Lilly & Inhaled Insulin: Don't Hold Your Breath

Thanks Ed for your artical. Mr.Funtleyder obviously isn't one of the millions who endure multiple injections daily. My hope is Lilly has the fortitude to continue their pursuasion to investors. A "Non Injection Insulin",product will be HUGE. It's not just patients with burn out from multiple injections. As an ageing "on the cusp Baby Boomer", I've been careing for my parents, both Insulin dependent for the past 10 years. Let me assure you CareGivers understand the need for any advancement in the delivery of this medication. Where can I invest!

Clyde--

I assume you will gladly enroll your aging parents in the Phase IV (guinea pig) trial, which is essentially what post-marketing data collection is? You'll also gladly drive them in for their periodic lung-function test to be certain the drug isn't damaging their lungs? Or causing cancer? And if it DOES damage their lungs, you'll support any additional palliative therapy the doctor recommends--all to avoid those nasty needles?

I would certainly recommend that you invest . . . Lilly will get your money from both the investment side and the consumer side . . . a real win-win situation. I'm sure Mr. Taurel will smile all the way to the bank.

Melody-I see you are another crusader, like our resident nutball Lisa Van Syckle. So tell me, which company did you sue?

Bob, Hope you got up on the right side of the bed this morning....Have a nice day!..

Bob--

Actually, I've never sued anyone. Right now, I don't have a "cause of action" since I have found a way to import natural animal insulin from outside the country, and do not have to rely on Lilly's or Novo's 'crap' (E. coli) insulin to survive. I speak so that others may (1) recognize hidden dangers; (2) understand that there are still products available, albeit difficult to obtain; and (3) to shed light on a model set in place when Lilly exploited the system to garner quick approval for rDNA insulin, and then--in tandem with Novo--manipulated the market to remove necessary insulins.

I think I have collected enough evidence, however, that should I be forced to "consume" their rDNA insulin product, with subsequent complications or death resulting, my family would have a cause of action . . . AND supporting evidence. I'm just not ready to sacrifice myself on the altar of pharmagreed.

From your comment, I assume you are heavily invested in pharma . . . and any antagonistic viewpoint threatens your portfolio. As long as the dividends keep coming, and share prices keep rising . . . anything goes? What's the matter--did you suffer a financial setback when Vioxx, Prempro, Actonel, Zyprexa, Avandia (pick one or more) made headlines? Do YOU always see the stupid, noncompliant patient whose only redress is through the judicial system as harmful to your well-being? All these wonderful, safe, efficacious drugs and an army of litigants to affect YOUR bottom line. Boo-Hoo!

I think what Bob was getting at is that without data to back up her claims, Melody's assertions come off as baseless fearmongering.

Near as I can tell from the literature, Lilly's inhaled insulin has a similar effect on glucose parameters as injectable insulin, and no significant long-term changes in pulmonary function tests in patients without baseline lung problems. In fact a search of PubMed of "inhaled insulin AND cancer" turned up exactly 1 result: a letter to the editor in NEJM about cell proliferation in rats receiving Exubera (http://content.nejm.org/cgi/content/full/356/20/2106). But that's about it, and the authors (and other people who understand drug development) note that at this time, you can't say whether there is an association between inhaled insulin and cancer. Obviously, these things may take years to show themselves. Lilly currently has at least 1 active Phase III trial and are recruiting for 8 others.

I've already taken the liberty to check Lilly's clinical trial results page; naturally, they do not have anything because it is still an investigational (i.e., not approved yet) drug, and for obvious IP reasons, neither they nor other pharma companies are required to report data until the drug is approved. However, if there were very serious safety issues (a la torcetripib), we'd hear about it.

Reality--

It is difficult to find relevant scientific studies (in the U.S.), when the baseline comparator (natural animal insulin) was removed from the marketplace. Most trials--whether for transdermal or inhaled (or ingested) insulin--measure ONLY bG-lowering effect of the studied product; and the trial product is measured ONLY against a placebo. Additionally, the trial base is usually defined as "healthy" individuals (or diabetics)--not the base at which the drug will be targeted.

There is a great deal more to diabetes and insulin therapy than merely lowering bloog glucose levels. But as long as this is allowed to be THE metric for efficacy, we will remain entrenched in Pharma's paradigm of "new and better" wonder drugs being promoted because the previous "new and better" wonder drugs did not perform as advertised.

Brent Hoadley, Ph.D., in his "Too Profitable to Cure" and Prof. Dr. med. Arthur Teuscher, in "Insulin: A Voice for Choice" have both provided links to the science that not only question today's treatment protocols, but show the convoluted machinations used to supplant time-proven medicines with 'flash-in-the-pan' wonder drugs.

The fact remains that much of today's "science" is cherrypicked for marketing potential; the patient can be "sold" anything prescribed by his doctor. In the long term, no advertisement on television is going to tell the patient about long term effects such as cancer, emphysema, and COPD that are possibilities for patients using inhaled insulin. Insulin is an anabolic hormone, a metabolic-regulating product that actually could have effects on cell differentiation--e.g., the abnormalities experienced by many diabetics at their injection site.

It appears to me that much of Big Pharma today operates like multi-level marketing schemes: Get in with hoopla and fanfare--get the big bucks--and get out BEFORE the science accumulates to show harm done. Oh, and complain like hell about those patients who somehow survive and seek justice through the legal system.

Reality,

Why do you think Bob brought me into this discusssion?... The Paxil Data backs up my claims of harm and no efficacy!..

And yet,...He calls me a resident nutball...

Melody,

Lilly's product has been tested in both Type I and Type II diabetics, not just healthy patients, and measured it against injectable insulin. They looked at various BG effects, including HBA1c (which some say may be on its way out as a measure of glucose control). I grant you that there is more to DM that just glucose, where else are you going to start to test the efficacy of a drug for diabetes?

However, you're still talking about things like cancer with inhaled insulin, for which there is zero evidence that I could find outside of increased mitosis the rat model with Exubera, and that ain't cancer. Could it turn out to be? Maybe. And the authors acknowledge it's something that needs to be evaluated. I know that insulin growth factor has been associated with various cancers, but a search of meta-analyses for insulin and cancer turned up nothing about injectable insulin -- I would have to look into it further.

I am not familiar with that book. However, I'm sure there were some who thought sulfonylureas were flashes-in-the-pan back in the day. That's not to say that there aren't "me-too" or questionable drugs brought to market these days, but it also doesn't mean that every new drug brought to market is a marketing scam.

I have no idea what potential commercials say, but he studies clearly reported the effects on pulmonary function. You can speculate, but that's all it is -- speculation, and speculation in which you've injected your own preconceived notions.

Sometimes I have to question my own sanity for posting here.

Reality--

The flashes-in-the-pan of which I spoke were NOT the T2 treatments. I refered to:

Humulin--"it's just like the human body makes." NOT

Human Ultralente--"it's just like the (former) gold standard Beef Ultralente, providing true basal insulin." NOT (As a matter of fact, its swift removal from the market SHOULD have been indicative that a bit of false advertising and false claims warranted inspection).

Human NPH--now the only 'basal' product, despite being both peaky, unpredictable and certainly not basal

These products are (or soon will be) off-patent, therefore it becomes okay to question their previous claims, because there are newer, patent-protected, higher-priced products now available--hyped with the same kind of claims we saw previously. Many diabetics are caught in a "Groud Hog Day" scenario from which there is no escape--always a newer drug, a 'tweaked' treatment regimen, more expense . . . but no better outcome (except for drug producers.)

Melody,

You should read up on Exubera, studies just came out proving no greater impact to lung function than a patient on Lantis. The real problem is getting a diabetic to change routine. Once they have therapy that works for them, it's hard to change. Pfizer didn't calculate that into their 1.5 billion a year projections.

Phil--

Who funded the studies? Who designed the studies? Did they prove what Lilly/Pfizer wanted to prove? Were these long-term studies--you know, on the order of the 6-month "major investigative" studies (comprised of about 225 participants) that garnered Lilly its FDA approval of rDNA insulin? Were COIs revealed?

You seem to view diabetics' unwillingness to "switch" as recalcitrance or anti-progress. If you had been forced to switch from one product to another NOT because it performed better, or made your life easier, or improved outcomes, but because the MANUFACTURER had the power to control the market, I think you would view each new "latest, greatest" offering with a very jaundiced eye.

No, I understand their willingness not to switch. I'd be the same way. I like to stick with what works when dealing with a disease as serious as diabetes. The study I speak of was comprised of 8 YEARS worth of data and put to bed the most substantial setback of inhaled insulin, lung functionality.

Also, I haven't read one negative blog/article from an Exubera user. It's actually shown to be extremely effective at controlling A1C numbers, and in several cases was much more effective than its injected counterparts.

I have to ask though, why do you have such a jaded view? Seems like you think pharma is the enemy and is an "Evil Empire".

Last time I checked, most of Americans don't workout, eat like crap and lean on drugs to make up for their poor habits. So who's really the one to blame? Big Pharma for filling a need, or Americans for creating the need?

Phil--

Your last paragraph has a great deal of validity . . . but also opens a much broader opportunity for dialog. We would necessarily have to address issues of societal influence (on both pharma and individuals) that have stymied much finer minds than mine.

Why do I have such a jaded view? Time, age, experience. For every pharma/drug that addresses patient benefit AND profit, you see a multiple working for PROFIT only. Newer drugs hyped that offer no REAL benefit over the ones they replace--except for corporate profitability; drugs that are combined to address issues of "convience"; drugs that treat invented "diseases"; drugs repackaged & renamed to yield much greater prices; and yes, drugs like Exubera, that exploit a very tiny niche (needle-phobics) and then seek to convert the masses . . .all these have engendered my cynicism.

Couple this with a medical profession that is often complicit in pushing "legal" drugs, and an educational system that is heavily influenced by drug manufacturers, I believe it is hard to look at both the industry and the profession with anything less than cynicism.

Phil--

A further thought occurred (after I had posted above) that perhaps most succinctly answers your question: why do you have such a jaded view?

http://www.blacktriangle.org/blog/?p=1654

http://www.annals.org/cgi/content/full/122/6/456

Both of these links specifically address the an issue addressed on Pharmagossip.com today: Those who do not learn from history are doomed to repeat it.

Thanks for the dialog.

Melody, I'd love to have your list of drugs that offer no real benefit over the ones they replace. We know your views on insulin, so lets not include that one.

Melody,

The drugs that come out from other companies that serve the same purpose as the original drug help control pricing through competition.

Now, when Branded drugs go off patent and the company re-formulates to get a new patent, this is crucial to their survival. Generics don't have to do clinicals, don't have to invest millions, if not billions, into R&D. So that means, they don't create anything new, only the name brand guys. I would be more afraid of some generics than of the brand name just because there are certain things they can change (exipients) without conducting new trials or anything. Why, because the FDA allows it. True enough, excipients shouldn't adversely impact the efficacy or safety of a drug, but in some instances they have. So, I don't mind that the branded firms re-formulate and bring out new drugs that treat what a current drug does (if only a little better). They are the ones driving the cures, no one else.

Phil, I agree with the first part of your statement and will add that the 2nd, 3rd, etc. drug in a category may often be more effective than the first or have fewer side effects or may be dosed fewer times per day. All of these are valuable. In addition, the 1st product may not work for the same set of patients that the 2nd or 3rd work for. The heterogeneity of treatment effect is critical. I do disagree with the second part of your statement. For the most part, reformulated products, including pro-drugs, metabolites, L- and R-isomers, often add little or no value. Consider Nexium and Clarinex--not much value over the originals Prilosec and Claritin.

I have been a type 1 diabetic for 49 years. I have taken over 36,000 insulin injections. A small risk from the inhaler is not much a worry for me. Please bring them on...

A majority of patients won't be lining up for inhaled insulin, in large part, because it offers no clinical advantage over injectable insulin, yet sells for as much as 50% more. No private healthcare insurer is going to pay for it, nor will Medicare, unless it does something more or costs less. Dream on if you believe Lilly's version will overcome these issues; the company's market share in insulin in the U.S. market has fallen from a high of from 82% in 2000 to 43% in 2006 according to data from IMS Health, so they no longer call the shots in the U.S. market. As for convincing patients with non insulin dependent diabetes mellitus insulin, their number of treatments continues to increase (including Lilly/Amylin's Byetta, an injectable medicine which is selling briskly), this development is about 20 years too late.