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Business and Markets

Mannkind’s Last Stand

Back in October, I said that Mannkind (MNKD) “looks doomed”. To be honest, you could have said that about them and their inhaled-insulin drug Afrezza for many years, with a good chance of being right – I said it back in 2008, for example. And it’s not that I’m some sort of prophet. I mean, there have been so many things to doubt over the years that a person tends to lose count. I have to admit that I was amazed when Sanofi partnered with them on the stuff.

But as quarter after quarter has gone by, it’s become clear that Afrezza is not selling. It just isn’t. There doesn’t seem to be a market, which was the same problem that Pfizer discovered in their catastrophic experience with Exubera. Not enough people seem to want (or need) an inhaled insulin to make the development of an inhaled insulin worthwhile, and arguing with that proposition has been increasingly costly.

This morning, Sanofi terminated their agreement with Mannkind. The company is very close indeed to running out of money, and anyone who wants to go on with Afrezza is going to have to find a way to pay for a big post-launch safety trial. As Adam Feuerstein puts it in that link, “The financial challenges facing the company now are just about insurmountable“. But the MNKD cultists, some of them anyway, are still hanging on. I took a look through Twitter a while ago, searching $MNKD, and sure enough, there are people out there going on about how this is bullish news, Sanofi wasn’t even trying, Mannkind wanted to ditch them so that Afrezza could really take off, and so on and very much so on. The stock actually crept up a bit after the initial drop on the news. Idiotic conspiracy theories are already being proposed.

This is all delusional. (As Phillip II wrote in the margin of a report from one of his men that the Armada had actually survived and was regrouping to attack England, “Nothing of this is true. It would be well to tell him so”) It would be well if the people who are trying to convince themselves to keep buying Mannkind stock would give it up while they still have at least a tiny bit of their money left. It would have been better to have avoided the stock from the start, but the kind of person who wears an Al Mann t-shirt would surely have handed over their cash to some other lost cause by now, anyway.

Update: fixed the stock symbol. I’m going to blame that one on the fever I’ve got today. . .

Update 2: fixed the Phillip II quote, which my memory had slightly reworded. But since I last read Mattingly’s “The Armada” in 1982, I don’t feel that bad about it!

22 comments on “Mannkind’s Last Stand”

  1. Isidore says:

    No disrespect to Mr. (Dr.?) Alfred E. Mann intended, but in Googling his name by typing “Alfred E” brings up “Alfred E. Neuman” of “What me worry” fame as top choice. How appropriate!

  2. The behavior of Mannkind longs, though delusional, is also sadly predictable. For those interested in learning more I strongly suggest reading “When Prophecy Fails” by Festinger to understand the mindset. It takes incredible amounts of disconfirming evidence to force people to re-evaluate their beliefs. Often they believe in falsehoods ever more strongly after being confronted with disconfirming evidence.

  3. Mark Thorson says:

    Intranasal insulin is the next blockbuster Alzheimer’s drug!

    With the baby boomers aging, we’re facing a tidal wave of Alzheimer’s! And Afrezza is the solution! I see your strategy, Lowe. Talk the stock down, get it delisted, and when it’s a penny a share on the Pink Sheets move in big. Shkreli buys all he can, the stock surges to $40, and your $1000 investment becomes $4M. Too soon to move in now, of course, but I’ll be watching this too.

    1. BB says:

      Sounds like the script of “The Wolf of Wall Street”.

  4. PorkPieHat says:

    Mark Thorson

    I know you’re comments are tongue-in-cheek. But for others reading this, Afrezza is inhaled insulin, while the literature on insulin in AD is almost all using intranasal, which confers the ability to bypass first-pass effects through direct access to the brain compartment. I do believe that’s a real opportunity.

    What gets me about Dr. Alfred E. Mann is that he used to own an insulin pump company called MiniMed long before he started Mannkind. He should have known from that experience that it has never been a big deal to self-inject insulin. . .and its only gotten easier through the years. Add to that that Afrezza costs more, and it doesnt really work as well as injectable insulin (large PK variability), and you have to wonder, were they (and Pfizer with Exhubrisa…I mean Exubera) solving a problem that did not exist?

    Anyway, dude’s a billionaire, so Mannkind’s a bit different from other companies who’s cash flow is almost over…he’s invested some $250 M of his own money into the company. So, don’t really know if you can look at MKND like other public companies. I wonder how much upfront Sanofi gave them . . .

    1. Emjeff says:

      Porkpie, you don’t know much about pharmacokinetics. Both inhaled and intranasal insulin ” bypass first-pass effects” , so there is no difference between the two dosing paradigms in that respect. You also don’t know much anatomy- the nasal passages do NOT offer “direct access” to the brain.

      1. Ann O'Nymous says:

        Gosh darn it, all that money spent snorting cocaine and nothing but a runny nose to show for it.

      2. NJBiologist says:

        Emjeff–Particularly among the peptide therapeutics crowd, intranasal dosing is seen as a way to get drugs absorbed rapidly. The mechanism calls for rapid absorption from the sinuses into olfactory neurons, which don’t have much of a barrier between them and the outside world, and from there into the brain. I’m not sure the data are as strong as the real enthusiasts of direct absorption think, but there’s definitely some room to argue that intranasal dosing results in improved bioavailability of peptides, particularly in the brain.

  5. anon says:

    The question that always comes to my mind when I hear about inhaled insulin is “Why don’t people want it?” Maybe I’m completely missing something, but why don’t people who have to inject themselves with insulin daily not want to just inhale the drug instead?

    1. Gretchen says:

      Anon: because (1) it’s much more expensive, (2) no one knows the long-term effect of inhaling insulin on lung function, (3) dosing isn’t as accurate, and (4) injections are not a problem except in some needlephobics.

    2. Hap says:

      I don’t have diabetes, but from what I’ve read here, the problem is not insulin dosing but glucose monitoring – the needle stick to monitor glucose concentration is much more inconvenient than the administration of insulin. Hence, injecting insulin isn’t much of a hindrance to patient compliance (for type I) and paying more for inhaled insulin (or suffering added side effects from it) doesn’t really make sense. It might be worth it for type II diabetics who need insulin, but apparently not (either no evidence or not enough value).

      1. tangent says:

        “I don’t have diabetes, but from what I’ve read here, the problem is not insulin dosing but glucose monitoring – the needle stick to monitor glucose concentration is much more inconvenient than the administration of insulin.”

        Exactly — from the diabetics I’ve known, the insulin needle is nearly painless, but the lancet for monitoring, that stings.

        The insulin needle is about 30 gauge (~300 μm external), a finger lancet is like 22 gauge (about twice the size). And worse, the lancet hits a richly-innervated finger pad.

  6. Mark Thorson says:

    By the way, it’s MNKD, not MKND. Closed down 48% on nearly 8X the normal volume.

  7. Eric says:

    The Philip II quote is lovely, can you point me to a source? The Web is not being helpful.

    1. Derek Lowe says:

      It’s from Garrett Mattingly’s “The Armada”:

      It’s probably not showing up because I hosed up the quote a bit – I’m going back in to fix it.

      1. Eric says:

        Thanks! (And now I’ve ended up reading about the Spanish Armada, let no-one say this site isn’t educational.)

  8. J Tyson says:

    I’m not sure why you give Feuerstein the dignity of mention: The guy works for a boastfully-admitted stock manipulator:

  9. idiotraptor says:

    I am a life science PhD who has worked 20 years in both biophama and academic research as well as, a person with IDDM for over 40 years. Hap and Gretchen’s comments above succinctly identify the critical issues. The value proposition (convenience/safety/efficacy versus cost) simply isn’t there for the inhaled or the nasal-spray insulin.

    At least the Afrezza delivery device doesn’t resemble the sex toy-like Exubera dispenser….

    1. steve says:

      That may be a disadvantage. Think of the potential sales – it’s a sex toy, no it’s a drug delivery device. Stop, stop, you’re both right!

      1. Mark Thorson says:

        The Afrezza device has been described as “bong-like”. I wonder if it would make sense to combine Afrezza and nicotine. That would ensure regular compliance — when your nicotine level got low, you’d want another hit.

        It used to be thought that nicotine was responsible for the temporary vasoconstriction and blood pressure rise that occurs when smoking a cigarette. A recent study shows this is not so — when compared against transdermal nicotine patches producing the same blood level of nicotine, there was no vasoconstriction. The culprit must be some other component of cigarette smoke. Nicotine actually seems to be quite benign — it doesn’t cause the cancer or cardiovascular risk from smoking cigarettes. It’s just addictive, and that might be useful in some drug dosage forms. Especially ones which have poor compliance, like anti-schizophrenia drugs. Chlorpromazine plus nicotine, anyone?

        1. tangent says:

          “Chlorpromazine plus nicotine, anyone?”

          Nicotine dosingapparently is self-medication for some schizophrenia symptoms, too, so it’s a glorious plan.

          (Well, except for the issue that you’ll inevitably get patients overdosing on their antipsychotics to get their nicotine, if your plan works, or you’ll just get them vaping, and it won’t. Too bad.)

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