Something to think about

[bretzyboy]

"Afrezza, on the other hand, has been shown to have remarkable "regenerative" effects on the pancreas and liver". Respectfully I ask - please site sources for the regenerative effects. This alone would have huge potential. Regards.

[mnholdem]

Check out Al Mann's exclusive interview with Amy T. of DiabetesMine, where I believe he actually uses the word "remission":

www.healthline.com/diabetesmine/the-truth-about-afresa-inhalable-insulin-a-chat-with-al-mann#2

Also, you can research "Early Intensive Insulin Treatment" and read any number of studies. If you're able to find one that mentions Afrezza, read that one, because most insulins are not fast enough for effective intensive insulin treatment. Afrezza is perfectly suited for it, and I hope medical scholars are already preparing studies to provide the proof.

[compound26]

I think ML (Granger)'s case also illustrate this regenerative effect of Afrezza.

Here is what she says (under the user name: bob_marylou_granger) on tudiabetes.org: “I have been a Type 1 diabetic for 58 years. After 52 years of thousands of injections, I became needle-phobic. The OUCH you think is minor to you is not minor to millions of others. ….Spent 5 1/2 years in a research study trial using AFREZZA inhaled insulin. I have not had to take an insulin injection during those 5 1/2 years. Believe me, I know that is not a cure. But for now it is the best out there for those of us struggling physically and emotionally with injections.”

www.tudiabetes.org/forum/t/insulin-independence-revolutionary-phase-3-trial-giving-type-1-diabetics-the-promise-of-a-needle-free-life/46721/15

Here is what she says in this forum: 

"When I first joined the MannKind trial, I was injecting Lantus in the morning at breakfast and inhaling Exubera with each meal. Before Exubera had been taken off the market, I had stockpiled quite a large supply. It could be stored on a shelf at room temperature, no refrigeration was needed.

In the beginning, I still took my Lantus at breakfast and then began using the Technosphere {Afrezza as it is now called} with each meal. My BG levels began to drop. My doctor kept lowering the Lantus until he suggested I drop the injections completely. It took me a couple of days to work up my courage, but the idea of not taking ANY shots was worth it. It worked for a few weeks, and then my BG levels started to rise. Terribly disappointed, I went back on the morning Lantus shots and inhaling at each meal. Shortly, my BG levels dropped again, and my doctor took me off injections again. From then on, NO SHOTS!!! No one can explain it --- it just is!

ML
"
mnkd.proboards.com/thread/2135/recent-tudiabetes-diabetics-poll#ixzz3hDZioOee

[stevil]

Jul 28, 2015 7:03:04 GMT -5 mnholdem said:

You guys are talking about domination of the market for Type 1 diabetics, who require daily basal injections (albeit allegedly less units while using Afrezza) and who account for roughly 10% of the diabetes treatment market.

The motherlode that Sanofi is really preparing to dig for is to have Afrezza insulin therapy replace Medformin as the standard first treatment for pre- and early-diabetics. Remember, Medformin doesn't "fix" anything nor keep the pancreas from deteriorating. Afrezza, on the other hand, has been shown to have remarkable "regenerative" effects on the pancreas and liver.

I wouldn't worry about Sanofi executives fretting over the impact on Lantus, when there is a whole world of Type 2 treatment with the potential to generate many times the revenue that Lantus/Toujeo account for.

Some pharmaceutical executives may frown on the idea of "remission" since it means that, unlike Type 1's, many early Type 2 patients may only need to receive intensive therapy for a relatively short period of time using Afrezza. Then, when the pancreas has "rested" and their bodies' control of blood glucose appears to be functioning normally again, they need only maintain a regimen of diet and exercise. 

Stop and think about the PR benefits to a pharmaceutical company for a drug like that. Medformin cannot make that claim, nor any analog insulin, GLP-1's or the latest and greatest within the "alphabet soup" of diabetes treatments.

Afrezza is the only one which will have the ability to boast that it may be effectively used initially as a short-term treatment to stop the deterioration of the pancreas and, in essence, to stop the progression and possibly even remission of this destructive disease at its onset.

Afrezza truly represents a paradigm shift in the treatment of diabetes that can and will add years to the lives of millions, lives that can be lived normally.  It's a fact not being overlooked by Sanofi and it should NOT be overlooked by long-term investors in MNKD.

I worked in the pharmacy in undergrad and unfortunately I don't see Afrezza overtaking metformin anytime soon, if ever, as the drug of choice for physicians. It would take an amazing amount of momentum to change the sentiment of stubborn docs. They get in habits and prescribe what they're comfortable with and what they know. They know metformin works. And, most importantly, it's cheap. It's a $4 drug vs. $400/month. I don't see either physicians or patients choosing the more expensive option unless afrezza can cure type 2s and reverse diabetes. As a maintenence med it doesn't make much sense unless the patient has deep pockets.

Here's to hoping afrezza can cause a paradigm shift.

[bioexec25]

Stevil, docs are stubborn but they're not stupid. They can and will see the difference between a disease resistance therapy like Met versus a disease remission therapy like Afrezza. Maybe this is a subtlety of language but i believe this is already a paradigm shift it's just a matter of how quickly and to what extent it is realized and leveraged to prevent disease progression and save lives.

[joeypotsandpans]

Jul 29, 2015 0:12:57 GMT -5 stevil said:

Jul 28, 2015 7:03:04 GMT -5 mnholdem said:

You guys are talking about domination of the market for Type 1 diabetics, who require daily basal injections (albeit allegedly less units while using Afrezza) and who account for roughly 10% of the diabetes treatment market.

The motherlode that Sanofi is really preparing to dig for is to have Afrezza insulin therapy replace Medformin as the standard first treatment for pre- and early-diabetics. Remember, Medformin doesn't "fix" anything nor keep the pancreas from deteriorating. Afrezza, on the other hand, has been shown to have remarkable "regenerative" effects on the pancreas and liver.

I wouldn't worry about Sanofi executives fretting over the impact on Lantus, when there is a whole world of Type 2 treatment with the potential to generate many times the revenue that Lantus/Toujeo account for.

Some pharmaceutical executives may frown on the idea of "remission" since it means that, unlike Type 1's, many early Type 2 patients may only need to receive intensive therapy for a relatively short period of time using Afrezza. Then, when the pancreas has "rested" and their bodies' control of blood glucose appears to be functioning normally again, they need only maintain a regimen of diet and exercise. 

Stop and think about the PR benefits to a pharmaceutical company for a drug like that. Medformin cannot make that claim, nor any analog insulin, GLP-1's or the latest and greatest within the "alphabet soup" of diabetes treatments.

Afrezza is the only one which will have the ability to boast that it may be effectively used initially as a short-term treatment to stop the deterioration of the pancreas and, in essence, to stop the progression and possibly even remission of this destructive disease at its onset.

Afrezza truly represents a paradigm shift in the treatment of diabetes that can and will add years to the lives of millions, lives that can be lived normally.  It's a fact not being overlooked by Sanofi and it should NOT be overlooked by long-term investors in MNKD.

I worked in the pharmacy in undergrad and unfortunately I don't see Afrezza overtaking metformin anytime soon, if ever, as the drug of choice for physicians. It would take an amazing amount of momentum to change the sentiment of stubborn docs. They get in habits and prescribe what they're comfortable with and what they know. They know metformin works. And, most importantly, it's cheap. It's a $4 drug vs. $400/month. I don't see either physicians or patients choosing the more expensive option unless afrezza can cure type 2s and reverse diabetes. As a maintenence med it doesn't make much sense unless the patient has deep pockets.

Here's to hoping afrezza can cause a paradigm shift.

Excuse me, but I would like to keep my memory intact as much and for as long as possible:

www.kpbs.org/news/2013/apr/12/scripps-researchers-find-culprit-alzheimers-relate/

also,

Metformin, Other Antidiabetic Drugs, and Risk of Alzheimer's Disease

www.medscape.com/viewarticle/764413_1

[mnholdem]

It helps to remember that the early intensive insulin therapy may only be needed for a short period of time. Medformin is widely accepted as just the beginning of a lifetime of treatment, which eventually will include insulin once the pancreas is sufficiently damaged. There are many endocrinologists who would disagree with stevil's remark that Medformin works.

For some reason, the articles Joey posted links to reminded me of the old saying, "It's not nice to fool Mother Nature." There is usually a physiological price to be paid with most drugs. Afrezza does NOT fool the body. It simply provides what the body needs - human insulin and the various signals human insulin sends to the brain and liver. It's why we are seeing very positive results with early adopters.

[stevil]

Jul 29, 2015 16:55:29 GMT -5 mnholdem said:

It helps to remember that the early intensive insulin therapy may only be needed for a short period of time. Medformin is widely accepted as just the beginning of a lifetime of treatment, which eventually will include insulin once the pancreas is sufficiently damaged. There are many endocrinologists who would disagree with stevil's remark that Medformin works.

For some reason, the articles Joey posted links to reminded me of the old saying, "It's not nice to fool Mother Nature." There is usually a physiological price to be paid with most drugs. Afrezza does NOT fool the body. It simply provides what the body needs - human insulin and the various signals human insulin sends to the brain and liver. It's why we are seeing very positive results with early adopters.

I don't know why but it's extremely difficult taking criticism from someone who doesn't have an inkling of knowledge on the subject - you don't even know how to spell the drug. You probably have no healthcare background.

I have worked in healthcare for over 8 years in a few different positions. I have had thousands of hours of patient interaction as it pertains to cost of medication and how that determines the method of care for the patient.

Look, I'm long this stock and I'm holding on to it. I will never state that Afrezza is on the same level or only slightly superior to metformin. I'm saying that there has been a standard of care for years. Metformin first, insulin once the pancreas gets too damaged. That's the way it is and it won't change until Afrezza comes down in cost on copays. Afrezza will mostly appeal to affluent patients who have the luxury of being able to afford the medication. I've seen it thousands of times- patients choose lesser drugs based on cost. Metformin does work. I'm sure you can find endocrinologists that will dispute that. I'd be willing to bet the vast majority would disagree with those select few. Check out metformin script #s and let me know what you find. There have been dozens of diabetes meds that have come out since glucophage, but it's still the standard of care. Docs are familiar with it and there hasn't been anything disruptive enough to replace it. Hopefully Afrezza will. But it only will with either insanely successful research and/or it comes down in price significantly.

My point (opinion) is Afrezza will not be the standard of care for type 2s anytime soon, if at all. Both research and cost will take years. The type 1 market is our best imo for sales. 

I hope Im wrong. I'm not trying to start a pissing match. I'm trying to add my perspective based on experience. Anyone expecting this to sell like hot cakes wasn't stupid, they were just naive. Matt has been saying for a while, "we're not there yet." This will take time. I'm just hoping this can move quickly enough to beat stem cell regeneration. Harvard has already started research on it and it sounds like it's in phase 1 trials. That's the only thing that can beat Afrezza.

hsci.harvard.edu/news/stem-cells-billions-human-insulin-producing-cells

[mnholdem]

Attacking one's incorrect spelling of Metformin (brands Fortamet, Glumetza, Glucophage, Riomet) is a pretty lame technique for winning an argument (chuckle). That said, I would also admit that you would win the argument that my being an executive for 35 years, currently with a international group of over a dozen medical device companies, does not automatically mean I am an encyclopedia of healthcare knowledge.

Eight years of patient interaction is significant and I don't dismiss it in the least - in fact, I truly value your viewpoint. I agree with the words, "anytime soon" in your statement that, "My point (opinion) is Afrezza will not be the standard of care for type 2s anytime soon, if at all. Both research and cost will take years," but I disagree with your use of "if at all", as well as your statement that "The type 1 market is our best imo for sales." I also acknowledge your "imo" indicates that you are penning your opinion, as I was mine. I am not arguing as much as explaining that Sanofi plans to target the Type 2 diabetic market with Afrezza, a fact which they presented at conference in Paris earlier this year. The CEO at the time called it, "the lost decade" to describe the millions of insulin-adverse patients prescribed to Metformin.

If I were to point out a weakness (if not a contradiction) in your opinion, it would be that you acknowledge "Metformin first, insulin once the pancreas gets too damaged." By making that statement, you seem to be implying that, even if Afrezza is proven to lead to remission of diabetes in many (though not all) diabetics, a paradigm shift in a decades-old standard of care by the medical community will remain standing, due primarily to the cost of the new treatment. Paying $300-$400(?) per month for a possible, though yet to be empirically proven, treatment that may result in remission of the disease versus $4 for a drug that only delays the disease, I would think to be a no-brainer.

I am not saying that changing a standard won't be difficult. Insurers often appear to favor the lowest short-term cost over long-term health savings and pharmaceutical giants may also prefer sticking a patient (pardon the pun) with a life-long treatment (or should I say revenue stream) over a treatment that may only be necessary for a short period of time.

Incidentally, I do have more than an inkling of knowledge, having perused dozens of medical journals on the subject of early intensive insulin therapy, some dating back 25 years. Until now, no commercially available drug had the PK/PD profile that is needed for this widely-published therapy, a treatment which numerous studies (which administered insulin intravenously) have confirmed can repair the pancreas if applied at an earlier stage of pancreatic dysfunction. Medical academia has been arguing the merits of early intensive insulin therapy as the best "first choice treatment" topic for decades.

With Afrezza inhalable human insulin, academia now has a monomeric insulin that may be used to provide the empirical evidence necessary for the changing of a decades-old standard of care for diabetes treatment. It's my belief that multiple studies will be conducted during the ensuing decade that will validate what Alfed Mann and other scientists have been advocating for years.

Money is important, I'll grant you that. But the potential for Afrezza therapy to stop the disease at its onset changes the landscape. Frankly, I know without a doubt that my physician (who has been my primary care physician for 40 years) would prescribe the best treatment for me, not the cheapest. Other physicians and healthcare professionals may not.

Perhaps nowadays, drug cost has become the primary criteria for determining the "standard of care" for best treatment option, within our medical community. I certainly hope not.

Some day another treatment (such as the stem cell research you mention) may become a better choice than Afrezza. Until then, however, there is simply no available treatment that can compare to Afrezza.

[Deleted]

Jul 30, 2015 8:07:07 GMT -5 mnholdem said:

Attacking one's incorrect spelling of Metformin (brands Fortamet, Glumetza, Glucophage, Riomet) is a pretty lame technique for winning an argument (chuckle). That said, I would also admit that you would win the argument that my being an executive for 35 years, currently with a international group of over a dozen medical device companies, does not automatically mean I am an encyclopedia of healthcare knowledge.

Eight years of patient interaction is significant and I don't dismiss it in the least - in fact, I truly value your viewpoint. I agree with the words, "anytime soon" in your statement that, "My point (opinion) is Afrezza will not be the standard of care for type 2s anytime soon, if at all. Both research and cost will take years," but I disagree with your use of "if at all", as well as your statement that "The type 1 market is our best imo for sales." I also acknowledge your "imo" indicates that you are penning your opinion, as I was mine. I am not arguing as much as explaining that Sanofi plans to target the Type 2 diabetic market with Afrezza, a fact which they presented at conference in Paris earlier this year. The CEO at the time called it, "the lost decade" to describe the millions of insulin-adverse patients prescribed to Metformin.

If I were to point out a weakness (if not a contradiction) in your opinion, it would be that you acknowledge "Metformin first, insulin once the pancreas gets too damaged." By making that statement, you seem to be implying that, even if Afrezza is proven to lead to remission of diabetes in many (though not all) diabetics, a paradigm shift in a decades-old standard of care by the medical community will remain standing, due primarily to the cost of the new treatment. Paying $300-$400(?) per month for a possible, though yet to be empirically proven, treatment that may result in remission of the disease versus $4 for a drug that only delays the disease, I would think to be a no-brainer.

Perhaps you're correct. Insurers often appear to favor the lowest short-term cost over long-term health savings and pharmaceutical giants may also prefer sticking a patient (pardon the pun) with a life-long treatment (or should I say revenue stream) over a treatment that may only be necessary for a short period of time.

Incidentally, I do have more than an inkling of knowledge, having perused dozens of medical journals on the subject of early intensive insulin therapy, some dating back 25 years. Until now, no commercially available drug had the PK/PD profile to be used for this widely-published therapy, for which numerous studies (which administered insulin intravenously) have confirmed can repair the pancreas why applied at its earliest stage of dysfunction. Medical academia has been arguing the merits of early intensive insulin therapy as the best "first choice treatment" topic for decades.

With Afrezza inhalable human insulin, academia now has a monomeric insulin that may provide the empirical evidence to advocate a changing of an old standard of care. It's my belief that multiple studies will be conducted during the ensuing decade to validate what Alfed Mann and other scientists have advocated numerous times.

Money is important, I'll grant you that. But the potential for Afrezza therapy to stop the disease at its onset changes the landscape. Frankly, I know without a doubt that my physician (who has been my primary care physician for 40 years) would prescribe the best treatment for me, not the cheapest. Other physicians and healthcare professional may not.

Perhaps nowadays, drug cost has become the primary criteria for determining "standard of care" in the medical community. I certainly hope not.

Some day another treatment (such as the stem cell research you mention) may become a better choice than Afrezza. Until then, however, there is simply no available treatment that can compare to Afrezza.

MN, would appreciate your view as a C level exec.  Is there a point at which Brandicort abruptly pulls the plug?  SNY is a big company and their sales team comes with significant costs (as all good sales teams do).  That said, what preys on my mind and I do not think SNY will walk now (their first option is Jan I believe) there comes a point at which the time and capital can be allocated to more productive endeavors.  I still believe in the long haul, Afrezza is a game changer but because it is revolutionary, it may require more time, effort and capital to grow it than originally anticipated.  

I would also be interested in hearing from you and others why we have not seen a bit more robust growth in NRx week to week.  Seems to me there is a base of physicians who have put patients on Afrezza with spectacular results.  Should this not be helping to drive Rx growth at a faster pace than we currently have?  

Me thinks the greatest impediment to Rx growth is the Prior Authorization since it can take valuable time away from healthcare practitioners and office personnel to battle the insurance companies on this.  Spirometry is an issue but the doc or nurse can simply tell patient Doe to go down the street and get it done.  Spirometry delays the process a bit but does not place the same demands on the doctor or office staff's time.  Hopefully the chatter is true that health plans are starting to drop the prior auth requirement.  

[mnholdem]

This is ENTIRELY speculative, but I am of the opinion that Sanofi has intentionally limited sales to a few select endocrinologists. Typically, a new drug sees restricted or no coverage during the first 6-12 months post launch, so Sanofi is using this time to gather evidence that it can take to the FDA to improve the label. It's possible that data from European clinical trials and/or other studies of Afrezza will also be presented to the FDA.

Why? Simply because any label that can claim "superior" is worth $billions in revenue. It's no longer MannKind management working with the FDA. This is Sanofi-Aventis at work.

Anytime you have a change in leadership, "the plug" can be pulled on an agreement. However, because of Sanofi's declining revenue in the diabetes market, I would normally expect them to be bolstering that division with better drugs, either via their own R&D pipeline or with partnerships and/or acquisitions.

These are the French, mind you, so traditional values cannot be ignored (as former CEO Chris Vehmacher learned the hard way), but the idea of being able to totally dominate the diabetes space because of Toujeo, Lantus, Afrezza and another Technosphere-delivered GLP-1 diabetes drug under development (ref: March 2015 patent) would be irresistible to the French company, I think. I would be astounded if they were considering ending their agreement with MannKind Corporation.

Sanofi operates at their own pace, which may not be to the liking of MannKind shareholders. For 2Q sales, it appears that many Afrezza fans will be disappointed. However, there are indications now that Sanofi sales reps have been given the green light to expand sales targets and start pushing Afrezza more aggressively.

I expect to see some evidentiary developments to be published in scientific journals and a label improvement. The label improvement was also mentioned by Sanofi in the same Paris presentation where they stated that they were targeting 3.1 million out of 5 million Lantus patients to switch to Afrezza for their choice of prandial insulin to be used with Lantus/Toujeo.

Of course, acquisition of Afrezza or even the entire company cannot be ruled out, but I'll simply state that it is a possibility, although I don't think we're in a Quiet Period preceding a filing. I also wouldn't want to see Sanofi limiting sales in order to intentionally lower share price, but I'm out of my element with a giant of this size, so who knows?

No, I think the primary reason for the limited & focused sales of Afrezza has been to gather evidence, to be used for regulatory, academic and marketing reasons. It's frustrating, not knowing how Sanofi operates, but I think we can all agree that Afrezza faces powerful opposition by the other BPs who have an inkling of what harm Afrezza may cause to their market shares and revenues. I recently posted that Sanofi is in a chess match - they are not about to reveal strategy to their opponents.

I was re-reading the ADCOM transcript the other day and found where a physician questioned FDA about the spirometry test, which had been a recommendation with Exubera, but later became a requirement for Afrezza, even though the FDA presenter clearly indicated that it would remain a recommendation. The way they've handled Afrezza makes me wonder if the FDA is also an opponent? I hope not, but all the more reason for Sanofi to be gathering solid evidence and getting it published. The FDA likely operates differently in the dark than they will in the light of public scrutiny of how they handle new proof of Afrezza's benefits to diabetics.

And so the slow-moving chess match continues. Sanofi is probably several moves ahead of everybody.

-----

Incidentally, years ago I landed a contract with a French company. The CEO joked that it was a pleasure to work with a man who at least knows how to properly use eating utensils. Americans switching their fork to the left hand so cut with their knife with the right hand irritates the hell out of some Frenchmen - my CEO was absolutely correct when he instructed me to learn to use a fork left-handed before I flew to France. Goes to show what I mean about tradition.

[notamnkdmillionaire]

Jul 30, 2015 9:33:18 GMT -5 mnholdem said:

This is ENTIRELY speculative, but I am of the opinion that Sanofi has intentionally limited sales to a few select endocrinologists. Typically, a new drug sees restricted or no coverage during the first 6-12 months post launch, so Sanofi is using this time to gather evidence that it can take to the FDA to improve the label. It's possible that data from European clinical trials and/or other studies of Afrezza will also be presented to the FDA.

Why? Simply because any label that can claim "superior" is worth $billions in revenue. It's no longer MannKind management working with the FDA. This is Sanofi-Aventis at work.

Anytime you have a change in leadership, "the plug" can be pulled on an agreement. However, because of Sanofi's declining revenue in the diabetes market, I would normally expect them to be bolstering that division with better drugs, either via their own R&D pipeline or with partnerships and/or acquisitions.

These are the French, mind you, so traditional values cannot be ignored (as former CEO Chris Vehmacher learned the hard way), but the idea of being able to totally dominate the diabetes space because of Afrezza and another Technosphere-delivered GLP-1 diabetes drug under development (ref: March 2015 patent) would be irresistible to the French company, I think. I would be astounded if they were considering ending their agreement with MannKind Corporation.

Sanofi operates at their own pace, which may not be to the liking of MannKind shareholders. For 2Q sales, it appears that many Afrezza fans will be disappointed. However, there are indications now that Sanofi sales reps have been given the green light to expand sales targets and start pushing Afrezza more aggressively.

I expect to see some evidentiary developments to be published in scientific journals and a label improvement. The label improvement was also mentioned by Sanofi in the same Paris presentation where they stated that they were targeting 3.1 million out of 5 million Lantus patients to switch to Afrezza for their choice of prandial insulin to be used with Lantus/Toujeo.

Of course, acquisition of Afrezza or even the entire company cannot be ruled out, but I'll simply state that it is a possibility, although I don't think we're in a Quiet Period preceding a filing. I also wouldn't want to see Sanofi limiting sales in order to intentionally lower share price, but I'm out of my element with a giant of this size, so who knows?

No, I think the primary reason for the limited & focused sales of Afrezza has been to gather evidence, to be used for authoritative, academic and marketing reasons. It's frustrating, not knowing how Sanofi operates, but I think we can all agree that Afrezza faces powerful opposition by the other BPs who have an inkling of what harm Afrezza may cause to their market shares and revenues. I recently posted that Sanofi is in a chess match - they are not about to reveal strategy to their opponents.

I was re-reading the ADCOM transcript the other day and found where a physician questioned FDA about the spirometry test, which had been a recommendation with Exubera, but later became a requirement for Afrezza, even though the FDA presenter clearly indicated that it would remain a recommendation. The way they've handled Afrezza makes me wonder if the FDA is also an opponent? I hope not, but all the more reason for Sanofi to be gathering solid evidence and getting it published. The FDA likely operates differently in the dark than they will in the light of public scrutiny of how they handle new proof of Afrezza's benefits to diabetics.

And so the slow-moving chess match continues. Sanofi is probably several moves ahead of everybody.

-----

Incidentally, years ago I landed a contract with a French company. The CEO joked that it was a pleasure to work with a man who at least knows how to properly use eating utensils. Americans switching their fork to the left hand so cut with their knife with the right hand irritates the hell out of some Frenchmen - my CEO was absolutely correct when he instructed me to learn to use a fork left-handed before I flew to France. Goes to show what I mean about tradition.

two things, 1) I always thought Sanofi would conduct some type of research to help improve the label so what you have written might be spot on.
2) I don't understand your fork story. You wrote the french get irritated with people using the fork in the left hand but the next sentence you said your CEO told you to learn how to eat with fork in your left hand. Was that to purposely irritate the french? And what if you are actually left handed like me and have always used his left hand to eat with a fork?

[Deleted]

Jul 30, 2015 9:33:18 GMT -5 mnholdem said:

This is ENTIRELY speculative, but I am of the opinion that Sanofi has intentionally limited sales to a few select endocrinologists. Typically, a new drug sees restricted or no coverage during the first 6-12 months post launch, so Sanofi is using this time to gather evidence that it can take to the FDA to improve the label. It's possible that data from European clinical trials and/or other studies of Afrezza will also be presented to the FDA.

Why? Simply because any label that can claim "superior" is worth $billions in revenue. It's no longer MannKind management working with the FDA. This is Sanofi-Aventis at work.

Anytime you have a change in leadership, "the plug" can be pulled on an agreement. However, because of Sanofi's declining revenue in the diabetes market, I would normally expect them to be bolstering that division with better drugs, either via their own R&D pipeline or with partnerships and/or acquisitions.

These are the French, mind you, so traditional values cannot be ignored (as former CEO Chris Vehmacher learned the hard way), but the idea of being able to totally dominate the diabetes space because of Toujeo, Lantus, Afrezza and another Technosphere-delivered GLP-1 diabetes drug under development (ref: March 2015 patent) would be irresistible to the French company, I think. I would be astounded if they were considering ending their agreement with MannKind Corporation.

Sanofi operates at their own pace, which may not be to the liking of MannKind shareholders. For 2Q sales, it appears that many Afrezza fans will be disappointed. However, there are indications now that Sanofi sales reps have been given the green light to expand sales targets and start pushing Afrezza more aggressively.

I expect to see some evidentiary developments to be published in scientific journals and a label improvement. The label improvement was also mentioned by Sanofi in the same Paris presentation where they stated that they were targeting 3.1 million out of 5 million Lantus patients to switch to Afrezza for their choice of prandial insulin to be used with Lantus/Toujeo.

Of course, acquisition of Afrezza or even the entire company cannot be ruled out, but I'll simply state that it is a possibility, although I don't think we're in a Quiet Period preceding a filing. I also wouldn't want to see Sanofi limiting sales in order to intentionally lower share price, but I'm out of my element with a giant of this size, so who knows?

No, I think the primary reason for the limited & focused sales of Afrezza has been to gather evidence, to be used for regulatory, academic and marketing reasons. It's frustrating, not knowing how Sanofi operates, but I think we can all agree that Afrezza faces powerful opposition by the other BPs who have an inkling of what harm Afrezza may cause to their market shares and revenues. I recently posted that Sanofi is in a chess match - they are not about to reveal strategy to their opponents.

I was re-reading the ADCOM transcript the other day and found where a physician questioned FDA about the spirometry test, which had been a recommendation with Exubera, but later became a requirement for Afrezza, even though the FDA presenter clearly indicated that it would remain a recommendation. The way they've handled Afrezza makes me wonder if the FDA is also an opponent? I hope not, but all the more reason for Sanofi to be gathering solid evidence and getting it published. The FDA likely operates differently in the dark than they will in the light of public scrutiny of how they handle new proof of Afrezza's benefits to diabetics.

And so the slow-moving chess match continues. Sanofi is probably several moves ahead of everybody.

-----

Incidentally, years ago I landed a contract with a French company. The CEO joked that it was a pleasure to work with a man who at least knows how to properly use eating utensils. Americans switching their fork to the left hand so cut with their knife with the right hand irritates the hell out of some Frenchmen - my CEO was absolutely correct when he instructed me to learn to use a fork left-handed before I flew to France. Goes to show what I mean about tradition.

Thank you for your comments.  I was under the impression that Sanofi is actively pursuing a label change to claim Afrezza is ultra rapid acting and reduces hypoglycemia and wanted to have the claims approved no later than Q2 16 but perhaps my memory serves me wrong.  

Afrezzauser's endo, Dr. Bode I believe has one of the largest endo practices in the country so to your point maybe he is one of the initial focal points for Afrezza.  IMS has a service called Xponent that tracks specific physician Rx data so Sanofi would have details on how Afrezza is impacting prandial insulin sales & share with key docs.  

Seems like continuous concerns among healthcare practitioners and patients that there have been few truly breakthrough products for people with diabetes.  If Afrezza doesn't fit that bill, I don't know what does.  One would think by now, docs would be reading a bit about Afrezza and raise an eyebrow to the big reductions in A1C and incidences of hypoglycemia.  

My guess is minimal uptick in NRx for the rest of July and most of August.  With the chatter that slowly, the prior authorization issue is declining, I have to believe in September, we should start to see week over week NRx growth at a greater pace than what we have experienced so far.  

[dreamboatcruise]

@scotta:

If recollection serves... somehwere in discussions MNKD has said that mandatory FDA trials will start before those to improve label. We don't yet know of any registered trials that have end points addressing A1c, fasting BG, lower mealtime spike, less hypoglycemia, etc. The speed is already shown in the prescribing info via a graph. PK/PD really isn't disputed, just not deemed worthy of altering the "rapid acting" descriptor.

mnholdem:

Are you expecting that label improvement could be based on published results that were not in an FDA registered trial?  I'll admit I'm not well versed in whether that does/can happen.

[Deleted]

Jul 30, 2015 10:51:50 GMT -5 dreamboatcruise said:

@scotta:

If recollection serves... somehwere in discussions MNKD has said that mandatory FDA trials will start before those to improve label. We don't yet know of any registered trials that have end points addressing A1c, fasting BG, lower mealtime spike, less hypoglycemia, etc. The speed is already shown in the prescribing info via a graph. PK/PD really isn't disputed, just not deemed worthy of altering the "rapid acting" descriptor.

mnholdem:

Are you expecting that label improvement could be based on published results that were not in an FDA registered trial?  I'll admit I'm not well versed in whether that does/can happen.

Good question but I am not sure.  Could trials outside the US for this purpose be accepted by FDA?