Mannkind: A Growing Threat To The Status Quo

[cm5]

Reposting thekindaguyiyam's find below:

The countdown to lift off is accelerating----

4 hours ago thekindaguyiyam said:


Mountain Grove News Journal: Wednesday, May 4, 2016 6:44 am | Updated: 2:30 am, Thu May 5, 2016.

by Jean Louis Selam, M.D.



(NAPSI)—According to the American Diabetes Association, at least a third of Americans will develop the condition at some time in their lives. It can’t be cured but it can be managed.


While medicine has improved the quality of life of people with diabetes significantly over the years, the need for some way to regulate blood sugar remains unchanged. Researchers are exploring new pathways to innovative treatments. For instance, one research team identified a new link between heart hormones, insulin resistance and obesity, which could signal new treatment options for those with type 2 diabetes.


Continued insights into the medical characteristics of the main groups of people with diabetes have unveiled some new methods that doctors can use to correctly identify forms of diabetes sooner. Armed with these, doctors can proactively and more effectively treat once-rare variations of this condition.


One new treatment is an inhalable form of insulin that acts quickly, so users have greater flexibility in managing blood glucose fluctuations that often occur after eating.


This means more spontaneity for people with diabetes. Injected insulin usually needs to be taken 20 to 30 minutes before eating and pills can take longer still. These proven medicines are very important to any diabetes care regimen but they’re not easily adjustable.


The inhalable treatment, called Afrezza, works for most people with type 1 and type 2 diabetes, and it may be especially helpful for many newly diagnosed adults with type 2 who aren’t aware of their options and may forgo treatment due to the overwhelming nature of the diagnosis. Such people should check with a doctor to see if this might help.


It offers three advantages for adults with type 2 diabetes:


1. Few to no injections. Not everyone with type 2 diabetes needs insulin injections, but for those who do, this can lower or eliminate the need.

2. Less paraphernalia. People with diabetes don’t just carry around a vial of insulin; there are syringes, swabs for cleaning injection sites, and more. Many people ration these supplies to make sure the quantities covered by their health care plans will last. This is especially important as the estimated medical costs for people with diabetes are twice as high as for people without diabetes. With a supplemental insulin in the discreet form of an inhaler, people with diabetes can leave more supplies at home and still feel prepared for whatever may come their way.


3. Faster peak action time and shorter duration. Social occasions are often reduced to a game of “unit roulette” for many people with diabetes. With little control over how quickly a restaurant order will arrive or what food will be at a cocktail party, people may find their choices limited, and end up with either too much or too little insulin in their systems. This supplemental treatment bridges the gap between a regular regimen and those special occasions.

All this can give people a sense of control over their condition. Diabetes needn’t be the definition of who a person is. You can live your life fully prepared for the unexpected and in control.

Learn More

For further facts, visit www.afrezza.com.

• Dr. Selam is CEO of the Diabetes Research Center in California and author of several articles on insulin therapy techniques. He has also performed pioneer work on intraperitoneal insulin and insulin-induced remissions.

On the Net:North American Precis Syndicate, Inc.(NAPSI)




www.news-journal.net/online_features/health_and_wellness/article_6fb6e9cd-05a8-583f-a4da-8382ed7d582c.html

"When an idea reaches critical mass there is no stopping the shift its presence will induce."



Marianne Williamson

[cm5]

Time to reread post by pantaloons on April 20, 2016 at 2:37pm.

This has probably been mentioned or alluded to in one form or another numerous times on this board, but I think it's worth mentioning at least one (if not many) more times:



Theoretically, TS threatens every existing BP market where a drug can be effectively administered in the lungs. Allowing Afrezza (or any future TS-delivered drug) to succeed will ultimately harm BP market share, whether it's in 5 years or 20. Partnerships with BPs that could potentially be threatened are not politically or economically favorable.



With a disruptive technology, I think companies need to see far, far beyond the forest.

I think MNKD is starting to do that now.

[agedhippie]

May 5, 2016 21:14:35 GMT -5 cm5 said:

Time to reread post by pantaloons on April 20, 2016 at 2:37pm.

...

How about linking to a post rather than repost the whole thing? Especially when it's a post on this board.

[esstan2001]

Wait, what's that sound I hear?   it's like a low hum, building...

Could it be the start of some more serious journal / white paper / magazine / social media buzz around Afrezza?


Turn up the frequency Kenneth!  

[laffs4sale]

So Afrezza is a growing threat to the status quo but scripts fall every week and the company is almost out of money. What is the color of the sky in your world?

[als57]

To speed up the transition to Mannkind marketing Afrezza, why doesn't the company buy the remaining Afrezza from the rats at Sanofi?

Seems that the company would not be "hung out on the yardarm till July 4th or longer.  Company already is printing new packaging, so insertion could be possible.  Or with all the "bucks" being spent on "new suits" disposal would be an option to gain earlier freedom.

[agedhippie]

May 7, 2016 13:59:04 GMT -5 als57 said:

To speed up the transition to Mannkind marketing Afrezza, why doesn't the company buy the remaining Afrezza from the rats at Sanofi?

Cost and the ability to distribute it. Right now the best option is to let Sanofi keep servicing the demand while the infrastructure to handle the sale and distribution is put in place by Mannkind. Sanofi are selling Afrezza because they are contractually obliged to, not because they want to.

[Deleted]

May 5, 2016 21:14:35 GMT -5 cm5 said:

Time to reread post by pantaloons on April 20, 2016 at 2:37pm.

This has probably been mentioned or alluded to in one form or another numerous times on this board, but I think it's worth mentioning at least one (if not many) more times:



Theoretically, TS threatens every existing BP market where a drug can be effectively administered in the lungs. Allowing Afrezza (or any future TS-delivered drug) to succeed will ultimately harm BP market share, whether it's in 5 years or 20. Partnerships with BPs that could potentially be threatened are not politically or economically favorable.



With a disruptive technology, I think companies need to see far, far beyond the forest.

I think MNKD is starting to do that now.

Becoming is superior to being.

—Paul Klee

[mbseeking]

Posted this a little while ago, but seems to fit here too...

It's so hard to keep your focus on the big picture when you've lost money on a bet. In my case, a lot.

But as we struggle with this innovation the news on diabetes gets worse and worse. Much so actually. It is not an epidemic, it is an existential cataclysm in waiting.

www.sciencemag.org/news/2016/04/obesity-rates-skyrocket-china-s-rural-kids. Do you think China , and the majority of other countries of the world will be able to set up an endocrinologist network to manage titration of injectable insulin or the other complex drugs to save these people when diabetes develops? Or safely administer multiple daily insulin injections?

Do you think they will be able to re-educate and rollback diets so the cause of the obesity goes away? That genie can be put back in the bottle?

Or do you suspect, as I do, the largest hope , by far, will be an easy to administer insulin puffer.

Folks, the potential market for Afrezza is astonishingly larger than we think it is today. Let's not get lost in the weeds on a little dilution on the road to that.

[agedhippie]

Jun 19, 2016 9:09:00 GMT -5 mbseeking said:

www.sciencemag.org/news/2016/04/obesity-rates-skyrocket-china-s-rural-kids. Do you think China , and the majority of other countries of the world will be able to set up an endocrinologist network to manage titration of injectable insulin or the other complex drugs to save these people when diabetes develops? Or safely administer multiple daily insulin injections?

Do you think they will be able to re-educate and rollback diets so the cause of the obesity goes away? That genie can be put back in the bottle?

Or do you suspect, as I do, the largest hope , by far, will be an easy to administer insulin puffer.

Folks, the potential market for Afrezza is astonishingly larger than we think it is today. Let's not get lost in the weeds on a little dilution on the road to that.

They are talking about Type 2 so this will largely be treated by Metformin and oral meds, not insulin. When/if they progress to insulin it will be to NPH and maybe Regular later if needed simply because of cost - this is rural China we are talking about here. They don't need an endo network to treat Type 2, they will simply train their doctors to manage it as a point solution much as we do in the US.

There may be a market in China, but it's not in the countryside.

[mbseeking]

Agedhippie.. You may be right, its hard to tell. If MNKD can survive the short run , then anything is possible. Afrezza has the potential to be a true gamechanger IMO. That's why I'm investing. I'm not a medical professional but it seems that diabetes treatment protocols are pretty old. A few years down the track and some studies might show that early intervention of a ultra fast easy to apply insulin stops the progression of pre diabeties to full blown t2. Now that might prompt a change in treatment protocol. Sure it will be too expensive for farmers in china. .but in 5-10 years if mannkind is successful they might chose to license it to manufacturers in the emerging world who can do it for a lower cost. And I'd be ok with that. I'd have made some money and this wonderful invention might help to improve the lives of 00's of millions.  Investing doesnt get any better than that.

[centralcoastinvestor]

If Afrezza succeeds in the market place after launch 2.0, MannKind could have one of the deepest drug pipelines in medical history.  The list of current medications that could be made more effective by improved speed of action is almost limitless.  For instance, today I am dealing with vertigo, which is a dizziness that comes on for no particular reason and without warning.   I take meclizine to counteract the dizziness.  However, it takes approximately one hour to begin working and can make me a little drowsy.  If we could load meclizine onto a Technosphere partical and I could inhale it, then I could see relief perhaps in 10 minutes possibly without drowsiness.  I know most everyone has seen the long list of possible applications for Technosphere.  MannKind lacks the cash to go forward with many other drugs besides Afrezza at this point.  I think the long standing short attack (siege) has been intentional to starve MannKind of cash.  Someday, when MannKind has a billion dollars in the bank, I figure their pipeline will have at least 20 candidates.

[gamblerjag]

Hey  CCI,    Good post, as always!  I also experience Vertigo, fortunately for me it happens only ever few years but it is debilitating when it happens.  Lets hope 2.0 leads to all these good possibilities.  Happy 4th to all.  well except bashers!  that hate Afrezza.. just to hate.

[cm5]

Seems that many are distracted by simple complexities (yes, oxymoron, meaning obvious/expected technical/timing difficulties)
of the new roll out of Afrezza for July 25, 2016. 

Time to remind all again of what is possible with Afrezza---in particular, in reference to IDE's, Insulin Degrading Enzymes.

Clinical and epidemiological studies have found that type 2 diabetes, and hyperinsulinaemia, increased the risk of developing Alzheimer's disease (AD) in the elderly.

The link between hyperinsulinaemia and AD may be insulin-degrading enzyme (IDE). This enzyme degrades both insulin and amylin, peptides related to the pathology of type 2 diabetes, along with amyloid-β peptide (Aβ), a short peptide found in excess in the AD brain.

Read more: mnkd.proboards.com/thread/5870/ides-insulin-degrading-enzymes#ixzz4EhPjErBr

An excessive and indirect stimulation of IGF-1 receptor due to sustained and chronic hyperinsulinemia over the therapeutic level required to overtake acute/chronic insulin resistance may act as endocrine disruptor as it may possibly increase the cardiovascular risk in the short and medium term and mitogenic/proliferative action in the long term.

Read more: mnkd.proboards.com/thread/5870/ides-insulin-degrading-enzymes#ixzz4EhP8S9ds

[cm5]

Time to refresh focus on the fact that Alfred Mann's wisdom, brilliance about inhaled monomeric human insulin, Afrezza, with Technosphere will exponentially improve world health, while reducing health care costs.

We continue to be distracted by the posts of naysayers/fudsters as well as inappropriately impatient about the realities of navigating the shark filled shallows and depths of the choppy seas of typical regulatory oversight as well as the "random" rogue wave created by insider fraud/hedge fund/algorithm/manipulated "market maker" churning, all of which is based upon greed and fear of loss of market/income/power/control. 

There have been many fine posts, in particular by mnholdem and peppy, but now is good time to point out the fundamentals yet again why we remain driven to see Mannkind become the game changer. Take the long view, as did Alfred Mann. Alfred Mann was the beyond brilliant man who could see the entire elephant from above, in it's habitat and it's place on our beautiful blue planet, while the  blind fumblers,small minded and greedy play games with lives stalling the inevitable success of Mannkind, for short term amoral gain counting coin.

Read this Mannkind patent again carefully. If no time/interest in detailed reading, just go to the highlighted areas for overall view. Go to the patent link to find the references.

Method of reducing serum proinsulin levels in type 2 diabetics

US 20050153874 A1

ABSTRACT

Methods are provided for reducing serum proinsulin levels, lessening post-prandial pancreatic stress, and reducing risk factors for atherosclerosis in subjects with diabetes mellitus, type 2. The method includes administration of insulin in a manner that mimics the meal-related first phase insulin response, using a dose sufficient to reduce serum levels of proinsulin. In some embodiments of the method insulin administration is commenced early in the course of the disease. Mimicking first phase kinetics, peak serum insulin levels can be reached within about 18 minutes of administration. In increasingly preferred embodiments peak serum insulin levels can be reached within about 15, 12, or 10 minutes of administration. Serum insulin levels return to baseline within about two hours of administration.

Publication date Jul 14, 2005  www.google.com/patents/US20050153874

BACKGROUND OF THE INVENTION

[0003]

Diabetes mellitus is present in 17 million Americans. Its prevalence is growing at a rate of 4.5% per year, particularly diabetes mellitus type 2, also variously called adult-onset and insulin-resistant diabetes. The paradigmatic defect in diabetes is the mis-regulation of serum glucose levels. In addition to the deleterious effects of hyperglycemia, inability to properly respond to high serum glucose levels creates stress on the pancreas that can accelerate progression of the disease in type 2 diabetes. Also, the diagnosis of diabetes carries a 2 to 4 times greater risk of stroke and heart attack in individuals with the disorder. The presence of diabetes in an individual without known heart disease places their risk of new myocardial infarction at the same level as a person who has already had a myocardial infarction but who does not have diabetes. Thus there are important therapeutic goals in the treatment of type 2 diabetes in addition to hyperglycemia per se that are not adequately addressed by currently available treatments.


It is therefore an object of the present invention to provide alternative treatments, especially treatments for type 2 diabetes

Diketopiperazine microparticle drug delivery systems are used in various embodiments of the method. In further embodiments of the method, the insulin is administered by pulmonary delivery using synthetic biodegradable polymeric or diketopiperazine microparticles incorporating the insulin. In preferred embodiments, delivery is achieved by inhalation of a dry powder. In aspects of the method utilizing diketopiperazine microparticles, fumaryl diketopiperazine is a preferred type of diketopiperazine, the insulin is dimeric or monomeric, and preferred dosages are in the range of about 15 to 90 IU or greater than 24 IU of insulin. In preferred embodiments, inhalation of the dry powder is facilitated by use of a unit dose inhaler. Embodiments of the method reducing risk factors for atherosclerosis include ones wherein the risk factor is LDL particle size and LDL particle size is increased; and wherein the risk factor is plasminogen activator inhibitor type-1 (PAI-1), and PAI-1 expression is reduced, using the method of administration and formulations described herein.

The ideal kinetics of insulin formulations for prandial substitution include a rapid and early onset of action and a duration of action long enough to cover meal-related glucose absorption. One problem with existing formulations of insulin for subcutaneous (s.c.) injections has been the unpredictable variability of absorption, exceeding 50% in some cases, and the relatively slow rise in serum insulin levels compared to physiologic meal-related first phase insulin response, in which serum insulin levels can peak by about 6 minutes.

Meal-related first phase insulin originates from storage vesicles in the beta cells of the islets of Langerhans of the pancreas, where proinsulin undergoes enzymatic cleavage into insulin and C-peptide. Type 2 diabetes, as distinct from type 1, is characterized by a loss of the meal-related first phase insulin response. This loss occurs early in the disease process. Type 2 diabetes, again as distinct from type 1, is further characterized by elevated levels of serum proinsulin. Such circulating intact proinsulin (iPi) likely signifies that insulin requirements exceed beta cell capacity, causing pancreatic stress leading to premature release of the storage vesicles

The rat model of type 2 diabetes has been used to see what happens if insulin is administered versus sham injections to determine how fast the cohort develop type 2 diabetes. In those animals treated with small injections of insulin, it has been shown that they take as much as twice as long to develop the prevalance of diabetes as the sham treated animals. Also, when they are sacrificed, those receiving the insulin injections have a higher number of viable beta cells in their pancreas. The accepted interpretation is that the injections of insulin take stress off the pancreas and that something about stressing the pancreas makes the beta cells die off faster. Thus serum proinsulin is a useful indicator of pancreatic stress and relief of this stress is observable as reduction in serum proinsulin levels.

Type 2 diabetes is typified by elevated serum levels of proinsulin from early points in the progression of the disease. In addition to signifying pancreatic stress, serum proinsulin can be detrimental in its own right. Serum proinsulin is positively associated with an increased risk of atherosclerotic cardiovascular disease in humans (Haffner et al., Stroke. 29: 1498-1503, 1998; Hanley et al., Diabetes Care 24: 1240-1247, 2001; Zethelius et al., Circulation. 105: 2153, 2002). It is also associated with known atherogenic risk factors such as reduced LDL particle size (Festa et al. Diabetes Care 22: 1688-1693, 1999) and increased plasminogen activator inhibitor type-1 (PAI-1) expression (Schneider et al., Diabetes, 41: 890-895, 1992). Administration of proinsulin to humans in clinical trials in the 1980s resulted in an increased incidence of myocardial infarction and death in subjects receiving the agent. Thus reduction of serum proinsulin levels is an additional therapeutic goal, and one that is not addressed by the current therapies used in the earlier stages of the disease that focus on serum glucose level.

Pulmonary insulin delivered using diketopiperazine microparticles is rapidly absorbed reaching peak serum levels in about 10 to 15 minutes. This is fast enough to mimic the kinetics of the physiologic meal-related first phase insulin response, as evidenced by the shutoff of gluconeogenesis that is observed. Such treatment also leads to reduced levels of serum proinsulin, which is not seen with slower acting insulin preparations. The relative ease of administration via this mode of treatment also facilitates treatment of type 2 diabetes much earlier in the course of the disease than has been traditionally practiced. Thus by using an insulin delivery that mimics first phase kinetics, serum proinsulin levels can be reduced and the literature indicates that this will be accompnaied by similar reductions in atherogenic risk factors. By commencing insulin therapy early in the course of the disease, reduction in pancreatic stress can slow progression of the disease itself.

Some thoughts---was Sanofi CEO Brandicourt not brilliant enough to see the big picture how Afrezza combined with Lantus could have been the big winner? Was he pressured by the board to keep French labor somewhat content (just look up where Sanofi ranks in France in terms of employement). Insider corruption between employees of regulatory agencies and the "money changers"?