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Post by agedhippie on Jul 30, 2018 10:43:40 GMT -5
" Starting in 2018, the ADA will update the Standards of Care even more frequently online should the Professional Practice Committee de- termine that new evidence or regulatory changes merit immediate incorporation into the Standards of Care. In addition, the Standards of Care will now become the ADA’s sole source of clinical practice recommendations, superseding all prior position and scientific statements." Let's see how morally and ethically compelled they are to do so...and when. They will do it, but not without high grade trial data. They have their processes for what justifies updates and those are unchanged, just more timely. |
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Post by morgieporgie on Jul 30, 2018 16:40:26 GMT -5
sayhey would know, but I believe that is true, also people were not taking enough units halfway into the meal the very first time. A lot of times if you do that you do not need a second dose. Just depends... All the dosing information is in the lost studies. Dr. Kendall is in the process of verifying that all the info still holds true. I think he mentioned at the Investors conference he is currently working on dosing.
As Sports said a major problem is under-dosing. We saw this in both the Affinity-1 and Affinity-2 studies and again in the STAT. If they took more to start much of the second dosing may not be needed. The issue is fear of hypoglycemia and poor packaging. The cartridges should never have been called units as current insulin users are equating it to what they are taking with an RAA. MNKD has known for a very long time you need about 1.5x to equate.
Second dosing was actually in the Affinity-1 protocol but was not widely used. There was one doctor out of NC who had his patients proactively checking BG and second dosing and his PWDs blew away the RAA A1c numbers. During the ADCOM one of the FDA evaluation team members actually accused the doctor of cheating. When she told him he would have gotten the same results with his RAA patients if he second dosed them, his response was he would have killed his patients.
If you listen to the John Hopkins dinner www.youtube.com/watch?v=muBuxTqxmQo at about minute 28 Al starts talking diabetes. He mentions with the T1s some slight titration will still be needed but with the T2s you really need to try to get a hypo.
Winston a T2 mentioned last week he was out golfing, taking an 8u when he knew he only needed a 4u prior to a sandwich. Can you imagine taking twice the amount of an RAA than what you knew you should take? Instead of feeling a little light headed they would be calling 911 by the 8th green.
The bottom line is MNKD is one of the most snake bite companies of all time. When they needed their founder the most he got sick and passed. He hoped SNY would do the right thing but months after doing the deal they fire their CEO and bring in Brandicourt. Whether SNY intentionally screwed the pooch or not only Brandicourt knows for sure. In the process too much corporate knowledge was lost.
The great news is Dr. Kendall knows what he is doing and knows his job is to make afrezza the T1 and T2 standard. He says its the easiest job he has ever had. I sure hope he is right and thank God for Amylin as I do not think Mike could have found a better guy to do this and its a near miracle he is at MNKD.
I think the Kendall hire was key here and I like his agressiveness. Stating Afrezza is not only non inferior, but superior to what's out there is pretty huge in my opinion. Really, why in the world would/could it not at least be part of the standard of care if it is in fact non inferior? Add in the fact that it can cause less hypos and it truly is superior - possibly in its own class. |
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Post by mnholdem on Jul 30, 2018 16:56:19 GMT -5
Frankly it just may get its own class. Before agedhippie can chime in, there is plenty of clinical evidence about the effect of faster insulin on first phase insulin release, signaling the liver to shut down glucose production. It's something RAA insulin tries to achieve by dosing pre-meal but doesn't accomplish. If anyone can convince the ADA/AACE that an ultra rapid-acting classification is merited, I think it's David Kendall MD.
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Post by agedhippie on Jul 30, 2018 17:24:33 GMT -5
Frankly it just may get its own class. Before agedhippie can chime in, there is plenty of clinical evidence about the effect of faster insulin on first phase insulin release, signaling the liver to shut down glucose production. It's something RAA insulin tries to achieve by dosing pre-meal but doesn't accomplish. If anyone can convince the ADA/AACE that an ultra rapid-acting classification is merited, I think it's David Kendall MD.
Just to be clear. Dosing pre-meal means at the start of the meal, not 20 minutes beforehand. The Humalog label even says you can dose immediately after the meal and occasionally I do if I don't know what I am going to be eating. There has been some confusion about that in the past. Actually I think if anyone can convince the ADA/AACE that an ultra rapid acting classification is merited it is Novo Nordisk  |
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Post by sayhey24 on Jul 30, 2018 18:19:38 GMT -5
There is already a category in the standard for afrezza. Its called Inhaled Insulin.
Inhaled insulin is available for prandial use with a more limited dosing range. It is contra-indicated in patients with chronic lung disease such as asthma and chronic obstructive pulmonary disease and is not recommended in patients who smoke or who recently stopped smoking. It requires spirometry (FEV1)testing to identify potential lung disease in all patients prior to and after starting therapy.
I guess it could be more negative but wait YES in the T1 section it is -
Rapid-acting inhaled insulin used before meals in patients with type 1 diabetes was shown to be noninferior when compared with aspart insulin for A1C lowering, with less hypoglycemia observed with inhaled insulin therapy (21). However, the mean reduction in A1C was greater with aspart (-0.21% vs. -0.40%,satisfying the noninferiority margin of 0.4%), and more patients in the insulin aspart group achieved A1C goals of #7.0% (53 mmol/mol) and #6.5% (48mmol/mol). Because inhaled insulin cartridges are only available in 4-, 8-, and 12-unit doses, limited dosing increments to fine-tune prandial insulin doses in type 1 diabetes are a potential limitation.
In other words - its Junk! Good Grief who from MNKD allowed this to be afrezza's representation in the Standard? As a doctor if this is all you know about "inhaled Insulin" you would never prescribe it. Its a near miracle they are doing 500 scripts a week.
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Post by mnholdem on Jul 30, 2018 18:19:45 GMT -5
It doesn’t matter to me which horse pulls the “ultra” wagon to the barn.
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Post by cjm18 on Jul 30, 2018 18:20:33 GMT -5
Frankly it just may get its own class. Before agedhippie can chime in, there is plenty of clinical evidence about the effect of faster insulin on first phase insulin release, signaling the liver to shut down glucose production. It's something RAA insulin tries to achieve by dosing pre-meal but doesn't accomplish. If anyone can convince the ADA/AACE that an ultra rapid-acting classification is merited, I think it's David Kendall MD.
Looking forward to earnings call to hear about the label changing “short” trial they are doing. |
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Post by goyocafe on Jul 30, 2018 18:21:46 GMT -5
Frankly it just may get its own class. Before agedhippie can chime in, there is plenty of clinical evidence about the effect of faster insulin on first phase insulin release, signaling the liver to shut down glucose production. It's something RAA insulin tries to achieve by dosing pre-meal but doesn't accomplish. If anyone can convince the ADA/AACE that an ultra rapid-acting classification is merited, I think it's David Kendall MD.
Just to be clear. Dosing pre-meal means at the start of the meal, not 20 minutes beforehand. The Humalog label even says you can dose immediately after the meal and occasionally I do if I don't know what I am going to be eating. There has been some confusion about that in the past. Actually I think if anyone can convince the ADA/AACE that an ultra rapid acting classification is merited it is Novo Nordisk “Actually I think if anyone can convince the ADA/AACE that an ultra rapid acting classification is merited it is Novo Nordick.” Actually, that’s ok by me. Fiasp won’t end up in that new class by itself, and when compared to Afrezza, won’t hold a candle to the timing difference. Now if the ADA will acknowledge 1st pass insulin response as a desired effect in the standard of care, there’s only one insulin, and possibly only one medication that can do that. |
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Post by peppy on Jul 30, 2018 18:27:57 GMT -5
There is already a category in the standard for afrezza. Its called Inhaled Insulin. Inhaled insulin is available for prandial use with a more limited dosing range. It is contra-indicated in patients with chronic lung disease such as asthma and chronic obstructive pulmonary disease and is not recommended in patients who smoke or who recently stopped smoking. It requires spirometry (FEV1)testing to identify potential lung disease in all patients prior to and after starting therapy. I guess it could be more negative but wait YES in the T1 section it is - Rapid-acting inhaled insulin used before meals in patients with type 1 diabetes was shown to be noninferior when compared with aspart insulin for A1C lowering, with less hypoglycemia observed with inhaled insulin therapy (21). However, the mean reduction in A1C was greater with aspart (-0.21% vs. -0.40%,satisfying the noninferiority margin of 0.4%), and more patients in the insulin aspart group achieved A1C goals of #7.0% (53 mmol/mol) and #6.5% (48mmol/mol). Because inhaled insulin cartridges are only available in 4-, 8-, and 12-unit doses, limited dosing increments to fine-tune prandial insulin doses in type 1 diabetes are a potential limitation. In other words - its Junk! Good Grief who from MNKD allowed this to be afrezza's representation in the Standard? As a doctor if this is all you know about "inhaled Insulin" you would never prescribe it. Its a near miracle they are doing 500 scripts a week. my rewrite. I am not an editor. Inhaled insulin is available for prandial use with a more limited dosing range. It is contra-indicated in patients with chronic lung disease such as asthma and chronic obstructive pulmonary disease and is not recommended in patients who smoke or who recently stopped smoking. It requires spirometry (FEV1)testing to identify potential lung disease in all patients prior to and after starting therapy. I guess it could be more negative but wait YES in the T1 section it is - Rapid-acting inhaled insulin used before meals in patients with type 1 diabetes was shown to be noninferior when compared with aspart insulin for A1C lowering, with less hypoglycemia observed with inhaled insulin therapy (21). However, the mean reduction in A1C was greater with aspart *secondary to the increased hypoglycemic rates (-0.21% vs. -0.40%,satisfying the noninferiority margin of 0.4%), and more patients in the insulin aspart group achieved A1C goals of #7.0% (53 mmol/mol) and #6.5% (48mmol/mol) * achieved secondary to increased hypoglycemia. Because inhaled insulin cartridges are only available in 4-, 8-, and 12-unit doses, limited dosing increments to fine-tune prandial insulin doses in type 1 diabetes are a potential limitation. *Afrezza, non-inferior fast acting insulin. 30% less hypoglycemia. Phase one and phase two insulin reaction. Keeps your blood glucose from going high in the first place. |
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Post by rockstarrick on Jul 30, 2018 18:47:19 GMT -5
Frankly it just may get its own class. Before agedhippie can chime in, there is plenty of clinical evidence about the effect of faster insulin on first phase insulin release, signaling the liver to shut down glucose production. It's something RAA insulin tries to achieve by dosing pre-meal but doesn't accomplish. If anyone can convince the ADA/AACE that an ultra rapid-acting classification is merited, I think it's David Kendall MD.
Just to be clear. Dosing pre-meal means at the start of the meal, not 20 minutes beforehand. The Humalog label even says you can dose immediately after the meal and occasionally I do if I don't know what I am going to be eating. There has been some confusion about that in the past. Actually I think if anyone can convince the ADA/AACE that an ultra rapid acting classification is merited it is Novo Nordisk I’m not so sure about that aged,, Things change, and so does the way they are changed. I’ve watched videos of Fiasp @ work via CGM, and it doesn’t even come close to being as fast as Afrezza when coupled with the same CGM. People are seeing this over and over and over !!! It’s different when you can actually watch how the two products work in “real time”. Afrezza is most definitely in a class of its own when it comes to speed and control IMO, and as I said, you, me, and everyone that wants to see it, can watch it in real time now, over, and over, and over. You actually think the FDA, or those setting the Standards are going to just continue playing dumb ?? It is what it is, but unless these CGM’s are feeding us BS, Afrezza is hands down the fastest Mealtime Insulin Product available. The Videos, (not trials), are out there !! It’s kind of like a whole bunch of people seeing Bigfoot,,,, over, and over, and over !! eventually, everybody will quit mocking the messengers and start looking for Bigfoot. It’s definitely getting interesting around here. ✌🏻😎 |
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Post by sayhey24 on Jul 30, 2018 18:52:44 GMT -5
Aged - keep reading and what does the standard say about afrezza? In not so many words its junk when compared to RAAs because RAAs reduce A1c better.
I agree with you as I too think making the needed changes are a huge effort. On the other hand Dr. Kendall thinks its the easiest job he has ever had. Given the scientific board he easily put together I have to give him the benefit of the doubt. At this point the market is not.
As far as the GLP-1s go, they are a disaster. There is some discussion that this class of drugs is so unsafe the entire class will be pulled. There is a suit in the 9th circuit which should be ruled on soon concerning Januvia, Byetta and Victoza over pancreatic cancer and pancreatitis. Here is a good summary on it - www.drugwatch.com/januvia/litigation/As bad as these are Trulicity may be even worse, if thats possible. It was approved on 5 small studies.
It already comes with an FDA ‘black box’ warning about its risks of medullary thyroid cancer and other thyroid tumours. It was approved on the basis of just five small clinical trials (less than is usual for this kind of drug). The FDA has required the Eli Lilly to carry out five ‘post-marketing studies’, including an assessment of cardiovascular risks in people with type 2 diabetes as there is concern it may cause heart attacks too.
And, the FDA approved last August to have the label add additional warnings about the 15 people who died from anaphylactic reactions, anaphylaxis, and angioedema. Thats on top of the other adverse events, including gastroenteritis Escherichia coli, adenocarcinoma pancreas, pancreatic carcinoma metastatic, diabetic ketoacidosis, and pancreatic carcinoma.
Januvia is a DPP-4, the others are GLP-1 though. Why are they mixing up the classes? There is zero chance of GLP-1 being pulled from the market. On the contrary you are going to see the ADA/EASD Consensus Statement in October push it to the front of Type 2 treatment directly behind or alongside metformin. If you have CVD then SGLT-2 will preempt it. That aside the LEADER trial killed the CV risk stone dead with this in the conclusion of the study - In the time-to-event analysis, the rate of the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke among patients with type 2 diabetes mellitus was lower with liraglutide than with placebo. The lawsuit dies because the LEADER trial found no evidence to support the claims. LEADER was a 9,830 person long term trial (Category A evidence) to look at all cause mortality, and CVD in users of GLP-1. The findings were that there are no CVD risks, and there is no provable cancer risk, that is it's not proven, and it's not cleared - courtesy of the FDA Oncology group evaluation of the LEADER results. All drugs carry risk, the question is whether the benefit outweighs the risk. In the first instance that is the FDA's call, and subsequently the doctor's call. There is no sign the FDA or doctors are going to change their position of GLP-1, and LEADER cements that. Remember Afrezza still has to conduct " A 5-year, randomized, controlled trial in 8,000-10,000 patients with type
2 diabetes to assess the serious potential risk of pulmonary malignancy with
Afrezza use" and has a lung cancer risk right there on the label. I doubt anyone here expects that to go badly, same applies to most drugs.
Aged - I don't know why they consolidate the DDP4 and GLP1s. I think its because its all about labeling. The lawsuit is not about the drugs killing people. The BPs already admitted to that. They just did not put it on the labels. The reality is both classes once Dr. Kendall does his job should be pulled from the market.
Lilly and the FDA both thought the other GLP1s might get pulled and why they agreed to the 5 small studies to rush it to market.
The Big Dog behind the GLP-1s push is Ralph DeFronzo, the same guy who brought us metformin and who now says its the biggest waste in T2 treatment. He thinks combining GLP-1 with Actos is a great idea and short term results in the Qatar study are good and show beta cell regeneration. At the same time Ralph is talking about the SGLT-2 amputation risks. If you want to stop CVD - stop the spike and nothing does it better than afrezza. Doing it with GLP1s and TZDs are down right dangerous. If you stop the spike with afrezza you don't need the SGLT-2s to piss out the sugar.
The bottom line is if Dr. Kendall does his job which he says is the easiest job he has every had, SGLT-2s, DDP4s and GLP1s are obsoleted. But then again Lantus sales will also take a huge hit. Its just a matter of time and the question of MNKD having enough money to hang in there.
The afrezza potential risk of pulmonary malignancy with Afrezza and the warning on the label which says it has a lung cancer risk are left overs from Exubera. Pfizer did their best to poison the well. Lets see what Dr. Kendall can do to rectify this with the lost studies. The first puff was taken in 1998 and what is clear after being approved 4 years ago, no one is seeing lung issues with long time afrezza use and they won't. FDKP does not accumulate and is inert. I know "cancer" is the last thing to throw at afrezza but tree pollen is a bigger issue as is going outside in NYC smog.
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Post by agedhippie on Jul 30, 2018 19:39:46 GMT -5
I should have been clearer. I think if anyone can get the ultra rapid class it is Novo Nordisk because they know how the game is played and have the political capital to get it done. Dr Kendall also knows how the game is played, but lacks the organizational political capital to get it done outright. It is going to be far easier to let Novo Nordisk do the heavy lifting and step in at the end with a me too application.
The hard thing is getting a new class, the easier thing is getting into the class.
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Post by akemp3000 on Jul 30, 2018 19:49:21 GMT -5
Dr. Kendall will base his recommendation on facts showing ultra-rapid in AND OUT (comparatively speaking) which Novo cannot do. Novo certainly has had more influence in the past but Dr. Kendall has the better cards to play moving forward.
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Post by sayhey24 on Jul 30, 2018 19:59:21 GMT -5
Aged - I thought the current rapid acting class was "rapid acting insulin analog". Thats what is on the labels. Afrezza is currently in the Inhaled Insulin category. Its called rapid acting inhaled insulin on the label.
What do you think this new class that Novo Nordisk is going to get is - ultra rapid acting insulin analog? Afrezza is not an analog and FIASP is not "ultra". It doesn't peek fast enough and it hangs around way too long.
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Post by morgieporgie on Jul 30, 2018 20:06:48 GMT -5
Dr. Kendall will base his recommendation on facts showing ultra-rapid in AND OUT (comparatively speaking) which Novo cannot do. Novo certainly has had more influence in the past but Dr. Kendall has the better cards to play moving forward. Would be great if it was that easy! Should be, right? In a perfect world I guess that would do the trick. Unfortunately, many people's pockets will need to be stuffed with cash for that to happen. Also, I do think the endocrinologists won't really push Afrezza cuz it probably puts more control into the Afrezza user than the endo. Certainly makes less office visits, no? |
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