|
Post by compound26 on Jun 3, 2015 16:54:10 GMT -5
There is thread regrading this in Tudiabetes.org. Below is the link to the discussion: www.tudiabetes.org/forum/t/afrezza-los-angeles-times-article-3rd-june-2015/46495Below are some of the comments posted there: johnhindepost LA Times June 3rd, 2015 : MannKind's inhaled insulin drug proves hard for diabetics to get www.latimes.com/business/la-fi-mannkind-drug-20150603-story.html#page=122 … DrBB Interesting. Mostly a business article but better than most about focusing on aspects besides the fact that it eliminates injections ("ew, injections!"), which it doesn't anyway and is actually to me the least significant thing about it. I almost wish "inhaled insulin!!!" wasn't part of it, since it's the different way the stuff behaves that's its real significance, not the fact that it can be administered without icky needles. karen57 ^^^ ditto what DrBB said! Also in the article, this quote: "The nice thing about Afrezza is it works instantly for me," said Goldstein, 66, who has had Type 1 diabetes for more than 15 years. "I take my puff after I've been eating awhile, and my blood sugar never goes really high." may be true but if Goldstein has her basal set properly then this would be true for 'mealtime' injected bolus insulin as well. At least there was some information about the cost, I've been looking for some comparison so yay. Jenny The cost is probably higher than reported, if the experience of the high profile people tweeting is anything to go by. Eric Fenar, who is among the most vocal, was reported as saying at the MannKind shareholders meeting that he is using 4 boxes a month. That is about a thousand bucks' worth of insulin, and if you think insurers are going to pay for that, when there is no peer reviewed data pointing to better outcomes than using a pack of pens, I have a bridge to sell you convenient to NYC. The problem comes in that they only give you 90 doses per box, so even if the size dose is right you can only cover 3 meals a day. No snacks. No corrections. And since the insulin is so short acting, you are likely to need corrections at 2 or 3 hours to cover the rest of the glucose from your meal. For early Type 2s who really just need that first phase insulin replaced, the stuff looks like it could be really good, but the problem is doctors aren't going to be putting Type 2s on any insulin early, since they have been brainwashed that they should put them on the GLP-1 drugs first in the erroneous belief these will grow back healthy beta cells. So they are only putting older, very late Type 2s on insulin who have lost their insulin producing capacity and would be needing those correction doses too. But since doctors are told to prescribe one dose per meal, they won't be suggesting these patients use corrections. So they will get crappy numbers, and insurers will get confirmation that there is not advantage to Afrezza. Why is it that so few doctors seem to understand what first and second phase insulin are all about? The info is out there. We are paying them a lot of money to supposedly know more than we do about diabetes. But they don't.
|
|
|
Post by compound26 on Jun 3, 2015 16:13:08 GMT -5
Below are some of the comments to this report on LA Times' website. I am glad that LA Times is giving publicity to Afrezza in a balanced/neutral report. Rank 4553Quite sad that after a company invests in R&D and FDA approval, real innovations in medicine that can help people then are bogged down in the "healthcare system." This is a great story for all those who think single-payer healthcare solutions will kill innovation. clu97531I have been a Type 1 diabetic since the age of 12. I'm 50 now! I followed the progress of Afrezza through the years, which means I also followed the glowing reports from those who participated in the trials which, eventually, enabled Afrezza to become approved by the FDA. I wanted to try it because of all the subcutaneous scarring in the injection areas and for ease of use/delivery. 50,000+ injections through the years cause the scarring as one can only inject in so many places. The areas become hard and dimpled and are noticeable without clothing. This fact aside, the way Afrezza works compared to Humalog is WAY more than expected. The inhaled insulin is spectacular! It takes a week or so of "figuring it out" but if a diabetic has a Continuous Glucose Monitor (CGM) to see the real-time results on the blood sugar level,....Afrezza really is a no brainer. Afrezza is not a "magic pixie dust", you must still eat right and exercise. This is a good thing! Bottom line, Afrezza works far better than I expected! I feel much better overall !! My blood sugar does not experience the roller coaster rides and hypoglycemic episodes (low blood-sugar) like it does on Humalog. If you are a diabetic, you really should seek out Afrezza. Again, no brainer! As for fears of the unknown on the lungs, I'd rather improve my quality in a HUGE way, than fear an unknown that in all likelyhood will show no future issues.... DrBBennett"It allows them to control their glucose ... in a manner that doesn't stigmatize. If you're out at a restaurant, the last thing you want to do is go to the bathroom for an injection or stick a needle through your clothing." Meh. I never felt any stigma about injecting in a restaurant--I don't think anyone has ever even noticed. Nor is giving yourself an injection that big a deal. If you have to, you have to. First few times maybe but if it's that or die, well, you get used to it pretty fast believe me. What bugs me about the coverage of Afrezza--though this article is much better than most--is that all the emphasis is on the "eww, injections!" problem, when in fact the "breakthrough" is not how you take it but how the molecule behaves: it's faster taking effect, it clears out of your system sooner, and there's MUCH less of a problem with hypoglycemia--low blood sugar, aka "insulin reaction." THAT's the problem that causes the most day-in day-out fear and anxiety. If you've never experienced it, you have no idea. And no, feeling a little weak or trembly when you haven't eaten, the way some people do, is nothing by comparison with having something in your system that is literally SHOVING your blood sugar down, you're getting tunnel vision, hard to speak, knees locking up and almost unbearably ravenous hunger. As a Type 1 diabetic for over 30 years, THAT'S the aspect of Afrezza that interests me. The injection business? big whoop. Particularly since it does NOT eliminate injections. For a T1 like me, you still have to have a basal insulin running 24/7, either via a pump (and yes those patches involve piercing the skin) or a long-acting insulin like Levemir or Lantus. Afrezza MiracleIt's grossly ignorant for those doctors and commenters to say Afrezza is equal to injection mealtime insulin. In fact, Afrezza is the only insulin on the market that can mimic human's first phase and second phase insulin. Why? Because Afrezza is monomer, all the other injection insulins are hexamers. How important is the first phase of insulin? It's well established that loss of first-phase secretion and reduced second-phase secretion are characteristic features of type 2 diabetes mellitus (T2DM). It is also well known that a decrease in the first phase of glucose-stimulated insulin secretion is found in the early stage of T2DM and also in impaired glucose tolerance (IGT). This is the reason that Afrezza could be the most cheapest and effective way to slow or reverse diabetes early in medical treatment. Yes, potentially reverse T2 diabetes at early stage! For more details, please read the fantastic article by Distinguished Professor Emeritus in Diabetes Care/Pharmacotherapy, Washington State University College of Pharmacy. Afrezza: Treating Diabetes in a Physiologic Manner www.diabetesincontrol.com/articles/features/16635-afrezza-treating-diabetes-in-a-physiologic-manner Because of Afrezza's mimicry of first phase and second phase insulin, the users in Afrezzauser's group miraculously achieved drastic reduction of HbA1C. Please go through every blog of Afrzzuser, especially you are a diabetic. afrezzauser.com/blog/ Afrezza is a miracle drug, priced at comparable price of injection mealtime insulins. jonxnelson
when you are diabetic and eating out with others, you won't have to excuse yourself so that you can inject your insulin in a bathroom. Instead, you can put the "whistle" to your mouth and inhale your insulin. I see this drug as a great boon to all diabetics who can use it. hillsaveI don't know why some people think the process of getting Afrezza is so difficult. I went to my GP because for 2 yrs he's been telling me my fasting Blood Glucose levels were running high. Avg about 140 fasting. He gave me a script for a meter and strips and a pricker. For two weeks I wrote down everything I ate and recorded my BG before and after I ate every meal. Was I surprised. It was going to 269 after meals. Need to keep that down to a max of 140 all the time. Went back to him, showed him my meter and book. I passed the Spirometry test in his office and asked him for Afrezza and "told" him to give me 4U (90 in a box) which I told him I would start with just 4 U at dinner time. One month later I went back to him, showed him my meter and his reply was WOW. Wrote me a new script for combo of 60(8U) and 30(4U) with 5 refills. Well I can't tell you how happy I am. Afrezza goes to work in 10 minutes. NO LOWS. I can eat a fair amount of carbs (110-last night was 200 at a restaurant) and took 8u at the table during appetizers and another 4U when my wife ordered a huge piece of Browny with 3 scoops of Ice Cream/whip cream on top. Our son helped too. Two hours later I was 108. 4 hours later I was 162 so I inhaled (took 1 sec)another 4U. Woke up at 6AM I was 125. Everyone I here from who is using Afrezza, which includes my 26 yr old T1 son, couldn't be happier that they do not have to use injectable insulin at meal times any longer. Even if you weren't as lucky as me and the total time it took to get on Afrezza was24 hours of your time you would gain a life time of positive changes in your handling of your Diabetes. SO don't walk, RUN to your doctor. Exercise would be good for you. Thanks for reading my comment.
|
|
|
Post by compound26 on May 27, 2015 13:48:08 GMT -5
Could Afrezza have helped him control his Type 2 diabetes? Coroner, Doctor: B.B. King Died After Series of Mini Strokes www.yahoo.com/music/coroner-doctor-b-b-king-died-after-series-of-119060720526.html?soc_src=mail&soc_trk=maAssociated Press May 15, 2015 Tim Mosenfelder/Getty Images LAS VEGAS (AP) — B.B. King’s physician and the coroner in Las Vegas say the 89-year-old blues legend died of a series of small strokes attributable to his longstanding battle with type 2 diabetes. Dr. Darin Brimhall and Clark County Coroner John Fudenberg (FYOU’-den-berg) tell The Associated Press the medical term for the cause of death is multi-infarct dementia. It’s sometimes referred to as MID, and is also called vascular dementia. Dementia is a permanent loss of brain function that occurs with certain diseases, including diabetes. It usually affects adults over age 55, and can affect memory, thinking, language and judgment. Brimhall says King’s strokes resulted from reduced blood flow as a consequence of chronic diabetes — or unhealthy fluctuations in blood sugar levels. King was diagnosed with type 2 diabetes many years ago.
|
|
|
Post by compound26 on May 27, 2015 10:46:31 GMT -5
LOL about the last paragraph. "In addition to reporting the current status of the development of inhaled insulin, our report illustrates a simple but important truth: making an innovative product take root can only be regarded as an initial success, to make it flourish and bear fruit, intensive care is needed. MannKind is doing so."
|
|
|
Post by compound26 on May 26, 2015 23:34:13 GMT -5
Let's look at the adoption history of RAAs and basal (Lantus). Even Levemir (a distant second to Lantus and approved 5 years after Lantus) managed to pull in about $1.4 billion (based on Latus' sales number referenced below and dividing it by four) on the 6th year of its launch. Not bad at all. If one views Afrezza as the first drug in its category ( Ultra Rapid Action Insulin), it is not unreasonable to expect Afrezza to reproduce the growth path of Lantus in terms of sales. Humulin, as the commercial product was called, revolutionized diabetes treatment when it became widely available in the early 1980s. Today, almost all diabetic people use recombinant human insulin instead of animal insulin. In 1996 the Food and Drug Administration approved a modified human insulin called Humalog, which was specially developed to be active very quickly after injection. www.med.uni-giessen.de/itr/history/inshist.htmlApproved in 2000, insulin glargine ( Lantus) was the first basal insulin analog to become available in the United States. Insulin detemir(Levemir) was subsequently approved in 2005. www.jfponline.com/index.php?id=22143&tx_ttnews[tt_news]=165850Although some smaller companies sell insulin only in emerging markets such as China and India, three companies dominate the global insulin market in terms of revenue: Novo Nordisk (41%), Sanofi (32%), and Eli Lilly (20%). All three participate in the rapid-acting analog market. In 2011, Novo Nordisk, Sanofi, and Eli Lilly achieved rapid-acting analog sales of $3.9 billion, ~$270 million, and $2.4 billion, respectively. Sanofi dominates the basal analog market; 2011 sales of glargine (Lantus) totaled $5.5 billion, nearly four times that of its main competitor, Novo Nordisk's detemir (Levemir). Eli Lilly does not currently market a basal analog, although it has two in development. Novo Nordisk and Eli Lilly are the largest distributors of human insulin (both regular and NPH), with sales of $2.0 billion and $1.3 billion, respectively. clinical.diabetesjournals.org/content/30/4/138.fullInterestingly, based on timeline outlined above, it appears Humalog was approved about 14-16 years after Huminlin was widely used. Afrezza was also approved about 14-16 years (2014) [give or take one or two years, if one wants to] after Humalog was widely used (based on the link below, it appears Humalog sales was $350 million in 2000 and $628 million in 2001; Humalog sales caught Huminlin sales in 2003 ( after 7 years of Humalog's approval). In that year, they each had a sales of around $1 billion). Interestingly, in 2008 (that is 12 years after Humalog was approved), Huminlin still had a sales of around $1 billion, while Humalog had a sales of around $1.7 billion. After 7 years of its approval, Humalog passed Huminlin in terms of sales. So will Afrezza sales pass the combined sales of all RAAs by the seventh year of its approval (2021)? en.wikipedia.org/wiki/Annual_pharmaceutical_drug_sales
|
|
|
Post by compound26 on May 26, 2015 16:59:00 GMT -5
Let's look at the adoption history of RAAs and basal (Lantus). Even Levemir (a distant second to Lantus and approved 5 years after Lantus) managed to pull in about $1.4 billion (based on Latus' sales number referenced below and dividing it by four) on the 6th year of its launch. Not bad at all. If one views Afrezza as the first drug in its category ( Ultra Rapid Action Insulin), it is not unreasonable to expect Afrezza to reproduce the growth path of Lantus in terms of sales. Humulin, as the commercial product was called, revolutionized diabetes treatment when it became widely available in the early 1980s. Today, almost all diabetic people use recombinant human insulin instead of animal insulin. In 1996 the Food and Drug Administration approved a modified human insulin called Humalog, which was specially developed to be active very quickly after injection. www.med.uni-giessen.de/itr/history/inshist.htmlApproved in 2000, insulin glargine ( Lantus) was the first basal insulin analog to become available in the United States. Insulin detemir(Levemir) was subsequently approved in 2005. www.jfponline.com/index.php?id=22143&tx_ttnews[tt_news]=165850Although some smaller companies sell insulin only in emerging markets such as China and India, three companies dominate the global insulin market in terms of revenue: Novo Nordisk (41%), Sanofi (32%), and Eli Lilly (20%). All three participate in the rapid-acting analog market. In 2011, Novo Nordisk, Sanofi, and Eli Lilly achieved rapid-acting analog sales of $3.9 billion, ~$270 million, and $2.4 billion, respectively. Sanofi dominates the basal analog market; 2011 sales of glargine (Lantus) totaled $5.5 billion, nearly four times that of its main competitor, Novo Nordisk's detemir (Levemir). Eli Lilly does not currently market a basal analog, although it has two in development. Novo Nordisk and Eli Lilly are the largest distributors of human insulin (both regular and NPH), with sales of $2.0 billion and $1.3 billion, respectively. clinical.diabetesjournals.org/content/30/4/138.full
|
|
|
Post by compound26 on May 26, 2015 15:41:02 GMT -5
The bullet points suck. They are all bearish. Sold out. $4.80 all shares. Thanks for the update, fugacity. But I do not think these points are bearish or they change anything we currently see. Sure it is not easy to change the label. But this is true for Toujeo and to that matter any future competitor of Afrezza as well. Sure US patients seem to be slow to embrace new treatments, but Insulin pens vs vial-syringe-needle systems probably isn't such a leap forward either. And I do view the last point (that Sanofi appears to be in the process of conducting study on real-life Afrezza use to see if patient enthusiasm translates into patient compliance) as a positive sign.
|
|
|
Post by compound26 on May 26, 2015 15:15:19 GMT -5
K I'm selling. Thanks for making up my mind. fugacit, what are you talking about?
|
|
|
Post by compound26 on May 26, 2015 14:05:06 GMT -5
Here is the article for your easier reference. It appears to be a good article worth reading. Assuming what was stated in the article to be true, here are a few of my observations from reading the article: 1. It is not easy to get an improved label (like less hypo) from FDA. Toujeo did not get a better label even though studies indicate a 31% less hypo. Therefore, it probably isn't likely that we will see an improved label for Afrezza in the near future. 2. It probably is easier to get a better label in EU. Based on the article, Toujeo did get a better label in EU. The same may be true for Afrezza. 3. US patient seem to be less interested in trying-out new treatments. (Based on the example of insulin pen adoption. “These advantages have attracted significant user numbers in almost every wealthy country around the world except for the United States, where their adoption among insulin users may still be under 10%.”) In that sense, it is appears the US market is the most difficult market for Afrezza to break in. 4. Item 3 above suggests that patients in other markets, EU and Japan, for example, are generally much more interested in trying-out new treatments. In that sense, it is appears the EU and Japan market may be an easier market for Afrezza to break in. This, in combination with item 2, seem to suggest that the EU and Japan market is really worth exploring as early as possible. 5. Sanofi seems to be pricing Afrezza more expensive than RAAs (“$7.54 per day compared with $3.14 for Apidra”). Not sure if this is true (and I believe there has been some discussion on this board regarding this). But this may be an issue that needs Mannkind and Sanofi to look into, especially considering the fact that some earlier adopters reporting using a few boxes of Afrezza per month (and getting excellent results . 6. Sanofi appers to be in the process of conducting study on real-life Afrezza use to see if patient enthusiasm translates into patient compli-ance. (“Berria says the company will study real-life Afrezza use to see if patient enthusiasm translates into patient compli-ance, and that it will follow real-world Toujeo users to measure the practical effect of its longer, steadier flow of medication.” “Sanofi and MannKind are planning post launch research...”). If this is true, this is yet another piece of evidence that Sanofi is seriously working on marketing Afrezza (which is in direct contradiction of shorts' argument and assumption that Sanofi is not really working on marketing Afrezza). Toujeo and Afrezza: New and Improved Insulins, Limited by FDA Labeling Constraints www.ajmc.com/journals/evidence-based-diabetes-management/2015/may-2015/Toujeo-and-Afrezza-New-and-Improved-Insulins-Limited-by--FDA-Labeling-Constraints#sthash.1cxyj7Yj.dpufTwo new insulins marketed by Sanofi offer improved options for patients: Toujeo is longer acting than its predecessor, Lantus. Afrezza, an inhaled insulin, is gaining praise from patients, if not from Wall Street. Published Online: May 19, 2015 Andrew Smith Existing treatments are effective enough to control diabetes in most patients, but drug makers spend huge sums to keep developing new products and improving old ones. Indeed, Sanofi just rolled out 2 novel versions of the very oldest diabetes treatment, an insulin glargine formulation called Toujeo and an inhalable form of human insulin called Afrezza. Sanofi officials say both products will benefit large numbers of insulin users with both type 1 and type 2 diabetes mel-litus (T1DM, T2DM). Outsiders express a wide range of opinions. Trial data indicate that Toujeo controls glycated hemoglobin (A1C) levels about as well as Lantus, an insulin glargine formulation approved in the year 2000 that has just lost patent protection after years of blockbuster sales. Toujeo lasts longer than Lantus, however. It also provides the body a steadier stream of insulin1 and is associated with a significantly lower risk of nocturnal hypoglycemia. Afrezza performed similarly in a phase 3 trial. It roughly matched an existing competitor, insulin aspart (Novolog), in A1C reduction, and slightly outperformed it in several secondary ways. Afrezza use was associated with less hypoglycemia, lower fasting blood glucose, and slight weight loss rather than slight weight gain. It also reached peak levels very quickly, in just 12 to 14 minutes on average. That said, Afrezza’s medical importance will likely hinge on something that no trial can measure: how the change from injection to inhalation affects patient behavior. If the delivery method inspires patients to medicate themselves more consistently, Afrezza could produce huge health benefits. If patients use Afrezza like they use insulin aspart (a fast-acting insulin analogue), the new product could prove to be an expensive convenience. Financial analysts mostly predict solid but unspectacular sales for both drugs , in part because federal regulations for-bid Sanofi from touting the comparative advantages of either drug. ( The FDA did not allow language about less hypoglycemia in the label it approved, and therefore Sanofi cannot mention it in language it uses to promote the drug.) Consensus estimates reported by Bloomberg predict annual Toujeo sales will reach about $1.3 billion by 2020 far below the $7.1 billion that Lantus generated in 2014. As for Afrezza, annual projections range from a paltry $182 million up to $2 billion, with the median in the $600 million range. The treatment’s unexpectedly poor performance during its first month on the market led Goldman Sachs to cut its annual sales projections by $1 billion. In other respects, however, both medications have gotten a good reception. “ The response to Afrezza on social media has been tremendous,” Rachele Berria, MD, PhD, who heads the Diabetes Medical Unit for Sanofi US, told Evidence-Based Diabetes Management in an interview. “Healthcare providers don’t seem to anticipate that patients will see much of a need to move away from injections, but actual patients see this as a valuable feature.” Berria says the company will study real-life Afrezza use to see if patient enthusiasm translates into patient compli-ance, and that it will follow real-world Toujeo users to measure the practical effect of its longer, steadier flow of medication. “The goal in treating diabetes is to avoid peaks and valleys in both insulin and sugar, and Toujeo does that to a degree that once seemed impossible,” she said. “There’s no insulin spike when each new injection gets absorbed, and there’s no loss of efficacy in the final few hours. It’s a big stride forward from Lantus.” Physicians have been using insulin to treat diabetes since 1922, when Frederick Banting and Charles Best injected the hormone into a diabetic teenager at a hospital in Toronto. Eli Lilly began producing it commercially within the year, and diabetes was transformed, virtually overnight, from a speedy death sen-tence to a chronic condition. Intermediate acting Neutral Prot-amine Hagedorn (NPH) insulin arrived about a quarter century later, in 1950. Long-acting insulin, on the other hand, didn’t reach patients until 2000, when Lantus went on sale in the United States and Europe. The new drug reduced A1C levels about as much as NPH insulin, but trials demonstrated that it produced a greater reduction in fasting plasma glucose and fasting blood glucose as well as a far lower risk of nocturnal hypoglycemia. The other big advantage of Lantus was the convenience of longer action. Patients who had spent years toting around basal insulin and setting alarms for midday injections suddenly had nothing to carry and nothing to remember except a single injection before bed. By then, of course, insulin was not the only effective treatment for T2DM. The FDA had approved metformin in 1994, and its huge success spurred drug companies to develop the other oral treatments that now crowd the market. Many of these treatments are quite effective, especially when used in combination. Indeed, if used properly, their excellent disease control could greatly reduce diabetic complications and the need for new drugs. Yet pharmaceutical companies continue developing treatments like Toujeo and Afrezza because a huge percentage of diabetics fail to control their condition with current options. A recent study that examined records from more than 43,000 patients found that less than 55% of all Americans who have been diagnosed with diabetes, and prescribed medication to control blood sugar, actually man-age to keep their A1C level under 7%. The main cause of this problem seems to be patient behavior. Studies have found that patient adherence to oral treatment protocols can range from more than 90% down to just over 50%. Strict adherence to guidelines concerning injectable medications and proper diet tends to be lower, while strict ad-herence to guidelines concerning mod-erate, regular exercise and blood sugar checks is downright rare. The chance that any patient will adhere perfectly to a complex regimen is low, and studies of people with all types of chronic disease have typically found that only about half of them will make a serious effort to manage their condition. The consequences of this behavior are dire. Diabetes is the nation’s seventh-lead-ing cause of death. It increases the risk of stroke (by 50%), heart attack (by 80%), and death from cardiovascular disease (by 70%). It is also the leading cause of kidney failure and non-traumatic lower limb amputation. The American Diabetes Association estimates that the di-rect medical cost of treating diabetes reached $176 billion in 2012, and indi-rect costs such as lost productivity add-ed another $69 billion to the tally. Studies have demonstrated that in-creased adherence to a treatment regi-men can reduce A1C levels, and many other studies have shown that A1C reductions prevent complications. A 1% reduction in A1C is associated with a 14% reduction in the risk of heart attack and a 40% reduction in the risk of eye, kidney, and nerve disease. (Logic says that better adherence would also slash healthcare costs, but the findings from research on that topic are mixed.) A number of experiments have tested different strategies for improving ad-herence to existing treatment regimens. Many have failed, but many others have produced significant gains, at least over the study period, with simple ap-proaches such as asking pharmacists to provide patients a little extra information. While some researchers continue to study ideas for motivating patients, others work to improve treatments. Some people, for example, respond poorly to existing medications, so even if patients used existing options perfectly, there would still be a need for more effec-tive options. The biggest need, however, appears to be medications that promote compliance by making treatment regimens less arduous and more tolerable. Only real-world use will show if Toujeo and Afrezza meet that second need, but there are several reasons for hope. For one, the reduction in nocturnal hy-poglycemia associated with using Toujeo rather than Lantus is reasonably large. A meta-analysis of 3 of the drug’s phase 3 trials found a 31% reduction in such reactions among 2476 patients (risk ratio, 0.69; 95% CI, 0.57-0.84; P = .0002). While the biggest original selling point for Lantus may have been the relatively low rate of nocturnal hypoglycemia, low blood sugar remains a serious problem. Hypoglycemia is the primary cause of roughly 282,000 emergency department visits each year,9 and many patients fear it enough to risk high blood sugar by taking less insulin than their doctors prescribe. Thus, the lower nocturnal hypoglycemia incidence associated with Toujeo could produce 2 distinct benefits for patients who switch from Lantus: - a reduction in hypoglycemia among those who always used a full dose, and
- a reduction in hyperglycemia among those who only begin taking a full dose after the switch. (Sanofi’s inability to advertise the lower hy-poglycemia risk in the United States may curtail its potential for improving compliance here, but Toujeo’s relative safety may improve patient behavior in Europe, where the ap-proved label mentions the reduc-tion in nocturnal hypoglycemia.
Another potential advantage for realworld patients who switch from Lantus is Toujeo’s greater length of action. The older medication barely lasts 24 hours, so patients must inject themselves promptly or risk high blood sugar. Toujeo’s (as yet untested) longer action will theoreti-cally improve outcomes by protecting oc-casionally tardy users from themselves. Afrezza’s trial performance suggests that it, too, may benefit real-world pa-tients in subtle ways that Sanofi cannot advertise, but its main selling point is obvious to anyone who has ever endured an injection. While research indicates that needles rank among the biggest barriers to treatment compliance in diabetic patients, opinions vary wildly about the market for alternatives that are inhaled rather than swallowed. Some wonder who wouldn’t want to inhale medication rather than inject it. Others say that the failure of Pfizer’s Exubera proves the answer is “nearly everybody.” (Pfizer lost $2.8 billion on the product before pulling it from the market in 2007, just a year after launch. Its reception was so brutal that large drug companies abandoned all work on inhal-able insulin. Afrezza was developed by a much smaller firm called MannKind.) “ Exubera failed because it came via a large and odd-looking device that was hard to carry and embarrassing to display. If you took the thing out at a res-taurant to get some insulin before you ate, people might turn and stare be-cause it looked like you were smoking pot from some sort of unique bong,” said Mark Peyrot, PhD, a sociology professor at Loyola University of Maryland, in an interview with EBDM. Peyrot studies the psychological aspects of diabetes. “ Afrezza is totally different. The device it comes in looks like an inhaler that is used to deliver asthma medication,” Peyrot told EBDM. “I’m not predicting this single improvement guarantees it will become a blockbuster, but there’s no reason to think Exubera’s performance dooms it.” To the contrary, Peyrot thinks that many patients yearn for an injection re-placement (that doesn’t look like a bong) and that the new delivery system may significantly increase the wilingness of its users to take rapid-acting insulin with meals. “ Only a small percentage of people are truly terrified of injections, but many feel some visceral aversion to them, and that’s only the beginning of the problem,” Peyrot said. “People find needles embarrassing and don’t want to inject themselves with a needle in front of others, so they often find themselves doing it in toilet stalls, which are the last place on earth they want to use something that’s supposed to be sterile. Besides, injections can hurt.” Despite the previous failure of inhalable insulin, there is some evidence in the track record of insulin pens that alternative delivery systems can attract large numbers of uses and improve in-sulin adherence. Insulin pens improve upon vial-syringe-needle systems in a wide variety of ways. They provide users with a quicker and more discreet way to inject themselves. They’re easier to carry around. They improve dosing accuracy. They eliminate the need for injection technique. They even tend to hurt less. These advantages have attracted significant user numbers in almost every wealthy country around the world except for the United States, where their adoption among insulin users may still be under 10%. People who do try pens tend to prefer them. More importantly, pens seem to promote treatment adherence. A study of more than 1800 patients concluded that use of one company’s pen (rather than a syringe) was associated with a 39% greater odds ratio (OR) of maintain-ing a medication possession ratio of 0.80 or higher over a 12-month follow-up period (OR, 1.385; 95% CI, 1.037-1.849). A recent review of compliance research found 4 pen-user studies, all of which re-ported significant compliance benefits. And pen design keeps improving. Sanofi said the pen that comes with Toujeo requires less application force and less hold time than the model that comes with Lantus. Such incremental improvements seem unlikely to change patient behavior as much as the transition from injec-tor to inhaler, but it’s still unclear what impact, if any, that transition will have. Afrezza hasn’t been on the market long enough for anyone to study its effects in real-world usage. Sanofi and MannKind are planning post launch research, however, because any evidence that Afrezza significantly increases adherence and outcomes will surely boost sales and justify the product’s considerable price premium: $7.54 per day compared with $3.14 for Apidra. (The effective price premium for Toujeo remains unclear, as the drug retails for the same price as Lantus, but Lantus biosimilars have yet to hit the US market and begin price competition.3) Even after real-world performance data do become available, the costeffectiveness of the new drugs may redmain unclear. Experts still argue about whether actual health benefits justify the price we pay for Lantus and other analogue insulin formulations that have been around for many years. Some say there’s little evidence that the (relatively) new products control blood sugar any better than far older products and argue that their few indisputable advantages, like the reduced chance of hypoglycemia, could be duplicated via strategies that cost billions less, like having a snack before bed. Others argue that the benefits of analogue insulin treatments tend to be hard for trials to measure. For example, analogue formulas can save patients several shots per day, which boosts compliance in real life but not in trials. Analogues also hold blood sugar levels much steadier than human insulin, which has no effect on A1C reduction but may prove a major long-term benefit. Experts may still be having the same argument a decade from now, but as-suming that no one discovers an actual cure for both types of diabetes, the slow but steady parade of new treatment options will continue, offering hope to both physicians and analysts.
|
|
|
Post by compound26 on May 26, 2015 12:59:55 GMT -5
The following article seems to confirm that Afrezza has a role in improving the performance the current AP systems. Diabetes Technology Inches Closer To An Artificial Pancreas www.npr.org/sections/health-shots/2015/01/30/382172052/diabetes-technology-inches-closer-to-an-artificial-pancreasJANUARY 30, 201511:22 AM ET MIRIAM E. TUCKER Every person who uses insulin to manage diabetes wants what they don't have — a replacement for their malfunctioning pancreas. And though the technology isn't yet to the point of creating an artificial pancreas, it's getting a lot closer. Just last week, the U.S. Food and Drug Administration approved a mobile app-based system that can monitor a person's sugar levels remotely. Parents can monitor a child's sugar while she or he is in school, for example, providing greater peace of mind. That technology is the latest step in an evolution aimed at letting people manage diabetes without the burden of calibrating insulin doses themselves. So far we have devices that deliver insulin and devices that continuously monitor blood sugar. Getting those two pieces of equipment to talk to each other would make the process safer and simpler. That's the technology that people really want. And that's starting to happen. Because that technology is rolling out bit by bit rather than all at once, it makes more sense to call it an artificial pancreas "system," according to Aaron Kowalski, chief mission officer and vice president for research at the Juvenile Diabetes Research Foundation (JDRF), a top funder of research into the systems. The devices are "trying to replace mechanically what's lost in diabetes," Kowalski tells Shots. The healthy human pancreas is an awesome machine, secreting the exact right amount of insulin into the bloodstream to allow the glucose from your food to enter your cells and be used for energy. When you eat, your pancreas secretes more insulin. When you exercise, it dials back the insulin. And if you don't eat for a long time, it makes another hormone called glucagon that tells your liver to put more sugar into your bloodstream. If you don't have diabetes, that system keeps your blood sugar within a very tight range. In people with Type 1 diabetes and some with longstanding Type 2 diabetes, that system is broken and the insulin has to be replaced manually, by shots or a pump. Insulin pumps, which have been available for decades, deliver insulin via a small catheter inserted under the skin throughout the day, but the wearer has to tell it how much and when. Getting it right all the time can be extremely difficult, because pump wearers have to check their blood sugar, make educated guesses about the amount of carbohydrates they're eating and how much they exercise, and set the pump accordingly. Essentially, it's trial and error. And even if you get an on-target blood sugar value once, the next day might turn out differently because you exercise or eat more or less or get sick or stressed or, as one patient quipped, "the moon was full." Enter continuous glucose monitors. Available for home use for the past decade, these devices are a huge advance. They automatically measure the wearer's glucose level every few minutes and wirelessly display the value, so wearers can see their sugar level trends at all times. The CGMs can also send out alarms when sugar levels go too high or too low. Many people now wear both a CGM and a pump, but that's not a true artificial pancreas system because the user still has to be the brain. New devices are starting to take on more of that responsibility. A system that shuts off the pump if the wearer's glucose level hits a preset low threshold was approved by the FDA in 2013. The Minimed 530G with Enlite from Medtronics Diabetes helps people avoid low sugars that can cause brain damage or death, and has allowed many parents of a child with diabetes to finally be able to sleep through the night without waking every few hours to check their child's levels. Even better would be a device that predicts when a person's blood sugar will get too low, and intervenes. That's exactly what 4-year-old Xavier Hames of Perth, Australia, got earlier this month. The device shuts off the pump when the CGM predicts that the blood sugar is about to drop too low, reducing the total number of dreaded low blood sugar episodes by almost 80 percent. That device, Medtronic's Minimed 640G with Smartguard, was hyped in news accounts as an "artificial pancreas," but it's not a fully automated system that will keep the boy's blood sugar normal all the time without any input from his parents. Yet Kowalski says the device's ability to prevent low blood sugars is "pretty huge." So far, the 640G is only available in Australia, but it's being tested in the United States, with the aim of future FDA approval. Still, neither of these systems addresses high blood sugars, which over time can damage the eyes, kidneys, heart and nerves in people with diabetes. In 2017, Medtronic plans to add a feature to dose insulin if glucose levels rise above a certain threshold. Further improvements on the technology are in clinical trials. These include: "hybrid" systems that are automated except that the wearer has to signal that he or she is about to eat; "closed-loop" systems that don't require such input; and a fully automated system that adds glucagon in addition to insulin. This last one, which the investigators call a "bionic pancreas," is a bit controversial in the field; some doctors think a functional artificial pancreas system can be achieved without adding the extra hormone, which is less stable than insulin. In the meantime, some tech-savvy members of the Type 1 diabetes community aren't waiting for trials or FDA approvals, having figured out how to "hack" their devices to create their own artificial pancreas systems. All of this is happening rapidly, but challenges still need to be overcome: For one, the insulin needs to be redesigned to work faster in order to prevent post-meal sugar spikes — after all, it's still being deposited under the skin, rather than directly into the bloodstream the way a healthy pancreas does it. Also, CGM accuracy needs to improve. Because the devices measure sugar in the tissues rather than the blood, it's not an exact match. Progress is being made on both fronts. And there's progress on the payment side, too. A Medtronic rep tells Shots that both the MiniMed 640G and the MiniMed 530G are priced similarly to previous systems. Insurance coverage varies greatly by country, of course, and also within the U.S. by insurance plan. The company contracts with more than 600 insurance plans nationwide. There is one glaring coverage gap: Medicare currently doesn't reimburse for CGMs, meaning that wearers have to give up the devices when they hit 65 or pay for them out of pocket. The JDRF and other organizations are lobbying for legislation to fix that. (Medicare does cover insulin pumps, but largely for people with Type 1.) Ultimately, though, even if artificial pancreas technology evolves to the point of full automation, it's still a machine. It can break. And it's not a cure. Last October, researchers at Harvard announced that they had found a way to coax human embryonic stem cells into making insulin. The researchers are now working on encapsulating those cells so that they won't be attacked by the patient's immune system, the process that causes Type 1 diabetes in the first place. Other research is also focused on finding biological "cures." Kowalski sees artificial pancreas systems as a bridge until a biological cure becomes available. "Ultimately, we want to get rid of the devices. But in the meantime, we want to keep people healthy and ease the burden. So that's what we're trying to do: make smarter pumps until we have more nature-made solutions."
|
|
|
Post by compound26 on May 26, 2015 12:33:10 GMT -5
Based on the results quoted in the article below, it looks like Dr. Damiano is getting very good results for his AP system. One wonders, based on the comments in the JDRF video (in the video, the commentator states that use of Afrezza as a mealtime bolus in conjunction with an experimental AP system "works really really well".), if Dr. Damiano incorporates Afrezza into his AP system, will his results be even more impressive?Bionic Pancreas Gets Prime Time Slot at AACE www.medpagetoday.com/MeetingCoverage/AACE/51551A year-long trial is the next test for the device, developer says. by Parker Brown Staff Writer, MedPage Today NASHVILLE -- The developer of a bionic pancreas came here to deliver good -- if early -- news, and he did just that before a rapt audience. E dward Damiano, PhD, of Boston University, revealed the partial results at the annual meeting of the the American Academy of Clinical Endocrinologists and said that his team is planning a large, year-long, randomized trial of the device. The artificial pancreas -- which automatically regulates insulin levels and dispenses glucagon and insulin according to an algorithm -- improved glycemic control and led to less hypoglycemia in a small, short-term trial of adults and in a separate trial of pre-teens. "We want a technology that adapts to the spontaneity of life," said Damiano, who added that the device could change the way type 1 diabetes patients care for themselves until a cure is found. "It does this while simultaneously unburdening people from management decisions and worrying about being wrong." The Study
Damiano was the first speaker at this year's AACE conference -- probably the first biomedical engineer to lead an AACE conference -- said Mack Harrell, MD, the president of AACE. And he played that novel role well: dressed in black shirt and jeans, he paced the stage, liberally using terms like "synergy" and "integration" and topping his presentation with a high-production-value marketing video that touted the bionic pancreas. He also shared pictures of his son -- who at 11 months was diagnosed with type 1 diabetes. Damiano was channeling Steve Jobs, not Arnold A. Berthold. But he also had results from two trials to report. In the first trial, 19 pre-teens at a summer camp in 2014 wore either the device or had normal care for 5 days. In the control group, the mean continuous glucose monitor (CGM) was 168 ± 30 mg/dL; for the group with the device, the mean CGM was 137 ± 11 mg/dL. The time spent under 60 mg/dL was 2.8% of the time for the control group, and 1.2% for the intervention group. Time over 180 mg/dL was 36% versus 17%. In the separate trial, Damiano and his colleagues enrolled a group of 38 adults, seven of them in the control group, for 11 days. The patients were at four different medical centers around the country. Those in the control group had a mean CGM of 162 ± 29 mg/dL versus 141 ± 10 mg/dL for the group with the device. Time spent under 60 mg/dL was 1.9% versus 0.6%, and 34% above 180 mg/dL versus 20%. In both of the studies, the same amount of insulin was used. The device is an amalgam of several different parts: a Dexcom monitor, two Tandem infusion pumps, and an iPhone accessible algorithm -- the user carries the phone. Damiano said he tested kids at summer camp because their active lifestyle would test not only the algorithm, but the durability of the device itself. "They're not exactly showing proper respect to this device," he said. But Is It Safe?
"You have to realize that there are circumstances in which things can really go wrong," said Damiano, speaking of the safety and security of the device. "And that you're dealing with a very vulnerable population." In addition to the possibility of glitches or malfunction, app-based medical devices must also worry about cybersecurity. A recent study found that the majority of insulin dosing apps are unreliable and put patients at risk. Nearly a quarter of these apps crashed. Two-thirds carried a risk of giving the wrong dosage recommendations, and there was a lack of transparency with most of the apps. The software on a fully automated bionic pancreas would have to be much more reliable. And a study by Yogish Kudva, MD, from the Mayo Clinic, and colleagues, found thatcybersecurity is not where it should be for artificial pancreases. "We suggest that, to date, the essential concept of cybersecurity has not been adequately addressed in this field," concluded the authors of that paper. Damiano said he agreed. "I don't think in the med device industry that has been handled particularly well," he said during a press conference here. "We have a lot of strategies for that, but I think we're really going to have as cybersecure a system as we can hope to have with the technology that there is now." He added that they've hired a security expert to help them. Upcoming Study
The next step is a longer, randomized trial, said Damiano. They are working on a proposal for a year-long study of 480 participants, 160 of whom will belong to a control of usual care. There will be no remote monitoring of the patients, and the primary outcomes will be HbA1c levels and mean CGM levels. The current plan is to include patients more than 10 years old, said Damiano, though he would like it to be for ages 6 and above. "The FDA is really encouraging us to push that number down," he said. "They want to test it with as many people as possible. If we do a trial with 2- and 3-year-olds, that's going to give them peace of mind." He said the FDA has been cooperative, contradicting their image that the agency is slow to react. "They're taking a very different attitude from what people have expected them to do," he said. Damiano and his team must build a single device in which all of the components come together in order to move forward. He said that they are working with industry to design the device. He added that it will be at least 3 years before the device is available. When asked to speculate about the cost, he said it would be slightly more expensive than current devices because it needs two chambers -- one for insulin and one for glucagon -- at around $8,000 to $9,000. Damiano disclosed relevant relationships with Dexcom, Lilly, and Tandem Labs.
|
|
|
Post by compound26 on May 22, 2015 14:44:57 GMT -5
And here's the reply (that was quick!): Thanks, liane. That's pretty fast response from Matt. Shareholder friendly. Like that.
|
|
|
Post by compound26 on May 22, 2015 13:56:10 GMT -5
Honestly, I thought I heard 4500. But now that I've seen numerous people question this, maybe he said 4 to 500 employees. Might be worth a confirmation from Matt. Thanks, liane. I think most likely Matt meant to say 4 to 500 employees. 4,500 employees does not make sense given that we all understand the production is supposed to be highly automated.
|
|
|
Post by compound26 on May 22, 2015 13:50:31 GMT -5
Is he quoted accurately? "Pfeffer noted that the company has about 225 employes working at the Danbury facility. Once the plant is at full capacity, the company would need about 4,500 employees, he said." What on earth? I had the same feeling. So I highlighted the numbers for consideration by you guys. For your consideration, if we have to add 4,200 people, at $100,000 per person per year, that will come to $420 million, at $75,000 per person, that will come to $315 million. So hopefully that was a misquote (or typo) and 4,500 employees was really meant to be 450 employees. For your consideration, if we have to add 225 people, at $100,000 per person per year, that will come to $22.5 million, at $75,000 per person, that will come to $16.875 million. Can someone who were at the meeting clarify on this point?
|
|
|
Post by compound26 on May 22, 2015 13:19:44 GMT -5
savzak and tchalaa, many thanks for posting the story and the links. Very helpful. I encourage fellow members of this board to visit newstimes.com to read the story. In addition to the story that we quoted here, it also has 19 photos of the Mannkind annual shareholder meeting, which include photos of Al, Hanka, Matt, the individual shareholders named in the story and the production facilities. Therefore, for those who were not able to make to the meeting itself, it appears to be a pretty good report of the meeting. I have edited the story a little bit for easier reading. www.newstimes.com/local/article/Mannkind-investors-raise-stock-manipulation-6279751.phpMannkind investors raise stock manipulation allegations
Dirk Perrefort Published 8:17 pm, Thursday, May 21, 2015 DANBURY -- Investors who are bullish on Mannkind expressed frustration Thursday during the company's annual meeting that executives aren't doing more to address the significant short positions on the stock and efforts to manipulate the stock price. One investor went so far as to ask the company why executives haven't filed a complaint with the Securities and Exchange Commission on short investors who have been openly bashing the stock through national media outlets, including CNBC. "I'm not going to name names, but these are people with an agenda who are spreading lies about the company, and nobody is challenging them," said Michael Moss, one of the more vocal investors during Mannkind's annual shareholder meeting in Danbury on Thursday. Moss, who traveled from Florida for the meeting, noted that the company has the fifth-largest short position on Nasdaq with more than 103 million shorts as of last week. He added that there are probably about 200 million shares in play in the market after subtracting shares held by company executives. Matt Pfeffer, the company's chief financial officer, said company executives are equally frustrated by the attacks against the company, adding that those who respond to such attacks are usually fighting a losing battle. "We've heard a lot about the short selling, but we just don't have the tools available to us to see if that's true," he said. "But we believe it may be true." Mannkind received FDA approval in February for Afrezza, an inhalable form of insulin that many believe is a game changer for diabetic treatment. Since then, the stock has been on a roller coaster, reaching close to $8 per share after the FDA announcement. On Thursday, the stock closed at $4.63 per share. Seeking promotion
Investors also expressed concerns at the meeting that Sanofi, the company's marketing partner for Afrezza, hasn't done enough to publicly extoll the virtues of the drug for the diabetic community. "When is the CEO of Sanofi going to stand up and start promoting Afrezza?" asked Ken Poli, one of the many investors to attend the meeting. "That's the kind of messaging we need to fight these shorts." Many of the investors who attended the meeting, which was held at the company's manufacturing facility on Taylor Avenue, were also suffering from diabetes or who have loved ones with the illness. Anyone who has used the drug, they said, is amazed at the results. Hillard Saveth, a financial adviser from Long Island, said his glucose levels would typically spike to 160 after meals. But after using Afrezza, he said his doctors were amazed to see his levels never surpassed 140. "When I walked in today, I saw the bagels and thought to myself, I'd love to eat one of those," Saveth said. "Instead of having to go to the bathroom to inject myself, I simply used my inhaler. Then I ate a bagel." Gerry Roberts, a shareholder with Type II diabetes, traveled all the way from Ireland for the meeting to personally thank Al Mann, the company founder, for investing millions of dollars to bring the drug to market despite some early setbacks. He also asked when it would seek regulatory approval in Europe for the drug. " I believe I'm a prime candidate for Afrezza and it would improve my life significantly," he said. Pfeffer said Sanofi is currently reviewing what parts of the world it can get a quick introduction into the market. "They are still assessing," he said. " But by July or August, we should have a report of the best opportunities." Other uses Pfeffer also said Mannkind executives are in discussions with other companies about other potential uses of the Technosphere particle that Afrezza uses to deliver the insulin to the lungs. Mike Calorossi, the company's director of manufacturing, said the Techosphere particle can be easily manipulated by the company to serve as a delivery vehicle for other drugs, including pain management and migraine medication. While current migraine medication can take up to an hour before it enters the patient's bloodstream, Calorossi noted, that with a Technosphere delivery, the drug could be in the patient's bloodstream in less than 10 minutes. "There is a lot of potential out there for this particle," he said. The particle, he said, also leaves the patient's system quickly without any known side effects. Pfeffer noted that the company has about 225 employes working at the Danbury facility. Once the plant is at full capacity, the company would need about 4,500 employees, he said. "Hopefully in the coming years, we will be the biggest employer in Danbury," he said. "And based on what our product can do, I think we'll get there." dperrefort@newstimes.com; 203-731-3358; www.twitter.com/DirkPerrefort
|
|