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Diabetes and Obesity

Unkind to Mannkind

Last time I mentioned Mannkind and their inhaled-insulin product (Afrezza) around here was when Oliver Brandicourt was announced as taking over at Sanofi. But I’ve had unkind things to say about them over the years, and their retail-investor cult is one of the most bizarre I’ve ever seen.
So now that Afrezza is launched, and Sanofi-fied, how’s it doing? Not so great. Here’s a look from Buyer’s Strike (admittedly not disinterested observers of this sort of thing), but it’s hard to put a good face on things. This reminds me of what Pfizer went through with their own inhaled insulin, Exubera, back in 2007. When that one hit the market, and it was like watching an Olympic dive into a dried-out swimming pool. No one wanted it. And so far, it doesn’t look like many people want Afrezza, either, which is what I (and others) have always wondered about. Is there any reason why people are going to start buying it?

50 comments on “Unkind to Mannkind”

  1. johnnyboy says:

    Cue the Mannkind maniacs: “But Affreza is soooooo different from Exubera, it’s absurd to even compare the two ! And diabetics hate needles sooooo much, this is a sure win !!!”

  2. Anonymous says:

    Great timing, stock is up 11%. Oh and cue the idiots who think it’s the same as exubera. Oh wait they are already here

  3. Matt DeMonte says:

    On-body automtic insulin pumps have run away with the market. Better than repeated shots and avoids the potential problems of insulin inhalers.
    New devices can even measure blood glucose levels through the skin using tiny Raman spectroscopy!
    I wish I would have shorted them a long time ago.

  4. Matt DeMonte says:

    On-body automtic insulin pumps have run away with the market. Better than repeated shots and avoids the potential problems of insulin inhalers.
    New devices can even measure blood glucose levels through the skin using tiny Raman spectroscopy!
    I wish I would have shorted them a long time ago.

  5. alig says:

    Down 40% since Feb even with today’s 10% gain, down 60% over one year, but almost double its price two years ago, so it all depends on when you bought if you see this stock as a winner or loser.

  6. MarkySparky says:

    @2
    Yes, up 11% today. Woohoo!
    Meanwhile:
    YTD: MNKD -23% (S&P +3%)
    1-year: MNKD -42% (S&P +13%)
    5-year: MNKD -31% (S&P +86%)
    I have a bridge for sale…

  7. Hap says:

    Is there a better target for the inhaled drug technology? It seems like this is a case where validating the tech in a known indication costs far more than it’s worth, but maybe something else might work, as opposed to the Exubera inhaler, which would have been great for the medical marijuana market, but not much else.

  8. biotechtoreador says:

    Impressively, investors have poured $2.4 billion into MNKD to develop Affrezza. Makes sense, I guess. Even 5% of the $35 billion annual insulin market over 10 years has an nPV of $5 billion….
    Oddly, despite a 35% cost to borrow shares it’s hard to short MNKD….

  9. Hap says:

    And apparently the people who might want to buy Afrezza think it’s just like Exubera, or at least that how it’s getting bought. Maybe it will get better sales later, but it’s not looking good now.

  10. Anonymous says:

    @5: And if you bought the stock at its low point and sold at its high point every day over the past year, you’re up 10,000%! 🙂

  11. Anonymous says:

    I don’t know much about diabetes treatment, so can someone explain why inhaled versions of insulin such Afrezza and Exubera have not been successful. Do they just not work well?

  12. Anonymous says:

    Probably because of 1) comfort/trust with the habit of injecting; and 2) because the effect of injecting insulin is more immediate than inhaling insulin?

  13. p says:

    I’m a type 1 diabetic (for over 30 years – I was there when it was bovine/porcine insulin and one estimated blood glucose by testing urine). I have no idea how well inhaled insulin would work. I also have very little motivation to try. Delivering insulin has NEVER been the rough part of type 1 diabetes. It’s the part everyone thinks is bad but it really isn’t. An insulin injection is easy to give and essentially painless if done correctly. Response is predictable and quick.
    The two main problems have always been BG testing and making diet and insulin dose work. The latter was addressed for a long time with periodic doses of long acting insulin with boluses of fast acting insulin injected prior to meals. That went away, with much improvement over BG control, with the advent of the insulin pump which can supply a steady dose of insulin with boluses for meals. The steady dose can be adjusted higher at periods of inactivity or increased need (i.e. early morning before awakening) or decreased during periods of high activity. The pump is freaking awesome and a miracle of modern science.
    Also a miracle of modern science, the ability to routinely directly test one’s blood glucose allows much tighter control. If one gets carried away, one can pretty much have normal BG now. The recent advent of constant BG monitoring has taken even that miracle to a new level.
    Not to be lost is the (now quite old) new technology of human insulin obtained via recombinant DNA tech. Insulin resistance is a thing of the past and doses are 1/2-1/3 what they were with bovine/porcine insulin.
    Inhaled technology solves zero problems a type 1 diabetic has. It prevents one from having to inject the insulin, which was never a big deal. Moreover, fewer and fewer type 1 diabetics inject anything now that pumps are abundant and reliable.
    It’s a data point of one, but I have not thought, “Man, if only I didn’t have to inject myself” since approximatly my second month of being diabetic. I have frequently worried about getting too low of BG (before BG monitors) or not being able to control BG during periods of fasting or inactivity (pre-pump) and I’m always worried/irritated about having to think of BG, insulin and carb intake at all but it will require a cure to fix that.
    Basically, inhaled insulin is some clever non-diabetic’s solution to a non-existent problem. It IS clever. And taking injections 5 or 6 times a day would seem like a terrible burden. And, I guess, it is a little. But it isn’t as much of a burden as other areas of diabetes and, in the end, relative to other diseases, isn’t really a burden at all.

  14. Durant says:

    vous êtes un idiot monsieur

  15. blog errors says:

    If I use firefox, this website keeps sending me to ‘gogardenclub.com’. If I use Internet Exploder, I still get this error after months and months:
    Fatal error: Call to undefined function: str_split() in /home/corante/public_html/pipeline/connect.php(1) : regexp code(1) : eval()’d code(1) : regexp code on line 1
    Great blog, can I contribute to a fund to get it moved to a new site?

  16. p says:

    Durant, why is that?

  17. Nick says:

    GS added shares and options to their long position as of today’s reporting. They are playing retails per usual. MNKD is an investment you must decide on for yourself. The author will come to realize that the short thesis is saying diabetics don’t want a simplified method allowing unprecedented BG control. A new paradigm takes time to become established if it overcomes irrational and often times damaging opposition. I have seen doctors from Eli Lilly, Pfizer etc. bash the company and the drug. If no one wants it, why would they care. Same for the GS JPM etc.

  18. Nick says:

    GS added shares and options to their long position as of today’s reporting. They are playing retails per usual. MNKD is an investment you must decide on for yourself. The author will come to realize that the short thesis is saying diabetics don’t want a simplified method allowing unprecedented BG control. A new paradigm takes time to become established if it overcomes irrational and often times damaging opposition. I have seen doctors from Eli Lilly, Pfizer etc. bash the company and the drug. If no one wants it, why would they care. Same for the GS JPM etc.

  19. Some idiot says:

    @13: Thanks for the description… Makes a difference for me hearing what _is_ a problem and what is _not_ a problem… And not from a sales/marketing dude, but someone who deals with it personally every day… Helps me focus on the main reason I am still in this business… To help people (or to try to, at any rate…). And we do that by listening and then thinking, not the other way around (or, worse, thinking and then telling…).

  20. Chrispy says:

    #13p:
    Thanks for commenting — it is really informative to hear it from a patient’s perspective.

  21. Kazoo Chemist says:

    @13 – Your post is a great analysis of the issue from the patient perspective. Your sentence: “Basically, inhaled insulin is some clever non-diabetic’s solution to a non-existent problem” says it all. Thanks for your perspective.
    @15. I have also learned a lot about gardening today. This problem is new for me. I finally cleared all of my Safari history on my iPad and it seems to have helped. Tomorrow I might learn about when it will be best to get the beans planted.

  22. Kazoo Chemist says:

    @13 – Your post is a great analysis of the issue from the patient perspective. Your sentence: “Basically, inhaled insulin is some clever non-diabetic’s solution to a non-existent problem” says it all. Thanks for your perspective.
    @15. I have also learned a lot about gardening today. This problem is new for me. I finally cleared all of my Safari history on my iPad and it seems to have helped. Tomorrow I might learn about when it will be best to get the beans planted.

  23. Anonymous says:

    @13: Thanks, that is one of the best and most informative comments I have read here in a long time. It reminds me that scientists often (but certainly not always) invent solutions without speaking to patients to understand the problem, or even to check if there really is a problem. Then they end up with solutions looking for problems, thus creating problems that never existed in the first place.

  24. Kazoo Chemist says:

    Speaking of problems with corante. I just got the frequent Double Post “feature”. You press the post button and it seems that nothing happens. You press it again and you get the same result. The screen is stuck in limbo land with the progress bar at the top just standing still. Hit the back button and then go back in to check and the post(S) are there.
    Perhaps we should all just keep hitting “post” to see how many copies of a comment we can generate.

  25. @p (13) – Very well said. Thank you for posting. A few years ago when $MNKD was first going in front of the FDA, I asked a diabetic friend to give me a subq saline injection with a 31 gauge needle = painless. I tested my blood sugar = ouch. MNKD was solving a problem that doesn’t really exist.
    @Derek – Thank you for the link.

  26. Kazoo Chemist says:

    One final (for now) comment on the host. I decided to time my last post. It took 67 seconds for the posting to take hold and return me to the thread. No wonder so many people think that their attempts to post have failed and then they hit the post button once again. This is the only site I frequent that has this issue.
    Derek: don’t take this as a bash at you. I really enjoy your blog. It would just be so much better with a different host site.

  27. Kazoo Chemist says:

    Sorry, I just couldn’t resist relating the latest occurrence.
    I hit “post” for my last comment and set the iPad down. I came back in a few minutes and the iPad had put itself to sleep. I swiped the screen and entered my PIN and what was on the screen???
    “Gogardenclub.com”. No kidding!

  28. Mark Thorson says:

    I recall reading a study which found that inhaled insulin didn’t give very good control and wasn’t ready for prime time. I’ve got to start making dinner soon, so I’ll see if I can dig it up this evening.
    There’s been a lot of published literature on using inhaled insulin to treat Alzheimer’s Disease. Do a search on “intranasal insulin” and “Alzheimer”. Supposedly, receiving insulin via the intranasal route bypasses the BBB. I believe there’s a study which shows that — I’ll see if I can dig that up too.
    Although there has been speculation that bioenergetics is compromised in the Alzheimer’s brain, and it has been shown that insulin resistance occurs, it appears that glucose metabolism is not compromised and the notion that AD is “type 3 diabetes” is a pile of poorly supported speculation.
    If intranasal insulin is useful in the treatment of AD, it’s not because of bioenergetics. Insulin does more than signal tissues to absorb sugar from the bloodstream. There are pathways affected by insulin which are plausibly connected to the etiology of AD. As I recall, there are pathways which up-regulate the phosphorylation of tau. I’ll look for that tonight, but not now. I’ve got to get started on dinner for my mom (who was diagnosed with AD in 2011).

  29. Nick says:

    ITS UP 75% SINCE I BOUGHT IT 2 YEARS AGO AT 2.49

  30. Mark Thorson says:

    Here’s the study which I find compelling evidence that AD is not “type 3 diabetes”. Insulin resistance occurs, but glucose metabolism is not impaired. The relevant discussion begins on page 17.
    http://ibg.colorado.edu/pdf/Halter3_2012.pdf

  31. Mark Thorson says:

    Here’s a study which makes a good case for the intranasal route bypassing the BBB. In rodents, anyway.
    http://www.neurosurgery.uthscsa.edu/journal_club/journals/JOURNAL%20ARTICLES/Scranton_2011_rostral_migratory.pdf

  32. Mark Thorson says:

    Here’s a study linking insulin signalling to tau phosphorylation. It’s a cell study, so admittedly a thin reed on which to do more than idle speculation.
    http://www.jbc.org/content/287/42/35222.full.pdf

  33. Mark Thorson says:

    Older review of using intranasal insulin to cross the BBB for treating AD.
    http://www.biomedcentral.com/content/pdf/1471-2202-9-S3-S5.pdf
    If this stuff is so good, when will we see some big studies to nail down whether it really works? If there’s been a study like that, I must have missed it.

  34. LJSTewartTweet says:

    Derek. Time to get a better web site!
    A while ago you were talking about a move?
    Such a great blog deserves better.

  35. LJSTewartTweet says:

    Derek. Time to get a better web site!
    A while ago you were talking about a move?
    Such a great blog deserves better.

  36. Mark Thorson says:

    This appears to be the largest clinical trial of intranasal insulin for AD to date:
    http://www.kurvetech.com/pdf/an-intranasal-insulin-therapy-for-alzheimer-disease-9-2011.pdf
    I’ve just started looking at this study this morning. I’m not strong on statistics, so I’m wondering why they use a delta-log scale to display their results. One thing that raises an eyebrow is Figure 2A. Does the effect disappear at the higher dose? Or am I looking at noise?

  37. Anon says:

    If the prevailing sentiment is that injecting drugs frequently (several times a day in the case of diabetes) is not an issue, then why such a fuss about always making oral drugs? Understandable for the “lifestyle” drugs, but what about for other serious ailments?

  38. Anonymous says:

    #13p: “Inhaled technology solves zero problems a type 1 diabetic has. It prevents one from having to inject the insulin, which was never a big deal.”
    You should probably research a little more on inhaled technology before making a comment like that. Users have found it more effective at treating diabetes than with injections.

  39. Mark Thorson says:

    Looking at the Afrezza website, there’s not a lot of technical information there but there’s a picture of what appears to be an inhaler that you put in your mouth. It’s not intranasal, i.e. absorption via the nasal mucosa. It seems to be absorption via the lungs.
    Ooh, ah. I’m not sure that’s a good idea. I need my lungs for air. Don’t want to take too many chances with my lungs.

  40. Anonymous says:

    @13. Thank you for the post. I’m a Type I Diabetic of 29 years. I got it a few weeks before the Mets won the world series- boy how time flies 🙂 and with it comes technology. I started out on beef/pork insulin mixtures back in the day, probably moved to humulin in the 1990s. I never tested urine sugar, only ketones, but used these bg testing strips that we could cut into thirds to save money. You had to drop the blood on, time it, wipe it off, wait, and then compare it to a chart. Big error bars! To say the least. When I meet with recently diagnosed T1Ds, it’s interesting to hear them complain. It’s a lot easier now than it was back then, almost too easy. I’ve recently gotten on a medtronic pump and I agree that it is a godsend.
    I agree with much of what you’re saying so this isn’t a response as much as it is an add on.
    You’re right, there isn’t much of a draw for people like us, seasoned T1Ds, to get afreeza. I personally will never use it nor seek a prescription. But I don’t think afreeza was geared toward T1Ds. While we use diabetic products and will for life, we’re not the largest consumers. For example, I used to use Lantus and thought it was developed for T1D, but was surprised when I saw it marketed more widely to the Type II Diabetes crowd. People even give it to their diabetic dogs and cats! Early onset T2D is often controlled by pills, but can get out of control at times, necessitating a visit to the ER just for a shot of insulin. I see afreeza as the asthma-like inhaler for T2Ds. If BG >250 take a puff.
    Transitioning people to multiple daily injections also is not easy. Most T1Ds eventually figure it out, because its a life and death decision, but there are serious compliance issues in T2Ds when they start to require insulin. The health benefits of a non-injectable alternative will be enormous in this group. I can’t speak to this personally, but apparently afreeza can knock down a high blood sugar much more quickly than a shot of humolog. I can see a possible combined basal (lantus) + bolus (afreeza) regimen for early onset T1Ds, just to get them used to taking shots. As you say- the pump is great, but not everyone likes being attached to it and it’s not typically used when people are first diagnosed. I also don’t think it can be used during pregnancy.
    I know there was a lot of misplaced hype the past 30 years for a non-injectable insulin. They finally succeeded. I have no need for it, but I see a very large niche where it can be used, as our population ages and requires insulin supplementation.

  41. Jose says:

    Re Mark Thorson (#36): indeed, your alarm bells are well tuned. Reporting mean delta of a transformed change in response of a likely arbitrary scaled response, and lack of dose-response- all sketchy, and the scraping significance p-value, means likely clinically irrelevant and artifactual.
    Similar issues here in older work:
    http://w-ww.kurvetech.com/pdf/Neurology-Kurve-Insulin-Study.pdf

  42. Anonymous says:

    @38: I’ve not seen it. A1c levels are basically unchanged. I’m not saying inhaled insulin won’t work; I’m saying it is an entirely new way to treat the disease, which requires re-learning a lot of stuff, to achieve basically the same ends. No thanks.
    @40: That’s probably true. If it helps T2Ds, a) that would be great and b) that would be a much better market from a business perspective.
    Incidentally, do you know why pumps aren’t used right at the start for new T1Ds? I was really surprised to learn that.

  43. Anonymous says:

    @42
    I posted # 40.
    Re- why pumps are not used at the start.
    I think it depends a lot on the individual. T1D usually takes 2+ years to progress from diagnosis to full on insulin dependence/complete loss of beta-cell function. I remember taking one shot of long acting insulin a day the first year or two. A pump might not’ve been useful even if they were available. Shots are a cheap and easy way to get started and train someone to control the condition, usually done in the hospital. And hell, I took shots for 27+ years. I was counseled at times to consider the pump, but it’s not pressed as long as you have a regimen that works.
    It also depends on the endocrinologist. Some of them aren’t as up on T1D, being interested in adrenal, pituitary, thyroid, diseases, T2D, etc. that dominate their clinics and might not have a T1D diabetes educator in their practice.
    The pump requires education. Both from the supplier and a diabetes educator. It’s not foolproof. The sites can get irritated and fail. I wouldn’t recommend it to a swimmer or to someone who plays contact sports. It’s also expensive. I paid 2K after insurance for the device and there are quarterly consumable costs in addition to the insulin. I’ve met a few hundred T1Ds over the years. They’re a mixed bag. Some love the pump, some try it, hate it and go back to shots. Some don’t want to make the investment or fear being attached to a device for the rest of their lives.
    I’ve spent a little time seeing other patients in a diabetes clinic and in my opinion, compliance with shots in the borderline insulin-dependent T2D crowd is a problem. An inhaler would make a huge impact.

  44. p says:

    @43: Thanks. I took shots for about 25 years and loved the pump from my first wearing even though, like you, I was very reluctant. It’s kind of my thought on inhaled insulin. Once you have a regimen that works, reasonably well, there is a lot of inertia to changing it. Thus, unless you can tell me the outcomes for inhaled (or pump) will be much better, I won’t change.
    The pump solved a longstanding problem for me with morning high BG. I can’t see inhaled insulin fixing that without waking up at 3am for a snort.
    As I say, if inhaled works for T2D – bang, great product and worthy investment.
    By the way, post 42 was me.

  45. alexwolfe says:

    There may be some benefit to inhaled vs injection:
    am.aace.com/sites/all/files/Late-Breaking.pdf
    scroll to Abstract #1220
    REDUCED HYPOGLYCEMIA IS OBSERVED WITH
    INHALED INSULIN VERSUS SUBCUTANEOUS
    INSULIN ASPART IN PATIENTS (PTS) WITH TYPE
    1 DIABETES MELLITUS (T1DM)

  46. alexwolfe says:

    @23 “scientists often (but certainly not always) invent solutions without speaking to patients to understand the problem”
    Sure, but that statement is misplaced in this context because the person who founded Mannkind and invented Afrezza understands a lot more about Diabetes and the problems Diabetics face than most do.
    @13 does not represent the target market for Afrezza because he is on an insulin pump. Only a small fraction of Diabetics are on the pump (which btw the founder of Mannkind invented in the early 80s, later sold to Medtronic for $4 Billion).

  47. Toot Toot McBumbersnazzle says:

    @42 another reason you don’t start pump therapy right off the bat as a newly diagnosed T1 is you do need to know how to do multiple daily injections (MDI) – what if your pump fails on Friday morning, you won’t get a new one until some time on Monday. From Friday through Monday you’ll need to know how to (confidently) inject insulin…
    Also, pumps are absolutely used during pregnancy.
    My understanding is that Afrezza works faster than the current fast acting insulins (Novolog, Humalog, Apidra) and is out of your system faster. That’s a really nice draw…still wouldn’t use it.

  48. anonymous says:

    Wow. MNKD has doubled in share price since this article was published.

  49. Patrick says:

    Several years ago, when I was a research chemist and hearing about Affreza for the first time, if really seemed lIke a cruel joke to investors. I’m wrapping up medical school now amd have met a great number of patients (type 1 and 2) who are very hesitant to inject. These are patients that you would love to get below 8 or 9% HbA1C, let alone at goal. It’s these folks that make a good target. I’ve seen and used demos of Affreza and injectables,amd if you hate needles, it really is easy. It only comes in 4 unit increments, which is not helpful for a sliding scale or comfortable basal user, but the pk/pd profile looks even better than lispro. I don’t think anyone can say if it is a blockbuster, but I think there are too many uncontrolled diabetics and if it’s just too easy to use to say it is a bust.

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