition. The next year or two for this little company is looking better than ever.

[Deleted]

Jul 24, 2021 6:35:25 GMT -5 akemp3000 said:

If the results of this study show non-inferior A1C but daily TIR superiority with fewer hypos, this should be the proverbial "shot heard round the world" among endos and global diabetics. It's hard to imagine why any diabetic that can inhale would choose to start or continue with prandial shots. It's also hard to imagine why any endo knowing these results would recommend anything else.

If so, with Billions at stake annually, this should finally force one or more of the BP giants to make a play for Mannkind. You can bet they all already know the anticipated outcome that most here expect to see. If true, IMO it's likely one of the companies will make a play prior to the results being announced at the end of the study. Such a play would be expensive but waiting would be risky and more expensive. It's not hard to imagine one of the BP giants taking control and launching a big ad campaign in an attempt to dominate the competition. The next year or two for this little company is looking better than ever.

You may be right but we have to wait 3 years for the final results.  Apparently the FDA feels it will take a long time (~12+ mos.) to recruit kids.     

[hellodolly]

Jul 23, 2021 11:18:57 GMT -5 mango said:

Looking at the outcome measures and the fact we are using CGMs—this clinical trial is set up to be absolutely monumental and game changing.



I truly believe Afrezza will prove to be the superior mealtime insulin therapy once and for all with this clinical trial.

I remember the clamoring for a PEDS trial a few years back.  All I can say is thankfully, it didn't happen. The stars have all aligned, in that:

1. This trial will use CGMs, under adult supervision
2. Users have learned that TIR is a key benefit for Afrezza users, a key metric for patients regardless of the trial design for primary or secondary...or, as in this trial "other outcome measures"
3. The anecdotal feedback on social media by users regarding what works and what doesn't work, i.e; overcoming the initial cough, angle of trajectory with the device, best time to dose, dose adjustments, etc. are accessible with some simple internet searches

None of this would have been possible years ago.   Now, there are sources and a cache of information available that wasn't available years ago. 

[sayhey24]

Jul 23, 2021 19:31:59 GMT -5 cedafuntennis said:

Jul 23, 2021 18:40:53 GMT -5 sayhey24 said:

Well - here we go again, trying to show how afrezza over a long period of time is better than an RAA. Its not.
Primary Outcome Measures :
Change in HbA1c After 26 Weeks [ Time Frame: 26 weeks ]

They better be monitoring closely and properly second and third dosing or this is going to turn out to Affinty-1 all over again.

There is nothing better than repeated hypos to lower A1c. The Primary outcome should be non-inferior in A1C and fewer hypos.

With TIR superiority

Don't get to excited about TIR in this study.  First, its an  "Other Outcome".  Second, its taking TIR over a 24hr period.  Third, its using 180 mg/dl as the upper bound.  
The TIR should just be looking from breakfast until 3hrs after dinner so maybe 8am until 10pm.  TIR during sleeping is strictly a basal and any left over RAA thing.  Afrezza should be out of the system by 10pm.

We also know 140mg/dl should be the upper bound for TIR not the 180 mg/dl.  MNKD should have split the distance and used 160mg/dl. which would make it much harder for the RAAs.

The good news is at least they are getting the study done. I think Sports could round them up 300 kids in short order.  Maybe they should be calling her. 

[letitride]

3.5 to 4.5 years for a 1 year trial is this normal for clinical trials +/- 1 year ?

[wsulylecoug]

As long as participants aren’t handcuffed by protocols that ultimately favor RAA and allow flexibility in timing, amount and follow-ups as needed. I don’t associate FDA trials with flexibility but I’m trusting MC fought for the best design to benefit Afrezza users and the trial outcome. Past comments suggest the FDA was willing to work with MNKD but then again I wouldn’t expect too much bad-mouthing during the trial design process.

160 might not have been an option for TIR upper bound. I assume there was some back and forth for some trial details that required some give and take.

It’s been mentioned previously, but once the trial gets the green light, it appears the expectation is that recruitment will take a long time. Typically Clinicaltrials.gov also lists recruitment sites and maybe there aren’t very many. Participants also need to be using basal with mealtime MDI. Does that include pumps? If not, the recruiting pool shrinks again. At first glance it doesn’t seem like it should take long to fill but time will tell. Those dates can be adjusted on the website with a few clicks of a mouse.

[sportsrancho]

[sportsrancho]

Diabetic summer camps would be a good place to recruit.
I would send some of the reps from Mannkind to give a talk at camps around the country.


beyondtype1.org/diabetes-camp/

[olderteampt]

Here is an idea on how to get the Peds trial started earlier:

If MNKD would partner with a CGM company the CMG company could offer a free CGM machine to every child that signed up for the Peds study. How many parents would jump at the opportunity to get a free CGM machine for their child for signing up for the study? I think they could sign up 300 children in 1 month or less. That would cost the CGM company the cost of 300 machines which they could write off as a sales expense. The reason they would do this is because they could end up with a CGM client for life if the child has a great experience with Afrezza and the CGM. Next, through word of mouth how many new customers could that new child customer refer to lets say DXCM over the course of their lives? MNKD could even offer to split a percentage of the cost of those 300 machines to the CGM manufacturer to lower their initial costs. Next, both companies would be letting the public know how they are committed to help humanity through the advertising of such a promotion. The theme of the promotion could be XYZ company is helping children with Diabetes with early intervention before they develop the horrific side-effects of such an ugly disease. Let me repeat, "XYZ company is promoting early intervention!" If their competition is not who do you think will come out as the long term winner?

[prcgorman2]

Matt, agedhippie, and at least one newly minted doctor, all provided good posts on importance of a well-designed “large trial”. Is this that trial? I wonder if we will be seeing another trial for adults. Either way, I couldn’t be more pleased to hear the news although I have the same negative opinion as others about the overall length of the trial. I’m not qualified to assess the trial design, but I hope that more than anything, the pediatric trial demonstrates the safety of Afrezza as compared to RAA. We all know it’s safer. My wife lost a 20-something cousin some years back to a hypo so it’s the one aspect of Afrezza I feel most strongly needs to be emphasized. As I understand it, concern for safety is the fundamental reason for reluctance to put T2 PWDs on insulin. So instead they are prescribed drugs to squeeze the pancreas with vice-grips and push the liver and kidneys to unusual efforts. Barbaric.

[lennymnkd]

The CGM IS THE LIE DETECTOR TEST ! and it's in our favor ... as simple as that .

[sayhey24]

Jul 24, 2021 9:38:09 GMT -5 wsulylecoug said:

As long as participants aren’t handcuffed by protocols that ultimately favor RAA and allow flexibility in timing, amount and follow-ups as needed. I don’t associate FDA trials with flexibility but I’m trusting MC fought for the best design to benefit Afrezza users and the trial outcome. Past comments suggest the FDA was willing to work with MNKD but then again I wouldn’t expect too much bad-mouthing during the trial design process.

160 might not have been an option for TIR upper bound. I assume there was some back and forth for some trial details that required some give and take.

It’s been mentioned previously, but once the trial gets the green light, it appears the expectation is that recruitment will take a long time. Typically Clinicaltrials.gov also lists recruitment sites and maybe there aren’t very many. Participants also need to be using basal with mealtime MDI. Does that include pumps? If not, the recruiting pool shrinks again. At first glance it doesn’t seem like it should take long to fill but time will tell. Those dates can be adjusted on the website with a few clicks of a mouse.

The study says "RAA injection combined with a basal insulin".  If they are using a pump they are not using a basal. 

The 180 mg/dl is nearly an A1C of 8.  An A1c of 160 is still over 7, but its a lot better than an 8.  Now, the 180 is the safe historical number to target because of the fear of hypoglycemia.  The historical treatment approach is its much better to have the PWD'sBG high and have vascular degeneration which takes years than to have the PWD go low and get a severe hypo.   I too agree with this but a study like this needs to showcase afrezza's benefits.

Afrezza is a game changer and this study protocol is just not designed to bring out the best in afrezza.  The next time I see Mike I will probably give him my opinion.  I am sure he will have reasons like the FDA is comfortable with 180 and they may not have accepted 160.  He will also probably say the FDA is not yet ready to drop A1C as the primary outcome when evaluating diabetes meds.  He may also say going for 160 mg/dl may limit the number of moms who want to let their kids participate in this study if they are in the RAA arm.

As far as getting kids, Sports already had a great suggestion in another post about going to the diabetes summer camps.  

[neil36]

Jul 24, 2021 10:23:35 GMT -5 sportsrancho said:

Diabetic summer camps would be a good place to recruit.
I would send some of the reps from Mannkind to give a talk at camps around the country.


beyondtype1.org/diabetes-camp/

I got interested in pediatric diabetes primarily due to two T1D nephews. It dominates their entire lives.

I think diabetes summer camps would be brilliant if set up correctly

[mango]

Jul 23, 2021 18:40:53 GMT -5 sayhey24 said:

Well - here we go again, trying to show how afrezza over a long period of time is better than an RAA. Its not.
Primary Outcome Measures :
Change in HbA1c After 26 Weeks [ Time Frame: 26 weeks ]

They better be monitoring closely and properly second and third dosing or this is going to turn out to Affinty-1 all over again.

There is nothing better than repeated hypos to lower A1c. The Primary outcome should be non-inferior in A1C and fewer hypos.

It looks like the participants will be monitored via CGMs? I haven’t looked at the protocol closely, but if that’s the case, we will know the percentages of hypos they get from the RAAs and can thus show that it was an increase in frequency and duration of RAAs hypos that causes the often seen dramatic decline in A1c.

The HbA1c hypothesis is false and it’s time to put an end to using it for assessing glucose homeostasis and managing diabetes from it.

[peppy]

Jul 26, 2021 10:32:43 GMT -5 mango said:

Jul 23, 2021 18:40:53 GMT -5 sayhey24 said:

Well - here we go again, trying to show how afrezza over a long period of time is better than an RAA. Its not.
Primary Outcome Measures :
Change in HbA1c After 26 Weeks [ Time Frame: 26 weeks ]

They better be monitoring closely and properly second and third dosing or this is going to turn out to Affinty-1 all over again.

There is nothing better than repeated hypos to lower A1c. The Primary outcome should be non-inferior in A1C and fewer hypos.

It looks like the participants will be monitored via CGMs? I haven’t looked at the protocol closely, but if that’s the case, we will know the percentages of hypos they get from the RAAs and can thus show that it was an increase in frequency and duration of RAAs hypos that causes the often seen dramatic decline in A1c.

The HbA1c hypothesis is false and it’s time to put an end to using it for assessing glucose homeostasis and managing diabetes from it.

I AGREE WITH YOU,
however,
What are the chances the industry will throw away its greatest sales tool?

It is the gateway tool. One number and the patient can be reprimanded by the supreme white coat and be put into the system.
Makes commercial messages unnecessary.

Alpha-glucosidase inhibitors

These medications help your body break down starchy foods and table sugar. This effect lowers your blood sugar levels.

For the best results, you should take these drugs before meals. These drugs include:

acarbose (Precose)
miglitol (Glyset)
Biguanides

Biguanides decrease how much sugar your liver makes. They decrease how much sugar your intestines absorb, make your body more sensitive to insulin, and help your muscles absorb glucose.

The most common biguanide is metformin (Glucophage, Metformin Hydrochloride ER, Glumetza, Riomet, Fortamet).

Metformin can also be combined with other drugs for type 2 diabetes. It’s an ingredient in the following medications:

metformin-alogliptin (Kazano)
metformin-canagliflozin (Invokamet)
metformin-dapagliflozin (Xigduo XR)
metformin-empagliflozin (Synjardy)
metformin-glipizide
metformin-glyburide (Glucovance)
metformin-linagliptin (Jentadueto)
metformin-pioglitazone (Actoplus)
metformin-repaglinide (PrandiMet)
metformin-rosiglitazone (Avandamet)
metformin-saxagliptin (Kombiglyze XR)
metformin-sitagliptin (Janumet)
Dopamine agonist

Bromocriptine (Cycloset) is a dopamine agonist.

It’s not known exactly how this drug works to treat type 2 diabetes. It may affect rhythms in your body and prevent insulin resistance.

Dipeptidyl peptidase-4 (DPP-4) inhibitors

DPP-4 inhibitors help the body continue to make insulin. They work by reducing blood sugar without causing hypoglycemia (low blood sugar).

These drugs can also help the pancreas make more insulin. These drugs include:

alogliptin (Nesina)
alogliptin-metformin (Kazano)
alogliptin-pioglitazone (Oseni)
linagliptin (Tradjenta)
linagliptin-empagliflozin (Glyxambi)
linagliptin-metformin (Jentadueto)
saxagliptin (Onglyza)
saxagliptin-metformin (Kombiglyze XR)
sitagliptin (Januvia)
sitagliptin-metformin (Janumet and Janumet XR)
sitagliptin and simvastatin (Juvisync)
Glucagon-like peptide-1 receptor agonists (GLP-1 receptor agonists)

These drugs are similar to the natural hormone called incretin.

They increase B-cell growth and how much insulin your body uses. They decrease your appetite and how much glucagon your body uses. They also slow stomach emptying.

These are all important actions for people with diabetes.

For some people, atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease may predominate over their diabetes. In these cases, the American Diabetes Association (ADA) recommends certain GLP-1 receptor agonists as part of an antihyperglycemic treatment regimen.

These drugs include:

albiglutide (Tanzeum)
dulaglutide (Trulicity)
exenatide (Byetta)
exenatide extended-release (Bydureon)
liraglutide (Victoza)
semaglutide (Ozempic)
Meglitinides

These medications help your body release insulin. However, in some cases, they may lower your blood sugar too much.

These drugs aren’t for everyone. They include:

nateglinide (Starlix)
repaglinide (Prandin)
repaglinide-metformin (Prandimet)
Sodium-glucose transporter (SGLT) 2 inhibitors

Sodium-glucose transporter (SGLT) 2 inhibitors work by preventing the kidneys from holding on to glucose. Instead, your body gets rid of the glucose through your urine.

In cases where atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease predominate, the ADA recommends SGLT2 inhibitors as a possible treatment option.

dapagliflozin (Farxiga)
dapagliflozin-metformin (Xigduo XR)
canagliflozin (Invokana)
canagliflozin-metformin (Invokamet)
empagliflozin (Jardiance)
empagliflozin-linagliptin (Glyxambi)
empagliflozin-metformin (Synjardy)
ertugliflozin (Steglatro)
Sulfonylureas

These are among the oldest diabetes drugs still used today. They work by stimulating the pancreas with the help of beta cells. This causes your body to make more insulin.

These drugs include:

glimepiride (Amaryl)
glimepiride-pioglitazone (Duetact)
glimepiride-rosiglitazone (Avandaryl)
gliclazide
glipizide (Glucotrol)
glipizide-metformin (Metaglip)
glyburide (DiaBeta, Glynase, Micronase)
glyburide-metformin (Glucovance)
chlorpropamide (Diabinese)
tolazamide (Tolinase)
tolbutamide (Orinase, Tol-Tab)
Thiazolidinediones

Thiazolidinediones work by decreasing glucose in your liver. They also help your fat cells use insulin better.

These drugs come with an increased risk of heart disease. If your doctor gives you one of these drugs, they’ll watch your heart function during treatment.

Options include:

rosiglitazone (Avandia)
rosiglitazone-glimepiride (Avandaryl)
rosiglitazone-metformin (Amaryl M)
pioglitazone (Actos)
pioglitazone-alogliptin (Oseni)
pioglitazone-glimepiride (Duetact)
pioglitazone-metformin (Actoplus Met, Actoplus Met XR)