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Synopsys Inc. Message Board

lakers_w 382 posts  |  Last Activity: 2 hours 9 minutes ago Member since: Jun 13, 2000
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  • Amy Tenderich - Driving New Inhaled Insulin Afrezza

    I have been using Afrezza, the new inhaled insulin developed by MannKind and marketed by Sanofi, for the last three and a half weeks.

    So far it’s… mysterious and exciting. Mysterious because the dosing seems ridiculously imprecise compared to the micro-unit counts I’m used to with an insulin pump. And exciting because I’m finding that Dr. Steve Edelman was right – this stuff really does work extremely well! I don’t think I’ve seen such a lovely lack of glucose spikes since around the end of 2004, when my diabetes honeymoon officially ended.

    Other major benefits of taking Afrezza as an insulin-pumper I’ve discovered are:

    -I feel relieved from the constant pressure to be exact in carb counting (see details on dosing below)
    -Likewise, I’m relieved from the guessing-game known as IOB, or Insulin on Board, that can have unwanted impact up to four hours after taking a subcutaneous bolus dose
    -I can eat more spontaneously (or rather achieve better BG results with spontaneity) because Afrezza is best taken at the very moment of food consumption, or even afterwards if your starting glucose is less than 120
    -Taking less insulin through the cannula seems to be relieving my skin of some of its grief from overuse/ irritation / lipohypertrophy

    Let me put it out there: I hope this is more than a test drive. I hope my insurance company plays along so I can stay on this stuff!

    Handling the Inhaler

    It’s a funny little thing, this inhaler. My family giggles every time I use it, because yes, it’s reminiscent of sucking on a little ganja pipe (thanks, Shutterstock). Sometimes you can feel a scratchiness on your tongue as you inhale – like the powder passing over.

    In training, I was told you have to hold it very level, and be careful not to turn it around or even jiggle it once you’ve placed a cartridge in and pressed the top down – otherwise you run the risk of losing some of the powder. They say you should inhale normally, but I’ve found that if I don’t suck my breath in hard, some powder residue does remain in the cartridge or sprinkle out of the device right after use.

    You’ve probably heard that Afrezza comes in 4-unit (blue) and 8-unit (green) cartridges. If you run into any red cartridges, note that those are blanks, for demonstration purposes only. The whole product comes packaged in a box with two foil-sealed sleeves of cartridges and two inhalers, which are meant to be disposed of after two weeks, as residue build-up may block dosing after that amount of time.

    The packaging insert instructs you to keep the cartridges stored in the refrigerator, other than the amount you need to carry around for present use. During training, the Sanofi rep told me that just like with liquid insulin, extreme temperatures can render it ineffective.

    ‘Block Dosing’ & Tweaks

    My doctor started out recommending that I use Afrezza to cover meals only. But I quickly found that was confounded by giving correction doses on my pump, which were often still active in my system when mealtime came -- so it would be impossible to judge the effect of the Afrezza on its own.

    So we agreed I should start using Afrezza for both mealtimes and corrections, and that’s when things started getting good. I started seeing pretty flat lines on my CGM, often not exceeding 160 after a meal, and when needed, those Afrezza corrections kick in fast! (within 1.5 hours latest). I found I could watch my 220 melt away before my eyes.

    The extremely weird part is the unfamiliar “block dosing” as I call it. As a pumper who’s used to relying on a Bolus Wizard to set precise doses of 3.25 or 5.5, what the heck would I do with just two set options of 4 or 8 units? How could that possibly cover my carbs correctly?

    Turns out, this simplicity is one of my favorite things about Afrezza. My doctor started out by suggesting that I dose one 4u cartridge for any meal less than 40g carb, and an additional 4u for over 40g carb. However, we noticed that I was often on the upswing after a meal and would have to keep correcting, therefore we lowered the threshold to 30g carbs.

    I eat pretty low-carb, mind you, so I rarely take more than 4 units at a time. But I did notice that when I do eat higher-carb choices, I seem to need even more Afrezza than suggested, and definitely more than I would use with subcutaneous insulin.

    Exercise and Micro-Corrections

    Two things I’m still figuring out are exercise, and what to do about “small” corrections when I’m only at 150+ and want to come down a bit without going hypo.

    Regarding exercise: the most difficult change in mentality is a new a view of IOB – how long does Afrezza really stick around in your bloodstream? Not very long, it turns out. Which is a good thing!

    I’ve found that my previous temp basal settings are no longer useful, because they were accounting for at least some residual IOB from my breakfast dose. That is, I mainly work out in the mornings and would reduce my breakfast bolus by 50% in advance of the temp basal I’d use for my workout.

    “Now, if I have no choice but to take those 4 units of Afrezza, what will happen during my aerobics class? What should I do?”

    That was a frantic email I sent to my doctor, to which she replied: “Probably 0% (temp basal) for one hour after the Afrezza dose, then 50% for as long as you normally would decrease it. If you'd prefer to try something else, go ahead, but have high index of suspicion for hypos and be prepared.”

    So far I only had one exercise-related hypo, and that was when I took an Afrezza correction at the very end of a gym class, and then didn’t end up eating lunch for a while. I guess getting that Afrezza blast while I still had 15 minutes of hard exercise ahead of me wasn’t the best idea.

    In terms of making corrections when I need just a small adjustment, like from 145-160, my doctor’s encouraging me not to go back to taking corrections on the pump, which will stick around too long and complicate things. Instead, she’s suggested I try a dose of Afrezza when I’ve been at 150+ for at least 2 hours since my last meal dose – but “at a time when the family is home with you and you’re all alert for possible hypos.” We'll have to see how that works.

    I sure do wish Afrezza also came in 2-unit cartridges, to be able to make these small corrections without having to worry about going low. Meanwhile, my endo and I are still experimenting.

    Nevertheless, I can tell you that my numbers – and CGM lines – have been greatly improved in the last weeks.

    Got Cough?

    My doctor keeps asking me about this, as apparently it’s been a thing for a number of new patients. So far I mainly feel a dryness and scratchiness at the base of my throat – so that I feel the need to clear my throat often.

    Some fellow Afrezza users on Twitter have suggested gargling with water, and/or drinking a glass before or after dosing. Thanks for this and several other tips, D-Peeps!

    My doctor also suggested a product called Biotene for dry mouth. Haven’t tried that yet.

    Afrezza Frenzy

    Finally, I wanted to note that few new diabetes products that have stirred up such a frenzy of investor stalking and patient debate as Afrezza already has. I tweeted recently about the fact that I never had to block any followers on Twitter until I started mentioning #Afrezza.

    Here’s the deal: there are Bulls and Bears on both sides of this product. Many have criticized original @Afrezzauser Sam Finta as being a shill for Sanofi and MannKind.

    I can honestly say that I was VERY SKEPTICAL myself of this new inhaled insulin. But I’m just keeping it real: so far the stuff’s worked very well for me, and I’d like to keep using it – as long as my scratchy throat and insurance company play along.

    More updates to come as we all gain more experience with Afrezza.

  • From: Kyle Daniels
    Date: Wednesday, March 11, 2015 at 12:13 AM
    To: Bruce Bode
    Subject: Re: Afrezza

    Dear Dr. Bode,

    I just finished read Sim Finta’s twitter account and he mentions that his built-up insulin resistance has been reversed. He has been back on Afrezza for 2 weeks and stated that this was confirmed at his Doctors appointment.

    Is this true? How can this be possible for a Type 1 diabetic? I have never heard of something like this being one myself. Is Afrezza really the real deal?

    Thank you!
    Kyle.

    ———————————————————————————–

    From: “Bruce Bode”

    Date: Mar 12, 2015 12:22 AM
    Subject: Re: Afrezza
    To: “Kyle Daniels” (and several others)

    Glucose and lipotoxicity occurs regardless of the type of diabetes; glucose does not know if the patient is type 1 or type 2. High Glucose and High FFA and other factors impair insulin action as well as insulin release.

    We see this phenomena all the time in new onset type 1 diabetes; They go into a honeymoon upon treatment of insulin due to breaking both glucose and lipo toxicity. This may last months or longer.

    Sam’s A1c was above 10% with marked variability with now a mean glucose of 95 mg/dl with a SD

  • en.sanofiDOTcom/Images/38551_Letter_to_shareholders_N40_EN.pdf
    SANOFI - 40th LETTER TO SHAREHOLDERS Has full page Afrezza Ads to tens of million investors.
    Need Dr Bruce Bode, Sam, others' articles published on NE Journal of Medicine, Journal of Diabetes, and more trade journals. Hundreds of thousands GP, Endo, Nurses, Clinical Tech will learn it - the fastest way to win mind shares.

  • Also we will see sales increases on our insulin API business due to our sales to MannKind. As you know, we have a contract with MannKind where we will supply them with insulin for their Afrezza product. And that contract has minimum purchase quantities at fixed prices. The majority of our insulin sales in the fourth quarter were to MannKind, and it should be noted that these sales in 2014 count toward their 2015 minimum. Remember that the MannKind contract, like most of our insulin contracts, are denominated in euros because nearly all of our expenses for that business are also euro-based, as are the payments that we make to Merck as part of the purchase price for that business.
    We had previously estimated that we would see approximately $32 million in sales per year for MannKind, but due to the declining dollar versus the euro, the dollar value of sales has declined closer to $25 million per year. Likewise, our expenses and payment obligations to Merck have declined by the same percentage.

    Bill reported, enoxaparin pricing continued to decline; however, we expect this decline to be more than offset by strong growth of our other products and our insulin sales to MannKind.
    In the fourth quarter, we scaled up production at our French subsidiary AFP to meet MannKind's demand for recombinant human insulin API. I'm happy to report that we're now selling such API to MannKind, and although the value of the euro has declined since signing the agreement with MannKind, all of our costs at AFP are in euros, as well as our payment obligations to Merck. Therefore, as Bill discussed, we have a natural currency hedge in place.
    Additionally, in January 2015, we entered into a supply option agreement with MannKind, pursuant to which, MannKind will have the option to purchase recombinant human insulin API in addition to the amounts specified in the July 2014 supply agreement. Under the option agreement, MannKind has the option to purchase additional insulin API in calendar years 2016 through 2019. In the event MannKind elects not to exercise its minimum annual purchase option for any year, they will pay us a capacity cancellation fee

  • The Inside Truth about Exubera and Afrezza

    For years, I’ve been saying the only thing in common between Exubera and Afrezza is that they were both inhaled. I recently decided to talk to the real experts about this issue-two people that have been on both insulins! They happen to also be in our Afrezza User Challenge to “Stay in Zone” and have firsthand experience with Exubera (which has been a perennial comparison for Afrezza), so I wanted to take the time to ask them some tough questions (separately) that I’m sure we would all like to know. What they said was more than I have ever learned from any other article.

    The two individuals are L=Laureen (T1D since 1983) and B=Brian (T1D since 1999) and they had a lot to say about their experience and opinion of Exubera and Afrezza. This is where our interview begins.

    Background Info: What was the deciding factor for you to begin Exubera, and how long were you on it for? Was it an easy transition for you?

    (L) For me the deciding factor was reducing injections and gaining better control. In my lifetime, I have done over 100,000 injections, so having another way to administer a drug I needed to live was fantastic. The first 4-6 weeks took adjusting. Mainly because Exubera was dosed in mg and no doctor ever dosed insulin that way. Exubera also made my long acting (Levemir) more effective, so I had to reduce my basal level. I was on Exubera for 2 years.

    (B) I started taking Exubera because I hate to take shots. I took Exubera from its launch until about 2 1/2 years after it was discontinued. It was a very easy transition from injectable insulin. Inhaling insulin is WAY easier and WAY more convenient than injecting insulin.

    What was your experience with Exubera: the 3 best things and the 3 worst things?

    (L) Best

    Ability to take insulin anywhere without the stares of needle phobs
    Amazing control it gave me and reduction to one injection a day of Levemir
    Lower HgA1c
    Worst

    Size of inhaler – I had to buy a larger purse to carry around, a small price to pay, but it was gigantic
    Determining dosage in mg
    Adjusting back to Novolog once it was pulled off the market and my supply ran out
    (B) Best

    No shots for fast acting insulin.
    Super easy and convenient to use. could throw in car and go, take doses while driving.
    Can easily take multiple doses of insulin to adjust and correct, instead of a giant single dose like with injectable insulin.
    Worst

    The inhaler was very large.
    People would think it was a Bong. Still was quick to use, so could do it more discreetly than a shot.
    The properties of the insulin was lacking.
    How did you feel when Exubera was pulled from the market, what did you do?

    (L) I cried; I was absolutely devastated. I could not believe a drug company as large as Pfizer only gave this new drug a matter of months to take off. How could you expect to see sales with no advertising and when doctors didn’t even know about it. Exubera was my cure. As a type 1 diabetic, I don’t anticipate seeing an effective artificial pancreas or non invasive way to provide me with the insulin I need just to stay alive. Exubera gave me the freedom to feel like a normal person and inhale when I needed to without another injection. Injections keep my alive, but a world without them is one I didn’t think I would ever see, until Exubera.

    (B) I felt completely outraged, it was not given a chance or enough time to succeed. It would have helped a lot of people with their control of diabetes. My wife called Exubera and complained. During their last week of business a 2 1/2 year supply showed up on my front porch.

    What was the deciding factor to try Afrezza? How was your transition?

    (L) I have been following Mannkind and Afrezza (formerly Afresa) since 2009, when Exubera was pulled off the market. I emailed Matt Pfeffer, from Mannkind, to get information on trials and FDA approval. In 2009-2010, Afrezza was in very early stages so I continued to follow it through the trials and FDA denial, then subsequent approval. I took trial information to my physician and as soon as it hit the market, I said, I want it. As with any change in medicine, there is a transition period, but so far it has been good. Determining proper dosing on Levemir and carb to Afrezza ratio has been the biggest challenge; but, I have found transitioning to Afrezza has been painless. The biggest issue so far is getting enough supply as to not run out.

    (B) While using my 2.5 year supply of Exubera, I heard about Afrezza. I hoped my Exubera would last until Afrezza launched. Of course that didn’t happen, but it did allow me to follow Afrezza and be prepared for its launch. The transition this time was remarkable. In just 2 or 3 days I could see that I was going to have great control. I couldn’t believe how well it worked. I just wanted to not take shots. I knew from Exubera inhaling insulin is easier, I knew I would have better control but I had no idea my control was going to become ground breaking.

    What has been your experience with Afrezza so far?

    (L) Best

    Afrezza works instantly. I have checked my blood sugar every 10 minutes after inhaling and eating to show no, I mean NO spike in BS, at all.
    The life of it – since it is in and out in 1.5-2 hours, it makes life so easy. I don’t have to worry about if I still have Afrezza left from a previous dose (like I did on Novolog). I can eat a snack, like a normal person, and inhale Afrezza with no worries about a tail end overlapping and bottoming my BS out.
    The Dreamboat – it is an amazing device. I am a woman, and we have very small pockets in our pants, but Afrezza slides right in!
    Worst

    Insurance coverage – This drug is FDA approved and the pre-authorizations and not getting comparable coverage to a bottle on insulin is an absolute crime.
    Did I mention insurance coverage?
    Medical professional’s lack of any actual data on this medicine. I have “argued” with Pharmacists and Doctors about the misperceptions they have on it because they are not educated. I get very frustrated when people say bad things about it with no solid data to go on.
    (B) Best

    The insulin itself works remarkably well. It has the ability to stop BG from rising. I can eat anything I want and it just wont allow my BG to rise, or rise very little. On the other hand if I do have a BG reading higher than I like it lowers my BG very gently. It took me while to figure that one out. People say 4 units is too much if your at 130, but that’s not true. Afrezza works so fast and stops working so fast 4 units just gets your BG moving down, by the time your at 100 its all done working.
    Super easy and convenient to use. I can use it any time, anywhere. I can take a dose while driving alone down a winding road in the dark. Its too easy, and the inhaler is super small. I do it right in front of people all the time and they don’t think anything of it. It attracts 0 attention.
    Taking multiple doses is huge. With shots you have to guess how much your going to eat, how much you plan on exercising, your current BG and if its rising or falling, then take your best guess at how much to shoot up. With Afrezza because your inhaling it, you can take a smaller dose, then take more later, as often as necessary. All the people I know who take injections try to do it in one dose, and if they didn’t guess their dose just right they tend to wait until their next shot. This makes them high for a long time. The body does not digest all Carbs at the same rate, so taking multiple doses makes more sense to coincide with digestion.
    Worst

    The only bad thing I’ve experienced is that for some reason there are folks out there determined to bash it. It doesn’t matter what evidence I provide, they have made up their minds to be against it. It’s a new drug, people are just starting to use it. How can you be against something that hasn’t had a chance to prove itself. It’s like they are walking up to a person who is 6’6 and saying they don’t think they can play basketball, without ever seeing them play…In my opinion its like they’re saying it to Michael Jordan!
    How do you think Exubera and Afrezza stack up against one another—are they comparable and is it a fair comparison?

    (L) This is difficult as they are different drugs. In general they appear to be comparable, but the advantage of Afrezza is the “quickness” of it. It is in so quickly and out quickly after covering food and never increasing BS. Exubera stayed in a bit longer and I would have to think more about if I had a tail left before inhaling more. The other glaring piece to me is the powder in Afrezza is much more effective. With Exubera, I took 7mg at a time. The mg comparison to what I take with Afrezza is 1.4mg (for 2, 8 u cartridges). So you need a lot less powder than with Exubera.

    (B) It’s not a fair comparison, they are similar in how easy they are to use and the fact that you can take multiple doses. I don’t get real bent out of shape when they are compared because Exubera would have helped people. The decision to pull it off the market was the cause of its failure, otherwise it could have been successful. On the other hand Afrezza would have caused its demise due to the fact that Afrezza works so much better.

    What would you say to someone who was on exubera and now thinking about taking Afrezza?

    (L) Do it. Don’t ask your doctor, demand a sample to try it. It will change your life. If your doctor says no, find a new doctor. We must be in charge of our own health and if a doctor refuses to look at the data and see how this is changing lives, then a new doctor is in order.

    (B) Do it!

    How long have you been on Afrezza and what is your opinion-has your life changed at all—can you give a few examples?

    (L) I am going on 4 weeks. I had a sample pack then ran out and had to go back to Novolog for a week before I could get re-supplied. The instant effect of Afrezza on food intake is amazing and honestly unbelievable. If I didn’t check my BS so often to prove it, I wouldn’t believe it myself. I was 93 at dinner, ate pasta and had a glass of wine, inhaled 2, 8u cartridges, and one hour later, 90, 2 hours later, 105. There is no spike in bs. I am a normal person!

    (B) I started Afrezza about at its launch, within a few days. Has my life changed? Ya, bigtime. My pre Afrezza A1c was 10.1. My first A1c on Afrezza only I expect to be around 5.5. I’m no longer sick from Diabetes. With Afrezza I don’t ever have high BG anymore and I don’t have lows either. I don’t consider myself a diabetic anymore. Not health wise anyways.

    What do you think is keeping most doctors from prescribing Afrezza? How encouraging and knowledgeable was your doctor to prescribe it?

    (L) Doctors are confused about the dosing as well as prescribing info. I went to my doctor with the information and told her I wanted it, but she wasn’t sure how much I should use and was confused about only 2 options for dosing. Now, those 2 options work very well, but there needs to be better education on the pharmacology to physicians and pharmacists. I had been bringing my doctor information on it for 2 years. She was knowledgeable about it, but leery of the dosing.

    (B) My Dr. knew about it because I called her the first day I heard about it a few years ago and I have been waiting ever since. I forced the conversation. I spearheaded the Dr. to learn about it. I was crushed a couple weeks ago when my cousin who is a T1 came back from her Endo appointment and told me her Dr. wouldn’t prescribe it to her. Her Dr. told her it’s only for T2’s and that I must be a T2 or else I was misdiagnosed. I would laugh at that, except for that Dr. compromised my cousins health and made statements that are way out there. I’ve been a T1 for 16 years by the way. I think there is a total meltdown in regards to Dr.s and their current knowledge and understanding of Afrezza. This is a area that needs to be addressed and fixed .

    Having taken both, what would you tell everyone? What are you going to tell your doctor when you see him next? and what is your recommendation about Afrezza-do you think it will be a success or go the way of Exubera?

    (L) Afrezza is as close to a cure for Type 1 diabetics as we will ever get. I get there are insulin pumps, but I refuse to walk around with a tube attached to my body all day. If you are type 2, and didn’t want to take injections, then you will love this. This drug is amazing, it gives you freedom and peace of mind. My doctor will hear all about my great blood sugars. I will also tell her to give my contact information out to others who want a firsthand account of it. Exubera being pulled devastated me, so I only hope that health care professionals, Insurance Companies and Physicians open their mind to a non-injectable form of insulin. Once they see the real life results, they will see there is more than one way to manage this disease, a much less invasive way.

    (B) I’d tell any diabetic to consider it or better yet, try it. It doesn’t work like any other insulin, so it really can’t be compared to other insulins. If diabetics try it I am convinced they will have results just like mine.When I see my Dr. next time I’m not going to say anything. She will read my graphs from my CGM. They speak for themselves. So will my A1C. I think Afrezza will be a success. With Exubera we didn’t have CGM,s to prove the results, it didn’t work even close to how well Afrezza works, and there was no social networks to share the data. Nowadays I can post my results online in a minute. Others can see the results nearly real-time. I have a lot of people interested in it. I know the demand is there. The two biggest hurdles Afrezza faces is lack of Dr’s who are knowledgeable, and lack of insurance that covers it appropriately. Right now the only people using Afrezza are the ones who demanded it and went through all the work to get it. It shouldn’t be that hard to get. My Dr. was totally onboard with it and my Insurance also covered it prior to launch, and yet it still took many phone calls from me to my Dr. to my Insurance and to my Pharmacy to get the Rx written by Dr. just right so the insurance company could cover it and the Pharmacy could order it. This is a issue that needs to be fixed.

    Anything you want to say/add not asked or covered?

    (L) Fight for what you want and for what works for you. Write to medical directors and go through appeals processes because this drug is worth the fight. This is your life, your body and you have to live with any complications so do not let anyone tell you this drug doesn’t work. It does, I can prove it.

    (B) When you have control of your diabetes, your life does change. Your health gets better immediately. Afrezza will give Diabetics total control of their BG.

    Thank you so much Laureen and Brian for sharing your experiences and opinions with me and also the world. Grateful for all you are doing for diabetics everywhere and also taking control and going on the “offensive” against your diabetes to have a longer and healthier life with your family and friends. Wishing you both an easier journey now that you have Afrezza.

  • ir.amphastarDOTcom/events.cfm

    Amphastar Investor Presentation April 2015 pdf file, slides 9, 14, 15 of 25

    Apr 15, 2015
    12:10 PM ET
    14th Annual Needham Healthcare Conference Webcast

  • Mgmt wouldn't want to incure SH's wrath on 5/21/15 or 5/5/15 ER. Hakan and Sam will be interviewed by TUDiabetesDOTorg on 5/7. SNY announced Afrezza launch 2 days before 4Q14 ER. Simple psychology!!

    1. SNY: Inhaled GLP-1, Oxyntomodulin Obesity, oncology MKC1106-PP for prostate, MKC1106-MT for advanced stage melanoma

    Read YMB:

    "NIH, 2015 "Environmental Biomedicine" Book: MNKD TS/GLP-1 Clinical Trial"
    "ADA: Pulmonary Administration of GLP-1 Technosphere® Powder Elicits Dose-dependent Insulin Response"
    "Mnkd's Netherland Secret Clinical Trial of TS GLP-1 MKC253 Inhalation Powder revealed"
    "Technosphere/GLP-1 Patent filed 3/19/15"
    'A Study Designed to Determine the Safety and Pharmacological Response of MKC253 Inhalation Powder in Adults With Type 2 Diabetes Mellitus"
    "Technosphere/Oxyntomodulin Obesity Patent filed Mar 19,2015"
    "MNKD oncology drug candidates, MKC1106-PP for prostate, MKC1106-MT for advanced stage melanoma (in phase II study)"

    2. GSK: Inhaled Imitrex, Zofran

    "Inhaled Migraine Imitrex, Nausea ZOFRAN.
    GlaxoSmithKline drops plan to sell off older drugs business"

    "Griffin Securities on 3 TS apps"

    3. Lilly: Inhaled PTH Forteo , IBS, Trulicity

    "Clinical drug delivery has been demonstrated w/ PTH/Technosphere"
    "Lilly could license TS to protect PTH Forteo $1.3B, GLP-1 Trulicity $1.4B"
    "Connecting The Dots Mannkind + Rose Pharma + Lilly = Lilly Could Be Mannkind's Next Major Partner For IBS"

  • Phase 3C – Market Approval and the Soft Launch

    For years we have followed the logical progression of products through clinical trials and into launch and commercialization. The approval of an NDA is also known as “marketing approval” and is usually followed quickly by launch—also known as commercialization. Launches are usually treated as an event, often signaled by a “launch meeting” in which we fire up the troops, provide some high-level training, and rally ‘round the flag. Lately, however, the launch process for many products seems to have sputtered, with the excitement inside the launching company unmatched in the marketplace. Many sales teams feel rejected when the market doesn’t jump to embrace the product, and these same salespeople often feel let down by their company and their colleagues in marketing. True, there have always been failures in pharmaceutical markets, but why is it becoming so much more common? The simple answer is that the market has changed.

    Over the past several years three forces have aligned to make the successful commercialization of new pharmaceuticals more difficult: the crowding of therapeutic categories by more new (and not so new) products, the rise of third-party payers, and some spectacular product failures. These forces are not independent: they interact and each, in fact, magnifies the power of the other.

    CROWDED CATEGORIES

    Whether we blame “me-too” drugs, the lack of innovation and inspiration, or whatever, there is no denying that most therapeutic categories are becoming more crowded. This is not new; in fact I wrote a paper about it in 1995.1 At that time, though, new competitors were often likely to offer real improvements, either in efficacy or tolerability, and were readily accepted by the market. What is new now is that we have more products that do not offer substantial new benefits; they simply provide more options. The value of Zantac over Tagamet was fairly easy to establish (I know this is ancient history to many but the point is important), and the value of Lipitor over Zocor was enough (at that time) to convince more doctors to prescribe the newer drug. But as we look to our crowded categories today, it is often much more difficult to identify the meaningful differences among products—certainly, product teams and their agencies will attempt to point out any differences, but in most cases the market does not appear to appreciate them.

    I’ve often talked about understanding market opportunity in terms of “receptor sites,” as in, “Are there enough open receptor sites in the market for your product, or are they already occupied firmly by another product?” We can see in the listing of NDA approvals that there are more “repurposed” and reformulated drugs and fewer priority reviews (other than in oncology), which means that fewer truly innovative medicines are coming to the market. This isn’t a criticism of pharma R&D, just an acknowledgement that it is less common—and perhaps more difficult—to discover and develop truly innovative and needed new drugs. Although your new ADHD product (or antihypertensive or other category) may be special to you, if the market doesn’t see the product fitting a specific unmet need it is unlikely that there will be much use. In many categories, it appears that new products are not offering new value, but often only offering another choice. That offering of another choice—without new value—shifts power from the marketer to the customer, which brings us to the next force.

    THE RISE OF THE PAYER

    For more than 20 years, I have heard people talking about how powerful payers are becoming, and for close to 20 years my response has been: “Oh yeah, when?” I now have an answer to that question: “Right about now, depending on the category.” Payers are using their muscle and influence in markets as never before, but they really couldn’t do this until they were provided with more products that allow them to play one against the other without denying physicians the ability to treat patients effectively. The inevitable result of a crowded category without substantial and meaningful differentiation is price competition, and payers know this and use it to their advantage.

    The first stage of management is, in fact, non-management. At launch, virtually all new products will either be placed on third tier, a co-insurance tier, or be not covered. In over 99% of cases, this is a policy decision that has nothing to do with the product or its price. This allows the payers to evaluate the product and its use before making a formulary decision—but it also acts to slow the adoption of the product. Medicare Part D requires a “review” within 90 days of commercialization, but that “review” can be as simple as a decision to keep the product on a high co-pay tier for another year before making any other decisions. If you are fortunate enough to be launching a new product that meets a gaping unmet need in a critical area, your product may be reviewed fully and more quickly, but that’s the exception not the rule.

    In my conversations with payers, which occur at least once per week, the one constant theme in the “rule of management” is that when there are four or more agents in a category, it is a target for management, and when there is at least one generic in the mix, it becomes a very attractive target. “Management,” in this case, may range from simply placing some products on higher or lower co-pay tiers to the imposition of prior authorizations or step therapy (also called “generics first”). Many categories (such as contraceptives) are “managed” in this manner: some call it a “first and third” approach, with all generics on first tier and all brands on third. Whatever the form of management, what makes it possible is the presence of similar competitors—payers love “me-too” drugs because they help them do their job! Payers, in general, are feeling and acting more powerful because so many categories have so many therapeutic choices. In a category with several similar agents, physicians are unlikely to fight for one product over another, and this phenomenon builds on itself because the more “power” physicians give up, in terms of product choice, the more they tend to be willing to give up in the future, as long as patients aren’t harmed.

    Thus more choices for the physician has resulted in less autonomy for the physician and more choices being made for them by payers—regardless of the effect on your product and your plans, you must at least appreciate the irony!

    PRODUCT FAILURES

    There is at least one more reason for physicians to be slow in adopting new drugs. Without going into detail, in recent years several major products have been associated with potentially dangerous sideeffects, and many have been withdrawn from the market. We’ve noticed an increased reluctance among primary care physicians to try many new chemical entities (NCEs), because they were unfamiliar with them and chose to let others gain experience before taking a chance on new drugs. This, too, has helped payers to gain more confidence: they determine their need to cover a drug, in part, by assessing physician demand, and have justified their delays in reviewing new products by their need to assess physician uptake. With many physicians unwilling to risk an early adoption of NCEs, payers either deny coverage for many new drugs or place them on their highest co-pay tier—both actions reduce the value of a drug to the physician because they result in higher patient costs. With the availability of so many good—or at least adequate— therapeutic choices for so many disorders (e.g. fewer “receptor sites” in the market), there is less urgency within the market to adopt new drugs. Not that this is true in every case, but for most new drugs there is little urgency within the market to adopt new therapies because there are so many good options.

    THE SOFT LAUNCH

    NDA approval, also called “marketing approval,” once marked the beginning of the formal launch of a product, its “birth” if you will. Today “marketing approval” is fine, but unless the new product is a significant breakthrough that will find a ready market just waiting for it, your new offering will likely require “market approval,” by way of formulary coverage decisions and some level of trial and approval by practicing physicians, before it can truly be considered launched. Think of this as an “incubation period.” NDA approval, rather than signifying the end of the pre-launch process, now may signify the beginning of a new final stage of the pre-launch process, the “soft launch.” During this stage, you fine-tune your approaches to the various market participants, help them understand your product and have them help you understand the way they see it, and then finalize your actual marketing plans. This will affect forecasts, budgets, and virtually every aspect of marketing planning, and those who don’t build these new forces into their plans are headed for some big disappointments in the near future.

  • Mannkind to triple Afrezza production

    Dirk Perrefort | April 27, 2015

    Danbury based Mannkind expects to triple the manufacturing of Afrezza, an inhalable form of insulin approved last summer by the FDA. Photo: Contributed Photo / The News-Times Contributed
    Photo: Contributed Photo
    Danbury based Mannkind expects to triple the manufacturing of Afrezza, an inhalable form of insulin approved last summer by the FDA.
    Danbury based Mannkind expects to triple the manufacturing of Afrezza, an inhalable form of insulin approved last summer by the FDA.
    DANBURY -- Executives with Mannkind are tripling their production capacity at their local manufacturing facility in the hopes that demand for their drug Afrezza will continue to increase in the coming months.

    Afrezza, the first inhalable and fast-acting insulin, hit the market in February after several years in development by the drug company. The drug was first approved by the Food and Drug Administration late last year, and Mannkind (NYSE: MNKD) has since created a partnership with Sanofi to market the drug.

    Matt Pfeffer, chief financial officer for Mannkind, said the reaction about the drug from the marketplace has so far been positive. Many posting on social media about Afrezza are describing it as "a real game changer," while others say company CEO Alfred Mann is "an American hero."

    "Like any launch, it's going slow as expected but there are a lot of positive reports out there," Pfeffer said. "The difference people say the drug is making in their lives is very encouraging. Our hope is that as more people become aware of its benefits, word will continue to spread."

    Pfeffer said he's also pleased with progress being made at the Danbury plant, which is operating one manufacturing line that can produce up to 120 million cartridges of Afrezza annually. Pfeffer said during the current quarter, employees will expand the production to three manufacturing lines, which could mean a total annual availability of almost 360 million cartridges. The plant itself, on Casper Street, was designed for up to 12 production lines, Pfeffer said.

    On Monday, the company announced that the FDA approved a 12-unit cartridge strength that will hit the market soon. The company is offering 4-unit and 8-unit cartridges to provide a variety of dosing options.

    While company officials continue to be bullish about the future hopes of Afrezza, investors have been a little more wary until some hard data is available. While the stock hit a high of around $11 per share last summer when the initial FDA approval was announced, shares have since slid back to the low end of the stock's 52 week range. On Monday, the stock closed at around $4.59 -- a drop of more than 4 percent from the previous day's close.

  • Martin Shkreli
    @MartinShkreli

    $MNKD too HTB. stuck at 427,043 shares short. equity of co is intrinsically worthless. makes more business sense for them to stop production.

  • Invasive Insulin That Works!

    Amy Tenderich

    I can’t wait to get my next A1C test done (who says that?! but it’s true). I am now two-plus months into my use of new inhaled insulin Afrezza, and frankly I’m blown away by how well it performs (ooh, pun!)

    I’ve been hesitant to be too much of a cheerleader for Afrezza, because I thought maybe I was experiencing beginner’s luck – the thrill of any shiny new diabetes treatment can wear off pretty quickly – and given how controversial this drug is, I didn’t want to stir the pot unnecessarily.

    But sorry Naysayers, Afrezza is the bomb. At least for me.

    {I’d like to take a moment here to thank Sam Finta, aka @afrezzauser, for this insightful post warning investors off hounding us patients as we test the waters with this new drug – “Your financial good intentions to spread the message have blinded you to seeing there is a real person who will only trust and listen to a fellow warrior in the battle, and they (along with everyone they come into contact with) might reject or miss this “life-changing” drug based on your inappropriate behavior – can you blame them?”}

    I’ve written about the advantages of using Afrezza for all your bolus needs while on an insulin pump, and I continue to enjoy those.

    Today I’d like to share a little more detail about my own success with Afrezza. And we are hoping to share the experiences of other patients using it here at the ‘Mine soon, in a new series we’re calling “Afrezza in the Real World.”Afrezza in the Real World - DiabetesMine

    No, I’m not a marketing shill for MannKind or Sanofi; my use of this drug was strictly the choice of my doctor and I, and I’ve had no dealings with those drug makers other than interviews we’ve done with company execs in the course of reporting the news.

    I’ve simply become convinced that this first-ever operative non-invasive insulin has incredible potential to help everyone with diabetes.

    The Joys of Rapidity

    As I’ve noted, the rapid-on/rapid-off function of this insulin is a real game-changer, IMHO. I’ve heard people saying for years that our so-called “fast-acting” insulins are too slow, but I never realized how much that fact is the crux of struggling with the glucose roller-coaster until now.

    When you suddenly have something that peaks within an hour, and is out of your system almost immediately thereafter, you become keenly aware that most of the highs and lows of the past were caused by peak insulin action not matching up with peak glucose absorption, and by the insulin lingering in your bloodstream long after you needed it.

    In this 2009 interview I did with Al Mann, he explained that Afrezza essentially "turns off glucogenesis" so no glucose is secreted from the liver in reaction to food. For that reason, people with type 2 can use a set dose of Afrezza for meals and run essentially zero risk of lows no matter what the meal size, whereas type 1s “will still have the issue (of lows) if they dose and don't eat anything… and if they eat a large meal, they'll need a larger dose.”

    “The advantage for all patients is that they won't have to do carb counting or anything, because Afrezza does not have to be so precisely matched to food intake,” he adds.

    This, my friends, has proven 100% true for me, and it’s a HUGE life improvement to be relieved of all that math (and S.W.A.G. guessing).

    More Time in Range

    Simply put, Afrezza is helping me spend more time in range. My CGM screen now rarely shows the little dotted line going outside the borders of yellow for too-high and red for too-low. I’ve had whole days that remained in the white zone. And I’ve managed to do both a spin class and aerobics class starting at a “normal” blood sugar (100-ish) and ending there as well!

    For these morning workouts, I’ve learned that it’s best to take my regular Afrezza breakfast dose, and then just shut off my pump (basal insulin) for the hour-long workout or use a deeply reduced temp basal.

    I’m also using this tactic now to avoid going low when I need a small correction (from, say, 150-160 BG) and have no choice but to take 4 units of Afrezza.

    My BIGGEST WISH with Afrezza is that there were a 2-unit option – which would be perfect for type 1s like me in need of correction doses, I believe.

    On the flipside, I’ve found that when you are low(ish) after a meal or before a workout, you don’t need to panic as much as you did with subcutaneous insulin, when you just knew you were headed for a crash. Rather, I find it’s best to treat very mildly (tiny amount of sugar intake) and briefly (reduced temp basal for just half an hour) because that Afrezza will be out of your system in no time, allowing your BG to level off.

    For the first two weeks of April, you can see that 73% of my glucose readings were between 70-160, which is a big win for me:

    Glucose Data using Afrezza

    A Background Dilemma

    One question other users have asked me – and I’ve been trying to work out myself – is what to do when your glucose level remains ideal or even a little low after an Afrezza-covered meal but then starts to slowly rise thereafter. I find that when this happens, it usually it peaks at about 185, so still not the crazy 200+ spikes I often experienced in the past, but what to do here, when you’re pretty darn sure that another full 4 units will drop you too low?

    The only solution I’ve found so far is the one mentioned above: you go ahead and correct with the 4u of Afrezza, and then use a temp basal setting on your pump to dial back the full amount of insulin you’re getting in order to avoid a low.

    But if you’re not on an insulin pump? I have no idea how you would handle this.

    Some folks, including my own endo, have asked if it might be possible for folks like me to forgo using an insulin pump in the near future if Afrezza works so well. Based on what I just described, my answer is No. I still have the need to manipulate my background basal dose, to account for overcorrecting, exercise, and periods of higher insulin resistance, like PMS.

    Frog in My Throat

    One endocrinologist acquaintance of mine has been making skeptical faces at me whenever I say how much I like Afrezza; he’s still very concerned about the long-term effects on the lungs. And of course only time will tell how much this is an issue!

    Back in 2009, Al Mann told us they’d been following some patients who’d already been using Afrezza for up to 5 years, and saw no change in their lungs. (They did high-definition CT scans on the 600 patients in their study.) That seems encouraging.

    But I didn’t tell my endo friend that I’ve been experiencing a frog in the back of my throat and a bit of a cough. Since my nose has also been runny lately, I honestly can’t tell if it’s related to the Afrezza, and I hope with a passion it isn’t.

    If anything else is giving me pause about this drug, it’s simply the concern that uptake seems to be slow among doctors. That’s what I’m hearing, anyway – about endos who are ‘meh’ about offering it to their patients. Which makes no sense to me.

    Here we have the first-ever viable non-invasive insulin, that couldn’t be easier to teach or use, and that’s producing amazing results among early adopters. I know there’s some trepidation based on the past failure of Exubera, but Afrezza really is a whole new ballgame.

  • A Case Study for MannKind Shareholders, Re the United States Securities and Exchange Commission “SEC” approval of a Confidentiality Treatment Order “CTO” on December 15, 2014.

    MannKind Corporation (NASDAQ:MNKD) today discloses that the SEC granted the Valencia-based firm a Confidentiality Treatment Order.

    mnkd_banner.pngSource: MannKind

    “Based on representations by MannKind that this information qualifies as confidential commercial or financial information under the Freedom of Information Act, 5 U.S.C. 552(b)(4), the Division of Corporation Finance has determined not to publicly disclose it,” notes Brent J. Shields, Secretary of the SEC.

    As a ramification, MannKind can now legally withhold items 10.1 to 10.3 of fiscal 2014 third quarter report—details (like milestone payments) pertain to its commercial partnership with Sanofi (NYSE:SNY) as well as other Technosphere developments—from the public.

    The mentioned CTO is valid for up to three years, from the date of MannKind’s latest quarterly filing on November 10, 2014 to the same date in 2017.

    As one of nine exemptions under the U.S. Freedom of Information Act “FOIA” and in accordance to the SEC Rule 24b2, a CTO protects corporations from having to disclose their “trade secrets and commercial or financial information” considered as “privileged or confidential.”

    Sometimes, keeping a closed-lid on the developments and launch strategies of a revolutionary pipeline of medicines and biotechnologies is prudent: That can strengthens the firm’s moat, thus, ensuring future profits for shareholders.

    Nevertheless, there are also potential negative ramifications to the CTO.

    In an excellent Investopedia article written by author Eric Fox, the author stated, despite the SEC does not grant all CTO, the Commission is still “allowing too many secrets on Wall Street.”

    “An overly broad and inconsistent application of the confidential treatment order procedure does not benefit investors,” Fox noted and continued, “I feel the government should err on the side of more disclosure as a general rule.”

    While we do not debate the merits of the CTO executed by MannKind and Sanofi; it is undeniable that shareholders benefit from being better informed on the commercial partnerships as well as Technosphere’s ongoing developments.

    For instance, MannKind to disclose information that involves Technosphere reformulation of pain medicines would be instrumental, in instilling more confidence in the company.

    Further, if MannKind to confirm Sanofi’s timeline for the marketing and launch of Afrezza, investors’ faith in both Dr. Alfred Mann, CEO and Founder, and the management will be galvanized.

    Regardless of MannKind corporate strategy, investors who want to stay abreast of Technosphere developments can still do so, by keeping tabs on its filing with the U.S. Patent Trade Office. The intelligent shareholders can also conduct informal surveys with their healthcare providers to gauge at the progress of Afrezza’s upcoming launch, scheduled for the first quarter of 2015.

  • New REMS label approved 4/20/15
    AccessdataDOTfdaDOTgov/drugsatfda_docs/appletter/2015/022472Orig1s002ltr.pdf

  • MNKD Calls vs. Puts

    By paying attention to the amounts of calls vs. the amount of puts, we can get a gauge of where investors think the value of a stock is going to go. According to Schaeffer’s investment research, MNKD stock currently has a 16.91 call/put ratio. That means that for ever put purchased, investors are purchasing nearly 17 calls on the stock; insinuating that overall, investors are expecting growth.

    Could This Be Short Sellers Hedging Against Losses?

    If the ratio was a bit smaller, I would say that a hedge is a possible reason for the increase in calls. However, the number of calls vs. puts is exceptionally high. While I’m sure that short sellers are hedging and that is lending a hand to the growth in the ratio, there’s also another reason for the calls. Investors are looking for growth!

    The reality is that when we look at physician feedback, MannKind’s Afrezza is a great alternative to other insulin products. It reduces critical spikes and declines in blood sugar, and gives patients peace of mind. While I would agree with the nay sayers that say Sanofi (NYSE: SNY) isn’t doing a good job of promoting and selling the insulin, we can’t discount that with a great product like this word-of-mouth will lead to growth in sales of the insulin.
    cnafinanceDOTcom/mannkind-mnkd-stock-calls-far-out-number-puts/2784

  • faqsDOTorg/patents/app/20150080298

  • Pilot study with technosphere/PTH(1-34)--a new approach for effective pulmonary delivery of parathyroid hormone (1-34) to increase bone mineral density in patients with osteopenic disorders. That's a BIG market!

    ncbi.nlm.nihDOTgov/pubmed/12916003
    mannkindcorpDOTcom/collateral/documents/english-us/101lr-technospheretechteaser-01.19.11.pdf

    This is the best part:

    "No differences were seen between pulmonary and subcutaneous application with regard to the PTH(1 - 84), calcitonin and calcium concentrations. In conclusion, pulmonary application of Technosphere/PTH(1 - 34) appears to be an effective and thus attractive candidate for PTH substitution therapy in osteoporosis and other conditions leading to a decrease in bone mineral density."

    Eli Lilly has Forteo (an expensive, daily injectable (e-coli derived) recombinant PTH for bone density and pagetts disease. It works to increase bone formation instead of halting resorption as all the bisphosphonates like Fosomax, Actonel, Boniva, etc. do. Unigene (Bkpt- IP and assets now in a new company beginning with 'E' can't remember) had a PII next gen enteric coated oral PTH that looked good, but partner GSK backed out, variable bioavailability was always suspected but not clear that was an issue any more.

    This market is the osteoporosis, osteo-athritis space. BIG.

    Abstract

    Sequential subcutaneous PTH injection therapy (repeated 14 days of PTH administration and a subsequent treatment pause for a few weeks) is known to increase bone mineral density in patients with osteopenic disorders. Alternative methods of drug delivery may be beneficial in increasing compliance. A pilot study was performed in 10 healthy volunteers (4 female/6-male, age: 25.6 +/- 3.5 years, BMI: 22.3 +/- 2.4 kg/m 2, mean +/- SD) to assess the pharmacokinetic profiles of 1600 IU of PTH(1 - 34) using the pulmonary Technosphere drug delivery system in comparison to a subcutaneous injection of 400 IU. The treatments were administered in the

  • FEATURED SPEAKER
    2:55 Dry Powder Formulations for the Inhalation of Oxyntomodulin
    Andrea Leone-Bay
    Vice President Scientific Research
    MannKind
    Obesity is a rapidly becoming a global epidemic and underlies many disease conditions including diabetes and cardiovascular disease. Current treatment options are limited and are challenged by undesirable side effects. Oxyntomodulin (OXY) is an endogenous peptide hormone that signals satiety in healthy individuals. High circulating OXY concentrations are associated with satiety and low OXY concentrations are associated with a feeling of hunger. This activity profile positions OXY as a potential treatment for obesity. To address this unmet medical need, this presentation will introduce an approach to developing an orally inhaled dry powder OXY product administered using a small, breath-powered inhaler for obesity therapy.

    The audience will learn about oxyntomodulin, a potential new obesity therapy and about the administration of peptides by oral inhalation using a simple, patient-friendly approach.

  • Hakan promised to deliver a signed TS deal by Feb 2015 end. He rarely didn't deliver. Sny is interested in inhaled GLO-1, pain mgmt, oncology.

  • One Giant Leap for MannKind [& Sanofi]

    MOULDING_JEZ_1

    In October, I arrived in the U.S. from my former post as head of Sanofi’s Japan/Pacific region, which includes Japan, Australia, New Zealand and South Korea. Since that time, I’ve spent a lot of time listening and asking questions, and in the process, I’m beginning to learn more about our teams in America and Canada.

    What I’ve learned in that time is that we have a dynamic, talented team in Sanofi US. We have the potential to launch seven new products in the U.S. by 2017. With this opportunity to reach millions of patients with our medicines, I find myself more energized now than at other point in my career.

    Earlier this month, our team celebrated an especially significant milestone, launching the first of those seven new products. Afrezza® (insulin human) Inhalation Powder, the only inhaled insulin, is now available by prescription in the U.S. Click here for Full Prescribing Information for Afrezza® including Boxed WARNING.

    To me, the launch of Afrezza embodies the type of innovation we strive for – not only bringing a new treatment option to market, but doing so with a treatment that can address challenges people living with diabetes face.

    When we announced our global licensing agreement with MannKind Corporation last summer, we knew there was a great deal to be done in a short period of time. This launch would not have been possible without the hard work of our dedicated colleagues and the collaboration of our counterparts at MannKind.

    We’re ready for a promising year ahead, and this is an exciting start.

    INDICATION

    Prescription Afrezza is a rapid-acting inhaled insulin used to treat adults with type 1 and type 2 diabetes for the control of high blood sugar.

  • Matthew, type 2 from Oregon, asks: I’m confused about the new basal insulin Toujeo, I understand that it is U-300 and therefore should be more “concentrated,” but when I went to the webpage for this product, it talked about how Toujeo is a 1:1 dosing and conversion from Lantus. I thought that the dose would actually be less as it’s more concentrated. I also read about how people actually required a higher dose of Toujeo to allow the same blood sugar control as with Lantus. How on earth does this all work?!

    Wil@Ask D’Mine answers: It’s fuzzy math, Mathew, but you chose the right person to ask. However, a warning: It’s impossible to give a concentrated answer about concentrated insulin! So OK, let’s concentrate (get it?!)…

    Most modern insulins are what we call U-100, which means that there are 100 units of insulin per milliliter of fluid. That’s what they mean by its concentration. Back in the day we also had U-20, U-40, and U-80 insulins. I also had it in my head that there was a U-60 at one time, but I may be wrong about that, as a quick Google search only turns up articles about the German Sub U-60, which apparently had one of the least distinctive war records of the Nazi fleet -- and no discussions of insulin.

    Anyway, back in the many-concentration days, each insulin had its own syringe. If you got the wrong syringe or the wrong vial from the pharmacy… Well, I’ll leave that to your imagination, but one survey in 1967 found that fully half of diabetes patients on insulin were making dosing errors due to the overlapping and confusing systems. That ultimately led to the adoption of the single U-100, initially here in the U.S. and Canada and eventually worldwide. See? Once-upon-a-time we Americans were on the leading edge of diabetes care instead of on the trailing edge we often find ourselves on today!

    Today, nearly all insulins—be they basal, “N,” fast, rapid, or mix—are U-100.

    Except, of course, U-500, the super-concentrated, five-times-more-powerful insulin we have for those who need more than 250 units a day of the conventional stuff. U-500 gives pharmacists fits because they are purists and believe that U-500 should be administered only in tenths and twentieths of an mL in a Tuberculin syringe. While they are technically correct, there’s nothing wrong with the in-the-trenches workaround of just using U-100 syringes and taking 1/5 the dose you would have taken of U-100. Units are technically pure, but patients don’t care.

    And now, apparently, Toujeo maker Sanofi doesn’t care either, because they just tore up the Unit Rulebook and threw it away. The reason that Toujeo doses 1:1 (meaning you’d take the same number of “units” that you did before) is that Sanofi has re-defined the unit. Toujeo comes only in a special SoloStar pen that actually delivers 1/3 of a unit with each click. In fact, the 450 “unit” pen actually only holds 1.5 mL of fluid, exactly half the volume of the pens we are used to. Basically, the new pen has been recalibrated to deliver smaller doses. For each single “unit” you click into the pen, you’re actually getting one-third of what you are accustomed to but of a higher potency liquid.

    It’s hard to wrap my brain around all the numbers, but I think, in general, this is safer. We have to get away from thinking of a unit as something pure and recognize that it’s nothing more than a reference number, rather than an actual dose.

    Now, what about that whole needing more thing? Well, even though Toujeo is nothing more than maToujeople syrup-thick Lantus that’s three times more concentrated, for some reason it doesn’t work three times better. If you were well controlled on, say 100 units of Lantus, taking 100 of the new one-third 100 units of Toujeo won’t control you.

    How much more would you need?

    Well, I crunched the numbers for you, Matt. Let’s say you needed 100 units of Lantus. If you switched to 100 “units” of the new stuff you’d be getting the volume equivalent of 33.34 units because it’s three times more concentrated. Of course, with this stuff not being as strong as Lantus you’d then need to increase that number, worst case for you as a type 2, by 15%. Looking at it through a U-100 lens, that means you’d need to take a hair over 38 units, a volume reduction of 62 units, or about a 60% reduction in volume. OK, it’s not the 2/3 reduction you’d expect in a U-300 insulin, but it’s not chump change, either.

    Of course, if your pen conked out, you’d need to keep your wits about you if you used a U-100 insulin syringe to suck out an emergency dose. Remember the “units” on the Toujeo pen are smoke and mirrors. If you don’t remember that, you’ll give yourself a triple overdose (minus 11-17%).

    Some oddball things you need to know: Toujeo is so extended that onset of action is not for six hours, and it can take “at least five days” for the insulin-lowering action to “manifest.” Because of this, doctors are advised not to use the typical daily up-titration to adjust the dosage, but to increase every 3-4 days. A pen is good for 28 days, and can be kept at room temp (if your room is cooler than 86 degrees) during that time. And I’ve read that Sanofi is pricing the new juice at about the same dollar-per-unit as Lantus, but I’m not clear which math they are using: The one that uses less juice for the buck or the one that would be three times higher.

    Now, there was much excitement earlier about the fact that Toujeo was supposed to be less hypo-prone, but the labeling doesn’t support that, and that has investors upset. And speaking of investors, why a U-300 at all? It could be because Americans—type 2s and type 1s alike—are getting fatter and fatter. The more you weigh, the more insulin you need. Many PWDs need so much insulin nowadays that the tissues can’t absorb it correctly. The solution is more concentrated insulin. OK, you say, but if we already have U-500, why add another one?

    Because, frankly, U-500 ain’t that great. It has a camel-shaped action curve sort of like the old NPH. This means that six to eight hours downstream of a shot, it reaches peak action, giving rise to the risk of lows at odd hours. It’s also only a 12-hour insulin. So there’s certainly a market for a more concentrated 24-hour basal.

    Or, people more cynical than I might suspect that Sanofi is freaking out because their cash cow just got sent to the slaughterhouse. Lantus is out of patent and Eli Lilly and company are poised to release generic Lantus to compete, a move delayed only by a strategic lawsuit filed by Sanofi.

    Only time will tell if Toujeo is a game-changer like Lantus was when it was first introduced, or if it turns out just to be Lantus repacked in a shiny new patent.

SNPS
46.82+0.20(+0.43%)4:00 PMEDT