Wednesday, June 23, 2010

Teva Ups Stake in Co. Pursuing Heat Shock Therapy to Stop Autoimmune Diabetes

Last week (June 14, 2010), Israeli drug giant Teva Pharmaceutical Industries Ltd., a company perhaps best known for being the largest manufacturer of generic drugs sold in the U.S., announced that it had exercised an option to raise its ownership stake (to 16%, up from 10% previously) in a company known as Andromeda Biotech (see here and here for more about the latest development). It should be noted that in spite of it's dominace in generics, Teva is not exclusively a generics drug developer/manufacturer, the company also some has its own branded drugs in neurosciences, respiratory and biologics/specialty products, some of which are blockbusters in their own right, even though a majority of it's products (and revenues) are derived from generics.

Although the Teva investment is a general stake in a biotech company, the primary product being developed by Andromeda is a drug that's been in development for well over a decade now (perhaps 15 years or so if I'm not mistaken), known as DiaPep 277®, which is a contraction of the term 'diabetes' and 'peptide' plus some numbers. DiaPep 277 has been treated something like a hot potato over the past decade, as the rights to the drug back in 1997 were then owned by a pharmaceutical company known at the time as Aventis (now Sanofi Aventis), which also makes Lantus and Apidra insulin analogues. At some point (in 2004), Aventis decided that investing more money into DiaPep 277 might be detrimental to it's mega cash-generating insulin business, so they cancelled any further development when the initial contract expired.

A short while after, another Israeli firm named Andromeda Biotech (which has nothing to do with outer space, galaxies, or constellations, but the name is certainly memorable) was formed in 2007 and picked up the rights to the drug, which is a subsidiary of specialized investment firm based in Israel known as Clal (which reportedly means "inclusive" in Hebrew if my sources are correct) Industries and Investments, and it's biotechnology unit (CBI) believed that DiaPep 277 still had sound business potential as a possible autoimmunity treatment for type 1 diabetes and that the science behind it was promising, therefore made some investments (to the tune of somewhere around $10-$15 million) to keep development moving ahead.

A few years ago, the folks at Clal then convinced drug giant Teva to invest in DiaPep 277 (see here for the latest announcement) even though Aventis had dumped it, and in 2009, Teva acquired the worldwide rights to market Diapep 277 if and when it is ever approved. Teva initially made an investment, with options to expand it's ownership stake contingent upon certain development hurdles being met, thus the latest announcement.

What is DiaPep 277? Good question. Here's Some Background.

DiaPep 277 is a synthetic peptide (fragment) consisting of 24 amino acids which are derived from a sequence of the human heat shock protein 60 (Hsp60). This is a protein that's generated naturally by the body when stressed. In 2002, Diabetes In Control had a fairly decent overview written in laymen's terms, and you can view that here. For some additional background, you may also read this brief write-up by immunologist Professior Irun Cohen at the Weizmann Institute of Science, although I didn't find it answered any additional questions about exactly how the treatment works. But Dr. Cohen happens to be a native of Chicago and studied at Johns Hopkins University, so presumably he's pretty knowledgable on the subject matter.

At a very basic level, it is believed that DiaPep 277 somehow modulates the body's immune system (although relatively few details on exactly how it does this have been published, so details are clearly lacking), thus preventing the destruction of pancreatic beta cells that secrete insulin and therefore helps to preserve their natural function. It appears that it may work best in newly-diagnosed patients, but it's much less clear if it has any applicability to longstanding patients. Still, if it works, it could be promising autoimmunity treatment, increasing the number of different options available to doctors and patients.

In many respects, if DiaPep 277 is approved, this treatment would perform a very similar function as MacroGenics' teplizumab or Tolerx's otelixizumab anti-CD3 antibody treatments are supposed to (both of which are now recruiting for their own Phase III human clinical trials): stopping the immune system attack on the pancreatic beta cells, thereby preserving functionality and hopefully setting the stage to restore endogenous insulin production either via some kind of transplant (such as islets), or beta cell regeneration, or some combination thereof. In medical research lingo, this would be described as one component of a "biological cure" for type 1 diabetes, but really two (or more) elements would be required to restore insulin independence.

Where Things Currently Stand With DiaPep 277

DiaPep 277 is now already conducting Phase III human clinical trials at 40 sites in Europe, Israel, and South Africa (but NOT the U.S. or Canada, at least presently, although I believe they've announced recruiting plans for a North American leg of the second part of it's Phase III trials). Based on where things now stand with DiaPep 277's trials, it's fair to say that DiaPep 277 is roughly at the same phase of development as the Macrogenics and Tolerx treatments are, in spite of nearly 15 years of testing and repeated changes in ownership. However, I should point out that for the Phase III trial, a total of 456 newly diagnosed adult and adolescent patients with type 1 diabetes have already successfully been recruited to the study for a treatment period of 2 years (the trial is scheduled to end sometime next year -- in 2011). However, this is not enough trial participants for U.S. or European regulatory approval, thus a second leg of the trial has been added which will presumably increase the number of trial participants needed to ensure the trial results can meet U.S. and European regulatory requirements.

Adromeda Meeting Development Hurdles Means Teva's Investment Will Grow

Apparently, some of the development hurdles Teva had in it's agreement with Andromeda appear to have been met, thus the recent announcement that Teva would increase it's stake in the company, albiet only marginally (an increase of 5%, but for a startup, it's nevertheless a very important and significant source of funding).

Questions on DiaPep's Prospects?

Josh Levy, who writes a blog called "Current Research into a Cure for Type-1 Diabetes" that I follow writes that DiaPep 277 was the earliest possible type 1 cure to go into Phase III human clinical trials (way back in 2005, if I'm not mistaken), and he's always been a bit more pessimistic than I have been about the prospects for this autoimmunity treatment. He argues that the early results were "not very promising, but they added more people to the trial".

Josh and I differ somewhat in how we have interpreted the published trial result information that has been released (at least in the public domain) to date. As I understood it, the reality was that they began the trial with fewer people than regulators in the U.S. and Europe require, but when the results turned out as expected, they then expanded the number enrolled in the trial to meet the U.S. and European approval requirements. There could be any number of reasons why they started with fewer research participants, but one of the most likely is money -- it's far cheaper to start a trial with fewer participants. According to an update I read a while back on Andromeda's website (see here), the following was reported:

"Based on the phase II clinical trials, a phase III clinical trial at 40 sites in Europe, Israel, and South Africa was designed and is currently being conducted.

The study involves 400 patients which includes adults and adolescents for a treatment period of two years.

An interim analysis was performed on 137 patients who completed 12 months of treatment, of which 100 of them completed 18 months of therapy.

An Independent Data Monitoring Committee (IDMC) carefully reviewed the findings from the trial and recommended proceeding with the study as originally designed.

The results showed that no significant drug related adverse events, serious adverse events or lab abnormalities were reported and that there are no safety concerns in continuing the study.

In the study, it was observed that when comparing a population similar to those who participated in the phase II studies, the effect of the drug was similar.

The observed trend of the effect may become more significant once a larger sample size is analyzed.

It was recommended to test a larger number of patients to confirm the effect observed in the current analysis.

In addition, it was recommended to proceed with the study without any change to the design and continue the enrollment of new patients."


Press Releases Written By Non-Native English Speakers Might Skew Understanding

Josh zeroed in on the statement "In the study, it was observed that when comparing a population similar to those who participated in the phase II studies, the effect of the drug was similar" but this does not actually disclose the results of the trial itself. I believe Josh may have assumed that to be the case. He concluded that the results of DiaPep 277 were similar to a placebo, rather than the results being similar to results observed in trial participants in the Phase II trial, which was how I interpreted this statement. I will say that sometimes, when a press release is done by a non-native English speaker (even those whose command of the English language is quite good), some ways of expressing certain elements can be somewhat peculiar and subject to misunderstanding. We have seen how this can occur when a recent BP executive named Carl-Henric Svanberg, whose native language is Swedish, recenly gave a press conference after BP's 4-hour meeting with President Obama at the White House about the massive oil spill into the Gulf of Mexico and clumsily stated that BP cares about "small people" which was widely seen as condescending and rude when his intent may not have been meant that way.

What We Know And Don't Know About DiaPep 277

The simple reality is that not every detail from these drug trials gets published, particularly if those trials have no U.S. arm to them (which has indeed been the case with DiaPep 277, therefore they won't show up on the clinicaltrials.gov website). Josh cited an article from an Israeli newspaper which claimed that "The reason is that the interim result does not provide statistically significant results about the effectiveness of DiaPep 277" which he concluded meant there were not statistically significant results, thus in one of his more recent updates on this treatment, he also claimed that they "changed the way they analyzed the data, and are hoping for good results", but "So far, I have not seen any good news type results from this study, but Andromeda seems very positive, and Teva has put in over [U.S.] $15 million over the last year, so they think that something is there. I just do not see it myself."

That's true, but I don't believe we can draw any solid conclusions based on data we don't see. Frankly, I don't believe Teva would have invested $15 million in something that looked questionable at best, nor would the company increase it's investment, but again, without seeing any specifics, it's quite hard to reach any conclusions. But I can say that the details on the trials have been very hard to come by (Josh Levy doesn't have any referenced on his blog, and I'm not aware of any, either, so aside from those on Andromeda's website, many of which are more than a few years old, the details are few and far between). But, I will say that sometimes studies may appear to show the worst, but when the data is re-examined shows something else, and Andromeda concluded that it was indeed worth proceeding to the next phase of trials.

Re-Examining Data Happens Frequently in Clinical Trials

Consider another recent example of where re-examining trial data turned the results of a trial completely around. As I wrote (see here) in January 2010, Biodel, Inc., which has a new, rapid-acting insulin (and a non-analogue!) called VIAject now pending approval (a decision from the FDA is expected by later this year) in the U.S. and Europe, but a leg of it's Phase III clinical trial in India nearly ended what looks to be the first-ever rapid-acting regular insulin. What happened? The short story is that VIAject trials took place in the U.S., Germany and India. The U.S. and German results were exactly as anticipated, proving the new insulin met the clinical trial results, but this was not the case with the Indian results. After closer examination, the reason was because the blood test results in the Indian trial were tainted by the hot India temperatures. The FDA suggested to the company that they re-examine the data, and when an identifiable subset of blood samples from the Indian trial was excluded from the results, the company found that the Indian trial results were indeed comparable to those in the U.S. and Germany trials. This example shows that re-examining clinical trial results occurs often, and can sometimes can change the outcome from what seems dubious to strongly in the opposite direction. It is not simply about spinning results, but looking at items that may not be apparent to the casual observer, and I don't believe we know enough about DiaPep 277 to draw any conclusions at this time.

Expert Feedback

To get some perspective on the use of this heat shock protein therapy to arrest beta cell destruction, I reached out to some authorities on this subject, some of the immunologists and other experts at the University of Miami Miller School of Medicine's Diabetes Research Institute (DRI).

Several people at the DRI were familiar with DiaPep 277 (in fact, the DRI Executive Director of Medical Development Gary Kleiman said that he was aware of this work/company 15+ years ago), but that they too haven't seen much in the way of solid data on the subject. When I asked if there was any additional data that had been published in the medical or scientific journals on this treatment, Dr. Alberto Pugliese responded by indicating that there was very little he could add since he was not aware of any new published or new unpublished data that might add to the known information. Clearly, the work has been ongoing for some time, but only selected tidbits of information have made it into the public domain. For that reason, we must trust that the research being done is reliable and will satisfy regulatory authorities if and when it is finally submitted for approval. The countdown, however, is on because Teva and Andromeda indicate that the first segment of the Phase III clinical trial will be wrapped up in 2011, and they are presently recruiting for the second Phase III clinical trial. In the interim, watching Teva's moves may be an infrequent but reliable indication as to whether key (and importatnt) milestones are being met, and this latest investment suggests that is indeed happening. We'll just have to stay tuned for more!

Thursday, June 03, 2010

Why Anger Plays A Critical Role In Diabetes Self-Care

The other day, Chris Bishop (Type 1 Tidbits) wrote a very compelling blog post called "Diabetic Superheroes" (see here) which I think was really well said. The simple reality is that anyone who deals with a chronic condition is a superhero, and deserves to be recognized as such, especially since it's such a thank-less job.

A number of people (including many medical professionals) make bold claims that anger should have no role to play in managing a chronic disease like diabetes. Some of these individuals suggest that acceptance is or should be a key component to effective, ongoing self-care. I can't tell you how many diabetes educators who cling to this belief, because over the years, I've met simply too many to even try to recount here.

David Mendosa, whose great work I admire tremendously, recently posted about this very subject, with a story featuring a provocative title "Are You A Noncompliant Diabetic?" (see here). While I agree 100% with David's well-written article about "Incorrect Diabetes Terms" (see here), I still take issue with the contention that getting angry is as unproductive as calling patients noncompliant or diabetic.

David cites a new study in the medical journal Hormones and Behavior, that shows that when people get angry, their heart rates and arterial tension increases along with other psychobiological changes. Those may very well be accurate facts, but I still believe that healthy anger can lead to some very productive outcomes, and for some people, may actually play a vital role in effective self-care.

In fact, healthy anger can mean we have a whole lot more personal power and energy to help solve problems (which is needed on a daily basis to effectively manage a rapidly-morphing disease like type 1 diabetes, where insulin dosages defy the rules at almost every turn). The key is to acknowledge that anger is a healthy and natural emotion, and then learn to channel that emotion and use it in healthy and productive ways.

Personally, I think the minute I "accepted" diabetes into my life was also the same moment that my diabetes management went into the toilet because I viewed it as so permanent. To me, diabetes acceptance = defeat. By accepting diabetes as a permanent part of life, I had little energy or even willingness to stay on top of it, and my health was impacted. When I accepted and welcomed diabetes as a part of who I was, my self-care (and my HbA1c) was much, much worse than it is today. I would argue that anger about the diabetes was a far more effective self-care motivator, and continues to be many years later. In fact, my care did not improve until I completely rejected the idea of accepting and welcoming diabetes into my life. It was only after I channeled my anger and rejection of diabetes into self-care, as well as into fundraising and advocacy, that I achieved better significantly better results. So for those of you who claim that we need to "accept" diabetes, I have always said NO WAY.

Fight against it, diabetes should always be treated as an unwelcome guest in your body and in your family, and it does not belong there! Use that anger for a worthy purpose, instead.

Sure, some CDEs and doctors will point to yet another study of the obvious and ask what evidence I have that anger plays a role in effective self-care. I think my HbA1c's speak for themselves, both before and after my outright rejection of the idea of diabetes acceptance. But for those pin-heads that ask for clinical data to back my assertions up, let me refer you to one of my earliest blog postings, nearly 5 years ago (September 29, 2005) in which I cited a then recent study that showed medical research spending had doubled, yet all of this research had yielded mostly disappointing results. My personal experience proves that anger can indeed play a critical role in diabetes self-management (as it should), so I don't need more validation than that. In fact, we can and should argue that acceptance might actually have the opposite effect on good self-care behavior -- when that anger is channeled properly.

I think one way that "anger" can effectively help deal with diabetes is best demonstrated by the birth of a not-so-little nonprofit organization now known as The Juvenile Diabetes Research Foundation (JDRF), whose very roots were born in anger, not acceptance. That emotion has helped turn millions of frustrated parents and family members into a fundraising and lobbying dynamo (see here for an interesting presentation on the role of advocacy for JDRF), and that organization has arguably done far more to alter the course of diabetes research prioritization than a much longer-established diabetes organization like the American Diabetes Association has. In effect, parents' and patients' anger has been effectively channeled into an organization whose goal is not to maintain the status quo of treating diabetes in perpetuity, but to eradicate this disease completely, and put themselves out of business.

In the words of Lee Ducat, one of JDRF's founders in 1970 and the first President of the organization: "When you have children with an incurable disease, you have an insatiable appetite to do anything and everything you possibly can to help them, and that's why I started this Foundation. I'm optimistic that a cure is going to be found and the Juvenile Diabetes Foundation can go out of business."

Of course, that promise has yet to be fulfilled, but if it weren't for the JDRF, we would be much further away than we are today, and I think the evidence speaks for itself as far as advances are concerned. And anger, I think, played a key role in that. In fact, one could argue that MORE anger about type 2 diabetes could actually go a long way towards changing the research priorities for that form of the disease, possibly advancing cure-related efforts there at a faster pace than we have seen to date. We need look no further than looking at how AIDS activists like Act Up which was the very definition of a patient political advocacy, turned the paradigm on it's head. In 2004, The Wall Street Journal wrote "Not since AIDS advocates stormed scientific meetings in the 80's has a patient group done more to set the agenda of medical research" (in reference to JDRF). That same anger also needs to be unleashed against type 2 diabetes, or I fear we're likely to see just more of the same (which frankly, isn't working very well) for a long time to come.

For me, anger with diabetes is what motivates me to fight so hard against it, and therefore manage this disease as well as humanly possible given the relatively rudimentary tools we have to do the job. But that anger is also what keeps me motivated to continue fighting against it, by fundraising and sharing these views with others. Above all else, I think it's time to finally recognize the tremendous value that anger actually does bring to the equation.

By the way, to catch some of the comments made at my duplicate of this post over at TuDiabetes.org, please visit here!

Wednesday, June 02, 2010

The Business of Diabetes: Is Novo Nordisk's Pullback from Greece Really A Greek Tragedy?

Most Americans likely missed the news from Greece this weekend, but it involved Novo Nordisk, the dominant European supplier of insulin (though certainly not the only one) and the company's decision to stop supplying certain types of insulin (17 products, to be exact) to people in Greece who have type 1 diabetes and require insulin for their very survival. (See here for links to the news stories) The reason: the Danish company refuses to cut prices by 25% which is being demanded by the Greek government.

According to the BBC, Greek citizen and economist Pavlos Panayotacos, whose 10-year-old daughter Nephele has diabetes, wrote to the company expressing concern about the company's move. Novo Nordisk's chairman, Lars Sorensen, wrote back to Mr. Panayotacos shifting responsibility away from his company by stressing that it was "the irresponsible management of finances by the Greek government which puts both you and our company in this difficult position". Not exactly the model of social responsibility Novo Nordisk claims to be in it's corporate brochures!

Novo Nordisk spokesman Mike Rulis also said in an e-mail statement to Reuters a 25% price cut did not allow Novo to run a sustainable business in Greece. Such a cut also would bring prices in Greece "way below what other European countries are paying", Rulis added. Hmmmmmm, this comes after something like 6 consecutive quarters of the company's executives boasting to investors that the company had managed to steadily increase prices (especially in North America, to a somewhat lesser extent elsewhere in the world) on insulin which resulted in higher profit margins on it's insulin products (a smaller percentage can be attributed to greater production efficiencies). One has to wonder how they could have increased their profit margins and still loose money with a 25% price cut, or would it merely revert prices back to where they were in mid-2008, before the global economic slowdown. It's not like inflation has been a huge issue for most of the world (although that could be a problem in the future as long as so many countries, including the U.S. and the U.K., continue to live beyond their fiscal means), so what we're really talking about a hit to Novo's investors, who have grown used to steadily increasing margins and rapid growth from the company while rivals showed much slower growth.

In Defense of Novo Nordisk?

I am certainly the last person to defend any pharmaceutical company, and I believe Novo Nordisk has created a Public Relations disaster for themselves with this action and it's somewhat cold response to these issues, and I have to admit, quite deservedly so. But I DO believe that some comments on this subject have been quite misplaced.

First, Novo Nordisk is not, as some have mistakenly claimed, leaving any Greek type 1 patients to die without access to Novo Nordisk insulin. In fact, Novo Nordisk will continue selling vials of Novolin biosynthetic human insulin (Regular and NPH) in Greece, but the company's more costly pen devices will no longer be sold in Greece, and it's "modern insulins" (Novolog and Levemir) will also be discontinued there, at least temporarily. But before everyone is ready to castrate the Novo Nordisk Apis bull (featured in the company logo, see here for more background on that), let's remember that NO patient requires Novolog or Levemir for survival; these are patent-protected, proprietary molecules, and patients can survive just fine with regular insulin, in much the same way as all patients with diabetes did before these costly new products were introduced in the late 1990's. In fact, a number of meta-analyses conducted have raised some very legitimate questions as to whether these new insulins truly deliver superior glycemic control, because the average HbA1c has barely budged (it has come down, but not by a margin commensurate with the increase in per patient spending on these "modern" insulins) since analogues first appeared.

Novo's Political Stance: We Will Not Be Bullied Into Price Cuts

This really appears to be the company taking a political stance that it will not be bullied into price cuts (the Greek government was demanding across-the-board price cuts of 25%). The company told the Greek government it will not lower the prices of its most recent insulin products, so-called "modern" insulins, and insulin products for use with pen injection systems. As a result wholesalers have stopped ordering these products as they would have to sell them at a loss, Novo claims.

The Greek government's financial woes are well-known, and it has been reported that Greece owes billions of Euros for medicines and equipment purchases made on behalf of state hospitals. Novo Nordisk claims it's owed $36 mm dollars by the Greek state. Greece's National healthcare system is funded by tax revenue, and the Greek Health Service wanted the price of insulin and other drugs to come down because they're broke and heavily in debt. There is some concern that other insulin manufacturers, notably Eli Lilly & Co. which is based in the U.S. and Sanofi Aventis, which is based in France although it's insulin business, which had its origins from Germany's Hoechst AG decades ago, is based in Germany, might follow Novo Nordisk's lead on this issue, this seems unlikely right now. Of note: outside of its core market in Germany and Austria, Sanofi Aventis does not sell biosynthetic human insulin, only insulin analogues, which carry much higher prices anyway.

Competitors' Responses

It seems quite unlikely that competitors will follow Novo Nordisk on this move (at least from my perspective). First, as I commented on one of my fellow d-blogger's postings, back in February 2010, Sanofi Aventis publicly identified diabetes as a "top priority" in pharmaceuticals and even established a global division to help the company achieve its aim of becoming the top firm in diabetes treatments (see here for the text of this story), with a goal of unseating Novo Nordisk for leadership. While Cafe Pharma derided the notion that was likely to happen, most of that came from Novo employees, who conveniently forget that when Novo first entered the U.S. market back in the 1980's as a partner to established U.S. insulin manufacturer ER Squibb & Sons (which would later merge with Bristol Myers), Novo remained an also-ran in the U.S. market for nearly 25 years. It wasn't until the advent of managed care in the U.S. that Novo was able to grow, largely because the company was more experienced than Lilly in dealing with formularies in many European markets.

Lilly, too has lost market share for insulin (today, it's a one-trick pony in the insulin analogue business, with only a rapid-acting analogue available but no long-acting product in its line-up at all), and might see this as an great opportunity to steal market share from it's bitter rival Novo Nordisk. Also, the company recently reorganized and made diabetes a business unit reporting directly to the CEO, so there's more at stake today than there was a few years ago when insulin was in a business unit with other therapeutic areas and was not a primary focus for management at the time. Today, the diabetes unit must show growth, and this is a great way for Lilly and Sanofi to grab share, though I doubt either company will do so if they can't make any money.

There are several other insulin manufacturers in Europe also worth noting here, and none have (thus far) followed Novo's move. One is a U.K. division of a company now owned by an Indian biopharmaceutical and healthcare giant known as Wockhardt, Ltd. Also, Poland has two insulin manufacturers of its own, one being a former state-owned enterprise known as Polfa Tarchomin which first began in 1823, and the other being a much more recent biotech startup known as Bioton, which has grown mainly by expanding into Russia, Ukraine and elsewhere in the former Soviet Union, plus India, Israel and having operations further afield in the Pacific region, notably in Australia, Singapore and China. Bioton, however, has substantial debt, so its growth prospects are likely to be limited until the company can de-leverage itself somewhat. In addition, Merck's Schering-Plough business in the Netherlands is one of the largest contract-manufacturers of insulin (both natural and biosynthetic) on earth, and in fact, is the chosen supplier of biosynthetic human insulin that Connecticut-based Biodel, Inc. has contracted with (I believe that was a 5-year contract signed in early 2009 if I'm not mistaken) once it has regulatory approval for it's VIAject rapid-acting insulin.

The Greek insulin tragedy has already been documented by at least two d-blogging peers, one being an American blogger based in Hong Kong entitled Diabetes 24/7 by Elizabeth Snouffer (see her posts here and here) and the other one being U.K. blog "Put Up or Shoot Up" (see here); naturally I've commented on all of those postings, as you might expect, because I am quite opinionated!

But there are several issues raised by the Novo Nordisk Greek moves. First, if insulin were truly a competitive market, Novo Nordisk's moves would not invoke such fear. But it's not a competitive market by any stretch of the imagination, so today, Novo reportedly controls something like half of the world's insulin market. While the U.S. has not pursued antitrust measures very much over the last 8 years, European regulators have scrutinized monopolistic behavior more closely. Apparently, Novo does not have a monopololy according to European antitrust regulators, but the company's immense worldwide market share has enabled it to influence the market beyond it's market share alone would otherwise suggest. In fact, Novo's dominance in insulin pen design prompted development of both Lilly's Humapen Memoir and Sanofi Aventis' SoloSTAR pens (for both Apidra and Lantus) -- both products have increased competition in the pen device sector. In fact, Novo Nordisk came back with a me-too version of Lilly's Humapen Memoir last fall called the Novopen Echo (see here for the news release).

For the moment, none of the handful of competitors have followed Novo's lead, although traditionally in an oligopoly such as the insulin market, the few competitors have played follow the leader, as I've hinted already, there are signs that Novo's ability to call the shots have slipped in recent years.

What will rivals do in Greece? Will they use Novo's pull-back to grab market share?

Only time will tell. If I had to guess, I would say that Lilly might try to grab some share, since it's really a one-trick pony when it comes to analogues (rapid-acting only, no long-acting analogue) and now that the diabetes business has been made a separate business unit reporting directly to the CEO, there is pressure for management to demonstrate growth that did not exist when insulin fell in with a multi-product, multi disease business model that existed previously. As for Sanofi Aventis, in February, the company identified diabetes as a "top priority" in pharmaceuticals and established a global division to help the company achieve its aim of becoming the top firm in diabetes treatments (see here for the text of this story). True, neither company is going to sell their products at a loss, but this might be the ideal opportunity for these rivals to cash in on Novo's pullback from the Greek market, however small that may be.

In the interim, some have asked whether Novo should bear the cost of Greece's financial mismanagement. Probably not, but Novo (as well as Lilly and Sanofi Aventis) have all aggressively raised prices in a mostly deflationary environment, much to the dismay of healthcare providers worldwide (including nationalized heath insurance plans as well as private healthcare insurance companies in the U.S. and elsewhere). The sad reality is that as long as we allow our markets to be dominated by a small number of companies, patients there will always be a risk of this type of situation happening. Argentina's insulin company, Laboratorios Beta, was born from the Argentine debt crisis and the subsequent lack of affordable insulin in that country. But elsewhere in the world, including Greece and the U.S., have not learned those lessons, and we've allowed greater industry consolidation in the name of economic efficiency. But to avoid continued price increases in a deflationary economic environment, we must have government policies in place that encourage competition in the insulin market, which has simply not been the case for as long as I can recall. But if we had a more dynamic, competitive environment, this type of situation would be much less likely.

As I alluded to in my New Year's posting back in January (see here for details on that), if and when newcomers gain regulatory approval for their new insulin products, I believe Novo's ability to call the shots as the leader will be drastically curtailed (as it loses market share, and they stand to lose the most as the current market share leader), and we can only hope that happens sooner rather than later. As for Novo's "Changing Diabetes" campaign, I cannot help but wonder if this is the kind of change the company had in mind, because frankly, it looks like more of the same, monopolistic behavior we as patients have seen from insulin suppliers for decades!