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Post by peppy on Jul 29, 2017 16:42:19 GMT -5
While MNKD may have constraints on using this in their sales activities (I don't know), patients certainly would be free to present this to their docs. Hopefully some will start doing that. Some docs simply aren't open to receiving info from patients but others are. Of those that are actually willing to read it, it would be very interesting as to whether it ends up being persuasive. Hard to assess the impact of this without getting some feedback about how real world practicing physicians view it. I still think a chart or graph showing how A1c drops over period of months for the cohort would have been powerful (especially with the note "no serious hypos"). Perhaps breaking into subgroups as well... those previously using prandial subq and uncontrolled vs new to prandial, those with and without CGM. Maybe they still don't have enough patient months of data to make that look conclusive. Hopefully it is coming. dream, the cruise, what an awful storm we have been in. The think the weather is clearing. scripts. mannkind only needs @ 40,000 users to break even? all aboard.
Onset of activity for TI occurred ca. 25-35 minutes earlier than for Lispro. TI duration of action is about 2 hours shorter than an equivalent dose of Lispro. Dose-response was almost linear up to 48U TI and 30 U Lispro.
• To elicit the same GIRmax, ~40% more Afrezza is required (e.g., a 4 unit cartridge of Afrezza and 2.8 U Lispro produce the same GIRmax The PD response of 4 U Afrezza and 1.6 U Lispro are equivalent (e.g., 20 units Afrezza produces the same GIR AUC.
Each 4 unit Afrezza cartridge provides approximately the same insulin exposure as 3.1 U Lispro
www.mannkindcorp.com/Collateral/Documents/English-US/Baughman%20poster%20100-LB%20FINAL%20X2.pdf
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Post by sportsrancho on Jul 29, 2017 16:49:32 GMT -5
Rock - did you also send this to every Big Pharma President? I have been saying for a while afrezza has been living in their heads "Rent Free" since ADA 2017. It would also be nice to send it to every money manager in the diabetes space AFTER everyone here finalizes their positions on Monday. What Mike now needs to deal with is direct to consumer distribution and pricing which I suspect he has a plan for. I been sharing it randomly all over the place, unfortunately, duty calls, I have an Outdoor Concert on the Washington Coast, right on the Ocean. I guess there's Bands playing all day, (we are the headliner), so I think I'll leave early and make a day of it. Have a Great Day Everyone 🎸🇺🇸
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Post by dreamboatcruise on Jul 29, 2017 16:58:17 GMT -5
While MNKD may have constraints on using this in their sales activities (I don't know), patients certainly would be free to present this to their docs. Hopefully some will start doing that. Some docs simply aren't open to receiving info from patients but others are. Of those that are actually willing to read it, it would be very interesting as to whether it ends up being persuasive. Hard to assess the impact of this without getting some feedback about how real world practicing physicians view it. I still think a chart or graph showing how A1c drops over period of months for the cohort would have been powerful (especially with the note "no serious hypos"). Perhaps breaking into subgroups as well... those previously using prandial subq and uncontrolled vs new to prandial, those with and without CGM. Maybe they still don't have enough patient months of data to make that look conclusive. Hopefully it is coming. dream, the cruise, what an awful storm we have been in. The think the weather is clearing. scripts. mannkind only needs @ 40,000 users to break even? all aboard.
Onset of activity for TI occurred ca. 25-35 minutes earlier than for Lispro. TI duration of action is about 2 hours shorter than an equivalent dose of Lispro. Dose-response was almost linear up to 48U TI and 30 U Lispro.
• To elicit the same GIRmax, ~40% more Afrezza is required (e.g., a 4 unit cartridge of Afrezza and 2.8 U Lispro produce the same GIRmax
www.mannkindcorp.com/Collateral/Documents/English-US/Baughman%20poster%20100-LB%20FINAL%20X2.pdf
Yeah, the dreamboatcruise ended up being the fateful trip that started as a three hour tour. They're doing an impressive job of strapping together radios from coconuts. Will a rescue ship arrive in time?
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Post by peppy on Jul 29, 2017 17:06:17 GMT -5
dream, the cruise, what an awful storm we have been in. The think the weather is clearing. scripts. mannkind only needs @ 40,000 users to break even? all aboard.
Onset of activity for TI occurred ca. 25-35 minutes earlier than for Lispro. TI duration of action is about 2 hours shorter than an equivalent dose of Lispro. Dose-response was almost linear up to 48U TI and 30 U Lispro.
• To elicit the same GIRmax, ~40% more Afrezza is required (e.g., a 4 unit cartridge of Afrezza and 2.8 U Lispro produce the same GIRmax
www.mannkindcorp.com/Collateral/Documents/English-US/Baughman%20poster%20100-LB%20FINAL%20X2.pdf
Yeah, the dreamboatcruise ended up being the fateful trip that started as a three hour tour. They're doing an impressive job of strapping together radios from coconuts. Will a rescue ship arrive in time? yeah this conference call is going to be interesting. I'll start the count down. 10. our Deerfield drop dead date and all the hiring. Are they going to say a word about what the heck with Matt P? It has been a fateful trip. here on Gilligans isle. Amazing we have all this buried treasure.
How many people using afrezza, do we need to break even?
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Post by thall on Jul 29, 2017 17:06:31 GMT -5
VDEX doesn't appear to be listed on the physician locator on afrezza's website. Why?
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Post by oldfishtowner on Jul 29, 2017 17:14:38 GMT -5
At the risk of being the subject of the ire of other longs on this board, I beg to offer a different opinion of the Vdex paper than the praises being heaped upon it by virtually everyone so far. The paper's observations may well be valid, but the data presented do not support the claims made. Rather in some instances the data seem to contradict the claims. Nor are any references provided to support claims made that are not based on the "study" data. The language and writing style of the paper are not professional. For example, "Who really knows what all this stuff does or how it interacts?"
The paper's author is not given, let alone one with an MD that would lend some credence to its contents. Vdex would have been better off with just a one or two page summary of their findings. As it is, the paper comes off as very amateurish. I would be embarrassed to forward this to anyone, and would certainly not send it to anyone making critical decisions that would affect Afrezza's future.
Granted that there is a disclaimer at the beginning that the paper lacks "some of the rigors" of peer-reviewed articles. Still, I would hazard to say that the paper would deserve an F in any subject, whether it be English class, a technical writing class, or any hard science class.
"Some of our studies were purely observational. We prescribed the drug and monitored the results that patients achieved. From those initial observations, we designed tests to further understand various aspects of the product. We DO NOT attempt here to fully explain how this drug works. It is for others to detail the precise mechanism of action. We sought to understand WHAT the drug does, not necessarily HOW it does it. We will hypothesize about the HOW to the extent we feel comfortable, but we encourage further study by others to completely explain our observations." Some of our studies were purely observational. We prescribed the drug and monitored the results that patients achieved. From those initial observations, we designed tests to further understand various aspects of the product. We DO NOT attempt here to fully explain how this drug works. It is for others to detail the precise mechanism of action. We sought to understand WHAT the drug does, not necessarily HOW it does it. We will hypothesize about the HOW to the extent we feel comfortable, but we encourage further study by others to completely explain our observations." Vdex should have stuck to this approach instead of attempting to explain what is going on in more detail and making general claims not supported by their observations.
In the summary of safety findings the paper states: "Hypoglycemia. Our experience has been that Afrezza is extremely safe for all patients. It appears difficult to induce hypoglycemia even if you try."
This is a dangerous claim. The first statement must be conditioned. You cannot disregard other medications that patients may be taking, especially when you are pretending to give advice to other practitioners. We know that taking Afrezza with metformin or basal insulin can induce hypoglycemia. Although Vdex claims that hypo's cannot be induced in patients with insulin sensitivity, I recall at least one PWD with insulin sensitivity saying the a 4-unit dose resulted in significant hypos, and wished there was a 2-unit dose available. Regarding the second statement, the paper also says, "In fact, we saw less hypoglycemia overall as patients’ blood glucose levels flattened and stabilized." So, patients did experience hypoglycemia. How many and how often? There were only 30 patients, so it cannot be that difficult to induce hypoglycemia if it occurs in the normal course of treatment. What is important, it seems to me, is how Vdex limited the hypoglycemia and flattened the BG levels.
As for the data: Figures 1, 2 & 3. Where did these come from? Particularly Fig 3, BG levels on Afrezza. This chart has 7 curves plotted, one for each day of the week. Is this for one of Vdex's patients for one week? What is it supposed to show or prove? How many of Vdex's patients were able to achieve this? Was this repeatable and for how many weeks has this been achieved? The paper never provides enough information to interpret the significance of this chart.
Fig 3 was certainly not the patient in study#2. "We began treatment and steadily increased dosages of Afrezza until the patient was administering 96 units of insulin each meal or almost 300 units of insulin daily. We DID NOT adjust the basal dosing." According to the clinical studies, 96 units, if taken as a single dose, is well past the point of diminishing returns for Afrezza and fasting BG levels were only reduced to 130-180. Vdex doesn't say if the 96 units were taken at one time or stacked or whatever. Vdex's conclusion, "even massive doses of Afrezza in some patients seem not to produce hypoglycemia." Is this even a meaningful statement regarding a patient with such high BG levels? My conclusion: VDEX couldn't get her BG levels under control. Not a good case study for Afrezza IMO.
In case study 6, Vdex does not explain why the 8-unit dose is apparently less effective than the 4-unit dose. Clearly in 6b (4-unit) the BG is already in range before the second dose is taken. In 6c, with the 8-unit dose BG is higher and stays out of range longer than with the 4-unit dose in 6b. Seems to be counterintuitive. Maybe at this point the patient couldn't cope with yet another 6" turkey sub.
"Given our extensive, direct experience with Afrezza, we have confirmed the safety of the product. " How many patients has Vdex treated with Afrezza? The paper only mentions 30. No one will accept this as extensive experience, especially in the case of a safety study. They may have treated many more, but they never say. They also never say what percentage of their patients reach goal or what the dropout rate is. Isn't this what practitioner's want to know, especially if they are being told that Vdex has found the holy grail of diabetes and to follow their example.
The paper may have a useful message, but it is poorly explained and could, in reality, be counterproductive.
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Post by dreamboatcruise on Jul 29, 2017 17:27:26 GMT -5
oldfishtowner... you raise some fair points. I'm hoping they are collecting more substantial data and will publish it once enough is collected to give some statistical rigor.
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Post by agedhippie on Jul 29, 2017 17:56:09 GMT -5
But could MannKind use this observational study in its marketing? Wouldn't the FDA object? They can't for the reasons cited in the introduction. The introduction says explicitly that it is not up to FDA standards and I suspect they did that to avoid issues with the FDA when it was released. If you are looking for issues the lack of a control set, the population is self-selected, there is a very small population (30 people and a mix of Type 1 and 2), there is a lack of predefined endpoints, and no mention was made of parallel changes (introduction of CGM, or Libre). The paper reads badly as it lacks structure and direction and desperately needs editing. It would be better broken out into a series of shorter papers. As it stands there are a lot of holes in the paper and sections that would be better omitted. I suspect some of this is to do with not having a clear target audience which is problematic if you are trying to use it to persuade people to take you seriously. I found Study #1 interesting and a lot of the others statements of the obvious. The highly insulin resistant patient desperately needs someone to sort out her basal insulin although they seem to have fixed her prandial insulin. It would have been interesting to see if properly titrating her injected prandial insulin would also have fixed the problem. Update: Oldfishtowner beat me to it, and also did a far better job!
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Post by sayhey24 on Jul 29, 2017 17:56:13 GMT -5
Rock - did you also send this to every Big Pharma President? I have been saying for a while afrezza has been living in their heads "Rent Free" since ADA 2017. It would also be nice to send it to every money manager in the diabetes space AFTER everyone here finalizes their positions on Monday. What Mike now needs to deal with is direct to consumer distribution and pricing which I suspect he has a plan for. I thought your position was that all of these people are thinking about Afrezza daily, talking to Mike and following all things MNKD as they are putting final touches on their acquisition offers... yet they need someone from proboards to inform them of a major new study about Afrezza. I guess the rent free space isn't in a very desirable neighborhood of their head... maybe in one of the sinus cavities. Rent Free in their heads. For Brandicourt here is what I will send out to France in a gold foil wrapped box with a nice bow on Monday, the study and a note. The note will say "Idiot, you could have had the greatest advance in diabetes care since 1922 for $25 pps but you got greedy, minimum entry point is now $300 but probably more." I wonder what Marco Rubio thought when he got the case of Trump water? If, what is in this report is true and I have no reason not to believe it is this is industry shattering news. The T2 market is currently close to $40B and headed to $60B. This finally vindicates what many of have been saying since the 171/175 study results where announced. What is in this report mimics what I have personally seen and it parallels what Al Mann said for years. I recently met with a diabetes expert who is a T1 and has just started using afrezza. I told him "go big, always take more than you think you may need and your liver will prevent the low". You should have seen the look he gave me. He clearly thought I was crazy. A week later I get an email "Damn, go big, thats crazy". Now if my theory is correct I bet BG directly correlates to longevity. It sure would be nice to track some 50 yr olds for the next 40 years. Afrezza may not be the fountain of youth but if it can add 10 or 15 years thats not bad but more important whats the value to all the "pre-diabetics". $300 pps is too low Nate Pile is probably closer with his $400 target.
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Post by gamblerjag on Jul 29, 2017 18:00:22 GMT -5
I can see $400 or 40 bilion someday.. Of course that will probably be around 2025.. but do think we see $100/ 10 billion m/c by 2020... and that's not because of a buyout! just based on scripts / techno and future earnings
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Post by straightly on Jul 29, 2017 18:06:22 GMT -5
Wow, wow, wow! We should make large posters of these and give them to doctors when we visit them.
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Post by sayhey24 on Jul 29, 2017 18:19:18 GMT -5
At the risk of being the subject of the ire of other longs on this board, I beg to offer a different opinion of the Vdex paper than the praises being heaped upon it by virtually everyone so far. The paper's observations may well be valid, but the data presented do not support the claims made. Rather in some instances the data seem to contradict the claims. Nor are any references provided to support claims made that are not based on the "study" data. The language and writing style of the paper are not professional. For example, "Who really knows what all this stuff does or how it interacts?" The paper's author is not given, let alone one with an MD that would lend some credence to its contents. Vdex would have been better off with just a one or two page summary of their findings. As it is, the paper comes off as very amateurish. I would be embarrassed to forward this to anyone, and would certainly not send it to anyone making critical decisions that would affect Afrezza's future. Granted that there is a disclaimer at the beginning that the paper lacks "some of the rigors" of peer-reviewed articles. Still, I would hazard to say that the paper would deserve an F in any subject, whether it be English class, a technical writing class, or any hard science class. "Some of our studies were purely observational. We prescribed the drug and monitored the results that patients achieved. From those initial observations, we designed tests to further understand various aspects of the product. We DO NOT attempt here to fully explain how this drug works. It is for others to detail the precise mechanism of action. We sought to understand WHAT the drug does, not necessarily HOW it does it. We will hypothesize about the HOW to the extent we feel comfortable, but we encourage further study by others to completely explain our observations." Some of our studies were purely observational. We prescribed the drug and monitored the results that patients achieved. From those initial observations, we designed tests to further understand various aspects of the product. We DO NOT attempt here to fully explain how this drug works. It is for others to detail the precise mechanism of action. We sought to understand WHAT the drug does, not necessarily HOW it does it. We will hypothesize about the HOW to the extent we feel comfortable, but we encourage further study by others to completely explain our observations." Vdex should have stuck to this approach instead of attempting to explain what is going on in more detail and making general claims not supported by their observations. In the summary of safety findings the paper states: "Hypoglycemia. Our experience has been that Afrezza is extremely safe for all patients. It appears difficult to induce hypoglycemia even if you try." This is a dangerous claim. The first statement must be conditioned. You cannot disregard other medications that patients may be taking, especially when you are pretending to give advice to other practitioners. We know that taking Afrezza with metformin or basal insulin can induce hypoglycemia. Although Vdex claims that hypo's cannot be induced in patients with insulin sensitivity, I recall at least one PWD with insulin sensitivity saying the a 4-unit dose resulted in significant hypos, and wished there was a 2-unit dose available. Regarding the second statement, the paper also says, "In fact, we saw less hypoglycemia overall as patients’ blood glucose levels flattened and stabilized." So, patients did experience hypoglycemia. How many and how often? There were only 30 patients, so it cannot be that difficult to induce hypoglycemia if it occurs in the normal course of treatment. What is important, it seems to me, is how Vdex limited the hypoglycemia and flattened the BG levels. As for the data: Figures 1, 2 & 3. Where did these come from? Particularly Fig 3, BG levels on Afrezza. This chart has 7 curves plotted, one for each day of the week. Is this for one of Vdex's patients for one week? What is it supposed to show or prove? How many of Vdex's patients were able to achieve this? Was this repeatable and for how many weeks has this been achieved? The paper never provides enough information to interpret the significance of this chart. Fig 3 was certainly not the patient in study#2. "We began treatment and steadily increased dosages of Afrezza until the patient was administering 96 units of insulin each meal or almost 300 units of insulin daily. We DID NOT adjust the basal dosing." According to the clinical studies, 96 units, if taken as a single dose, is well past the point of diminishing returns for Afrezza and fasting BG levels were only reduced to 130-180. Vdex doesn't say if the 96 units were taken at one time or stacked or whatever. Vdex's conclusion, "even massive doses of Afrezza in some patients seem not to produce hypoglycemia." Is this even a meaningful statement regarding a patient with such high BG levels? My conclusion: VDEX couldn't get her BG levels under control. Not a good case study for Afrezza IMO. In case study 6, Vdex does not explain why the 8-unit dose is apparently less effective than the 4-unit dose. Clearly in 6b (4-unit) the BG is already in range before the second dose is taken. In 6c, with the 8-unit dose BG is higher and stays out of range longer than with the 4-unit dose in 6b. Seems to be counterintuitive. Maybe at this point the patient couldn't cope with yet another 6" turkey sub. "Given our extensive, direct experience with Afrezza, we have confirmed the safety of the product. " How many patients has Vdex treated with Afrezza? The paper only mentions 30. No one will accept this as extensive experience, especially in the case of a safety study. They may have treated many more, but they never say. They also never say what percentage of their patients reach goal or what the dropout rate is. Isn't this what practitioner's want to know, especially if they are being told that Vdex has found the holy grail of diabetes and to follow their example. The paper may have a useful message, but it is poorly explained and could, in reality, be counterproductive. Maybe you should read the paper again - as the paper says "Figures 1. – 3. below serve to make the point well. The first illustrates typical, non-diabetic glucoselevels as measured on a CGM. The second shows CGM tracings for typical insulin-dependent diabetic blood sugar levels, and the third shows what can be achieved on Afrezza. While not all patients can achieve the level of control reflected in the third graph, ALL AFREZZA USERS THAT WE STUDIED SHOWED FLATTENED CURVES such as we illustrate here. This paper was done for money guys not for doctors and especially not for research types. The 3 figures were presented for illustrative purposes. VDex has no intention of explaining to the money guys how a 2 strand amino acid with a molecular weight of 5808 Da is different and acts different than an analog weighing 5825.8 Da. I suspect Mike has similar results which were done by research scientists which Al left in a file cabinet. Maybe Mike can find them.
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Post by cyn on Jul 29, 2017 18:20:34 GMT -5
This white paper should be forwarded to all 3rd party insurers immediately! They need to read this to better understand why Afrezza should be given Preferred coverage over injected insulin. mnholdem, absolutely agree... sent out ASAP, along with highlighted transcripts from last week's Juvenile Diabetes Congressional hearings referencing unprecedented BG control with Afrezza, especially when used in combination with CGMs. I believe the new 2018 formulary lists get released next month (late August).
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Post by sayhey24 on Jul 29, 2017 18:25:16 GMT -5
I can see $400 or 40 bilion someday.. Of course that will probably be around 2025.. but do think we see $100/ 10 billion m/c by 2020... and that's not because of a buyout! just based on scripts / techno and future earnings Just a few weeks ago some people where saying they would be happy with $2. Its been a good week for Mannkind. Clearly the best in three years. GWPH closed at $117 on Friday. Lets see if we ever hear from RLS again. It took awhile to hear back from VDex.
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Post by derek2 on Jul 29, 2017 18:28:19 GMT -5
Here's what I like (I rolled my eyes at some stuff, but folks on this board could predict what I'd have problems with):
1. The paper is written in plain English and is probably understandable by just about anybody. 2. The author sets out the limitations honestly, instead of conflating wishes and fact. Points for honesty. 3. The narrative is well constructed, taking the reader along the garden path to the conclusion of a different treatment mode.
None of their findings should come as a surprise to anybody on this board, which lends credibility. I'd love to know how many of their patients have tried Afrezza, and the average results that have been achieved, along with retention rates, to give more context to the case studies.
A good effort, IMO, and far less breathless than the content on their website.
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