03/25/2015 | 01:49pm US/Eastern
By a News Reporter-Staff News Editor at Journal of Engineering -- From Alexandria, Virginia, VerticalNews journalists report that a patent by the inventor Von Schuckmann, Alfred (Kevelaer, DE), filed on November 27, 2012, was published online on March 17, 2015.
The patent's assignee for patent number 8978646 is Sanofi SA (Meyrin, CH).
News editors obtained the following quote from the background information supplied by the inventors: "An inhaler of the generic type is described in U.S. Pat. No. 5,429,122. There, the amount of the substance to be delivered is transferred from a lower storage chamber to an upwardly movable dosing chamber. The dosing chamber is in the form of a ring-shaped groove in (or on) a linearly movable rod which is spring-loaded. A mandrel in the closure cap presses the rod into a retracted (lower) position. When the patient removes the cap, the rod is propelled rapidly upward into a ready-to-empty transfer position. The contents of the dosing chamber are advanced into the mouthpiece via a suction air stream created by the patient. A drawback is that the spring-loaded rapid upward propulsion of the rod tends to provide an incorrect dosage of the substance."
As a supplement to the background information on this patent, VerticalNews correspondents also obtained the inventor's summary information for this patent: "It is accordingly an object of the invention to provide an inhaler for powdery, in particular medicinal, substances which overcomes the above-mentioned disadvantages of the heretofore-known devices and methods of this general type and which provides for an inhaler of simple construction which delivers into the transfer position a reproducibly uniform dose, ready to be delivered, when the closure cap is removed.
Receptor-mediated inhibition of small bowel migrating complex by GLP-1 analog ROSE-010 delivered via pulmonary and systemic routes in the conscious rat.
BACKGROUND: ROSE-010, a Glucagon-Like Peptide-1 (GLP-1) analog, reduces gastrointestinal motility and relieves acute pain in patients with irritable bowel syndrome (IBS). The rat small bowel migrating myoelectric complex (MMC) is a reliable model of pharmacological effects on gastrointestinal motility. Accordingly, we investigated whether ROSE-010 works through GLP-1 receptors in gut musculature and its effectiveness when administered by pulmonary inhalation.
MATERIALS AND METHODS: Rats were implanted with bipolar electrodes at 5, 15 and 25 cm distal to pylorus and myoelectric activity was recorded. First, intravenous or subcutaneous injections of ROSE-010 or GLP-1 (1, 10, 100 μg/kg) with or without the GLP-1 receptor blocker exendin(9-39)amide (300 μg/kg·h), were studied. Second, ROSE-010 (100, 200 μg/kg) Technosphere® powder was studied by inhalation.
RESULTS: The baseline MMC cycle length was 17.5±0.8 min. GLP-1 and ROSE-010, administered intravenously or subcutaneously, significantly inhibited myoelectric activity and prolonged MMC cycling; 100 μg/kg completely inhibited spiking activity for 49.1±4.2 and 73.3±7.7 min, while the MMC cycle length increased to 131.1±11.4 and 149.3±15.5 min, respectively. Effects of both drugs were inhibited by exendin(9-39)amide. Insufflation of ROSE-010 (100, 200 μg/kg) powder formulation totally inhibited myoelectric spiking for 52.6±5.8 and 70.1±5.4 min, and increased MMC cycle length to 102.6±18.3 and 105.9±9.5 min, respectively.
CONCLUSIONS: Pulmonary delivery of ROSE-010 inhibits gut motility through the GLP-1R similar to natural GLP-1. ROSE-010 causes receptor-mediated inhibition of MMC comparable to that of intravenous or subcutaneous administration. This suggests that ROSE-010 administered as a Technosphere® inhalation powder has potential in IBS pain management and treatment.
Compounds which directly inhibit IRE-1α activity in vitro, prodrugs, and pharmaceutically acceptable salts thereof. Such compounds and prodrugs are useful for treating diseases associated with the unfolded protein response and can be used as single agents or in combination therapies.
Intracellular kinase inhibitors and their therapeutic uses for patients with T cell malignancies, B cell malignancies, autoimmune disorders, and transplanted organs.
When a person without diabetes consumes food, the first phase spike of insulin reaches an early peak in the blood in about 10 minutes. That first phase starts the glucose metabolism process. The second phase release of insulin responds to the quantity and timing of the food. Non-diabetics also have a basal release of insulin that occurs continually to support fueling the body between meals. In type 1 diabetes patients, both the first and second phases of insulin release and also the basal release do not occur. In type 2 patients who make up well over 90% of patients diagnosed with diabetes, the first abnormal physiologic problem occurs is the lack of the first phase of insulin release. In diabetes patients exogenous insulin is needed to replace the insulin release that would be provided in a non-diabetic person. Diabetes results when insulin is either not released (type 1) or is not normally released and the person is resistant to the effect of the insulin (type 2). The average healthy adult person releases about 1 unit of insulin each hour as basal insulin and approximately 1 unit of insulin is released for each 10 to 15 grams of carbohydrate consumed.
When a state of insufficient pancreatic insulin occurs, exogenous injected insulin products are available to replace the deficiency. THE PROBLEM is that current available products are not adequate, they are far from being able to replace the deficiency in a natural physiologic manner. The pharmacokinetic/dynamic profile of prandial (mealtime) insulins are much too slow, their activity does not become effective quickly enough and they persist far longer than is needed to control mealtime glucose. The current rapid acting insulin analogs (RAAs), which are the best of the current prandial products, do not reach a peak in the blood for close to an hour and persist for as long #$%$7 hours. To reasonably control the increase of glucose from the meal, the dose of such an insulin should be inconveniently
Afrezza: Treating Diabetes in a Physiologic Manner
R. Keith Campbell, RPh, FAADE, FASHP, FAPhA, CDE,
Distinguished Professor Emeritus in Diabetes Care/Pharmacotherapy,
Washington State University College of Pharmacy
The health care crisis created by the explosion of diabetes worldwide is one of society's greatest challenges.
The IDF projects that the prevalence of diabetes by 2030 will be over 550 million patients worldwide. When one adds in the patients with "Prediabetes,"who presently are not often treated, the impact on health care becomes frightening. Diabetes is a family of diseases that have in common hyperglycemia. Glucose, the main fuel of the body is needed by all cells all of the time. Glucose is supplied to the entire body during meals from ingested food and between meals from glucagon stored in the liver. Insulin is supplied from the beta cells in the pancreas to utilize the glucose for the cells as the glucose levels become elevated. In a healthy person it is provided in two waves, the phase 1 at the first ingestion of carbohydrates and phase 2 to manage the extended glucose level from the meal. In type 1 diabetes the immune system destroys the beta cells and insulin is no longer secreted. In type 2 diabetes, the first phase release is blunted and the patient becomes resistant to the effect of the insulin. Also in type 2 patients, more glucose is released by the liver, incretin (gut) hormones are diminished, the kidney reabsorbs more glucose and glucose levels spike in response to the meal. Excess glucose via several changes in normal physiology create diabetes complications including retinopathy (eye), neuropathy (nerve), nephropathy (kidney) and blood coagulation disorders. Excess glucose combined with hypertension and lipid disorders result in the enhancement of heart disease and a financial burden on health care systems.
The title should read "Test Driving new inhaled insulin Afrezza"
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.
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.
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.
Sanofi chairman says acquisitions not 'indispensable' for future
PARIS (Reuters) - French pharmaceutical company Sanofi has examined acquisitions opportunities but does not view deal-making as "indispensable" to its future, its chairman told French paper Les Echos in an interview.
"We looked at potential deals but found the asking prices to be too high for the businesses," said Sanofi Chairman Serge Weinberg.
"We have opted for a balanced a strategy of innovation and diversification that makes acquisitions not indispensable."
The global pharmaceutical industry has been consolidating in recent years as companies seek to replace drugs that are losing patent protection and renew their pipeline with new products.
Through early March, M&A transactions targeting biotech and pharma companies reached $59.3 billion this year, a 94 percent increase over the same period a year ago and the highest volume for this stage in any year since 2009.
(Reporting by Leila Abboud; Editing by Miral Fahmy)
Toujeo SoloStar mostly covered as Tier 3 incl DoD, preferred Tier 2 by some Cigna. Afrezza is preferred by DoD, some Cigna, Texas Dept of Service. This confirmed Toujeo launch Mon 3/30/15.
The MD-360 Report: FDA Approval of Toujeo Means Afrezza Sales to Ramp Up Rapidly
Published: Monday, 02 March 2015 09:39 Written by Dr. Hung V Tran, M.D., M.S.
As what is seemingly a blessing to the MannKind shareholders and to hundred of million of patients worldwide, the United States FDA approved Toujeo on Friday Feb. 25, 2015.
With the aforementioned key event in placed by nearly five months early, Afrezza and Toujeo to witness a rapid up ramping of sales, much sooner than what the market anticipated was a “controlled launch.”
To gauge at how quickly a resourceful biopharma can catapult its FDA approved drug into a blockbuster, let us examine the case for orlistat.
In 1999, Roche received the Agency marketing authorization for orlistat, to treat patients suffering from overweight and obesity, it took approximately 3-months for the elite Swiss biopharma, to catapult the said drug to blockbuster sales.
Similarly, the French Global Diabetes Powerhouse Sanofi has 35,000 elite sales and marketing professionals, who are enjoying existing relationships with physicians, hospitals and clinics.
This already established infrastructure synergizes growth and decreases the balance sheet metric that is selling general and administrative costs “SG&A.” Therefore, it should not take longer than three months to mass-market Afrezza and Toujeo.
“Toujeo should be available in early second quarter, according to Pierre Chancel, Senior VP, Global Diabetes of Sanofi,” we noted, and continued, “Since Afrezza demands, as reflected by launch enthusiasm, from both clinicians and patients are strong, it is most likely that the said insulin combinations will procure powerful blockbuster sales for the Sanofi-MannKind partnership.”
It is highly likely that the key event, as elucidated, will catalyze earnings growth in epic proportions and to deliver much hope for patients afflicted with diabetes first in the United States.
Later this year, the good news should abound Europe, as Sanofi already filed Toujeo-NDA through the European Medicine Agency.”
We appreciate the FDA for the early approval for Toujeo, as “diabetes is a global killer, rivaling HIV/AIDS in its deadly reach, and is killing more than 4 million people annually. Every 7 seconds a person dies from diabetes-related causes.”
We bid farewell to the MannKind Long and Strong shareholders with a quote from Shakespeare (Julius Caesar Act V), that is also referenced by Philip Fisher, who is considered as the seminal thinker of growth investing.
There is a tide in the affairs of men.
Which, taken at the flood, leads on to fortune;
Omitted, all the voyage of their life
Is bound in shallows and in miseries.
On such a full sea are we now afloat,
And we must take the current when it serves,
Or lose our ventures.
Similar to waves amidst the open sea, share price of MannKind can experience its ups and down temporarily. In the long horizon, it is undeniable that Afrezza-Toujeo are galvanizing much enthusiasm and hopes from Main Street physicians and patients alike, thus, signaling an incoming Tsunami of epic proportion.
Wednesday, Dec. 17, 2014, 11:44 AM Pacific
Pay Rate: Sag Scale + 10%
Usage: Cat II Industrial for drug co website
Conflicts: Afrezza is a type of insulin
Casting Director: Deborah Brown
Interview Dates: After Jan 4
Shoot: Mid January
CLIENT WANTS TO SEE PICTURES BEFORE JANUARY
[ FEMALE ]
Somewhere in between 35-50 years old. Little heavier or just read = real person, not slim but not large Must have nice hands (not beauty or model hands, but nice hands ... think natural) Tan/olive skin = ambiguous ethnicity