The $100,000 Diabetes Cure

At a scheduled chat held on Twitter by the Diabetes Social Media Advocacy (DSMA) folks held on Weds., November 3, 2010 (see HERE), one of the topics was related to pharmaceutical companies and social media. There is a great deal of well-deserved skepticism about pharma's über-lusty interest in largely patient-controlled social media space, because right now, they do not engage in much two-way conversation which is at the very heart of what social media is all about (see HERE for more). Presently, pharma is trying to use social media as an advertising channel which does not accept comments, to talk AT patients, not WITH them. Needless to say, this type of communication really does not fly in social media, so most pharma social media efforts have bombed royally. Many claim they do not accept comments to protect adverse reporting which must be directed to the FDA, but many patients suspect that's a cop out because they want the FDA to issue formal guidance that will absolve the industry of any legal liability for what is really little more than common-sense behavior in the social media space. Anyway, in the chat, there were many comments on the theme of how pharma isn't interested in cures, just in selling more product. I commented that I felt the profits in a cure would blow away those earned on selling the next-best-treatment which has pretty much been the diabetes model since the discovery of insulin in 1921.

Conventional wisdom among people with diabetes (PWDs) is that because diabetes is such a huge cash cow for the drug, biotech and medical device companies that this industry (some call it "Dia-Business", the "Diabetes Industry" ... Diabetic Investor David Kliff once even referred to it as the "Diabetes Industrial Complex") that there's no chance of a cure coming from any of these companies who are the biggest financial beneficiaries of keeping patients chronically ill, but never cured. Many just lump all of it together under the collective umbrella of "Big Pharma"), but the idea is that because the industry makes so much money from keeping people with diabetes just well enough to survive, that they are knowingly not pursuing curative therapies. I don't believe this to be true. But before I delve into that, perhaps I should share some relevant historical (that's relative, I'll only go back earlier in the last decade) perspective.

Would You Cure A Profitable Disease?

Back in October 2003, a very popular article by author Dara Mayers entitled "Would You Cure A Profitable Disease?" was published in Diabetes Health magazine (the magazine was still known as "Diabetes Interview" back in those days) explored this topic. The author, Ms. Mayers, tried to be objective, but still suggested that profits were a big dis-incentive to the diabetes industry, thus discouraging at least this segment from actually seeking a cure. She wrote: "Nonetheless, cures for type 1 and type 2 do not seem to be coming from the pharmaceutical industry."

However, that logic is a tad hypocritical (a bit like the pot calling the kettle black), as neither federally-funded researchers, nor researchers funded by non-profits at universities and/or other research centers have managed to find a cure yet, so pharma is in exactly the same boat.

Prospects for drug and biotech companies look very rosy indeed because of demographic growth in the elderly population (which account for about 33% of all drug industry sales anyway, but is expected to grow rapidly as the Baby Boom heads into retirement and their senior years) as well as huge potential for new drugs stemming from discoveries in genomics and biotechnology. There is little doubt that manufacturers have aggressively raised prices to increase their margins, although there is little solid evidence of actual financial benefits to healthcare providers who are footing the bill for their "new and improved" products. That's exactly what has happened with former commody products like insulin. Whether its good or bad is irrelevant; businesses have logically chosen to increase their margins because they have a fiduciary responsibility to do so, and if they can get away with it, why not?

But increasing margins on old products can only work in a non-competitive environment. Pharmaceuticals is already one of the widest-margin U.S. industries, and as long as these companies enjoy monopolies, that can occur. Patent expiration has historically slashed the prices on widely-used medicines.

Now, thanks to The Patient Protection and Affordable Care Act (the so-called healthcare reform legislation sometimes derided by opposition as "Obamacare") which was signed into law by President Obama on March 23, 2010 contains a section called the "Biologics Price Competition and Innovation Act of 2009" (a.k.a. BPCI Act), that's pretty certain to change. That legislation amends the Public Health Service Act, and the Federal Food Drug and Cosmetics Act to create an abbreviated approval pathway for biologic products that are demonstrated to be "highly similar" (biosimilar) to, or "interchangeable" with an FDA-approved biological product. Whether any biologics can EVER be considered "interchangable" remains an unclear, although the FDA has in the past hinted that would not be the case (see HERE).

Regardless, since this is now law, it means the FDA is now obliged by U.S. law to provide guidance for follow-on biopharmaceuticals (generics) inclduing insulin, which has potential to reduce costs significantly, so the era of 10% annual price increases may soon come to an end, especially since the patents on most pricey insulin analogues are due to expire in the next few years (see HERE).

Is Diabetes Too Profitable to Cure?

Aside from fatter profit margins, in the grand scheme of things, when one compares the margins on chronic medicines to those of specialty medicines (think of things like cancer treatments, which are given quite rarely to a relatively small number of patients), the margins are comparatively low on chronic medicines, but much higher on specialty medications like cancer treatments. Thus, if one could transform a disease like diabetes from being a chronic disease to a curable disease, it's safe to presume that a curative medicine(s) would be among the world's biggest blockbusters, making today's blockbusters like Pfizer's Lipitor look pretty miniscule by comparison.

In fact, a diabetes cure (or cures) might possibly be some of the biggest blockbusters the drug and/or biotech industry has ever witnessed. And there is a rapidly growing number of companies whose very business models do not exactly focus on keeping patients chronically ill, but on eradicating their diseases. They haven't succeeded ... yet, but these companies see enormous profits in bringing cures to market.

Finally, the drug industry doesn't hold secret, backroom meetings about how to keep would-be competitors out of their business; they are fiercely competitive with each other, and there are genuine risks that Federal antitrust regulators would step in if they acted in a truly anticompetitive manner, which does serve as a natural control mechanism. It also seems unlikely that any drug company would want to tip off their competitors what they plan or are researching unless it's pretty far along in development and already in the public domain.

To cure type 1 diabetes, the consensus among researchers is that two things need to happen: 1) first, the autoimmune response that caused the disease to occur in the first place must be fixed, creating a state of "self-tolerance" to islets/pancreatic beta cells and 2) second, the functionality of the destroyed islets/pancreatic beta cells must either be replaced with new islets, or restored via regeneration.

There are a variety of companies, many of which are startups, pursuing various parts of this equation. For example, on islet replacement, there are companies who are pursuing xenotransplantation by encapsulating islets from another species (such as pigs, whose insulin is more similar to regular human insulin than some insulin analogues like Novolog, Apidra, Lantus or Levemir based on amino acids and molecular weight). Listed below are a number of companies operating in various spaces in the cure-related therapies (by category).

Islet Replacement Therapies:

Living Cell Technologies (LCT), a publicly-held firm based in New Zealand but listed on the Sydney, Australia stock-exchange.

In addition, others are trying a slightly different route, developing what they are calling Islet Sheet Technologies. Several companies which are not publicly-held firms are pursuing this technology. While it does not appear they are quite as far along as LCT, fellow d-blogger Elizabeth Snouffer did a great piece back in April 2010 about Islet Sheet Technology. Visit her post HERE for more details. Among the firms she writes about are Scott King's (NOT the former editor of Diabetes Health magazine, the OTHER Scott King heading up a firm known as Cerco Medical).

Both involve masking islets to protect the transplanted cells from immune response. The long-term viability is still being researched, but could potentially be replaced without major surgery.

Autoimmunity Treatments:

MacroGenics, Inc. is a publicly-held company based in Rockville, Maryland whose partnership with Eli Lilly & Company, Inc.'s failed to meet it's Phase III trial objectives in October 2010 (see HERE)

Tolerx, Inc. is another firm based in Cambridge, Massachusetts that has a similar, but not identical approach to addressing the autoimmune response that causes type 1 diabetes. Tolerx claims to have a slightly different approach, and was paired with GlaxoSmithKline plc thanks to the JDRF. The company's Phase III human clinical trials are reportedly complete, although the trial results have not yet been released to the public. (Note: in March 2011, Tolerx and GSK ANNOUNCED that otelixizumab had failed to meet its primary efficacy endpoint, although full details will be announced at the American Diabetes Association's Scientific Sessions taking place in June 2011).

Another privately-held firm, DiaKine Therapeutics, Inc. has several products for diabetes in it's development pipeline. On the autoimmunity front is a product known as lisofylline (LSF), which the company describes as a synthetic small molecule with "novel" anti-inflammatory properties that may work in stopping the autoimmune response that causes type 1 diabetes. This is presently in Phase II human clinical trials according to the U.S. Government's ClinicalTrials.gov site, so it has a longer development timeframe than Tolerx's product.

In March 2009, the JDRF announced a partnership on another autoimmunity treatment from Bayhill Therapeutics, Inc. and what was then known as Genentech (now part of Roche). Known by the unglamorous name "BHT-3021" which differs slightly in that it works as an antigen-specific treatment for the insulin molecule itself. However, details on progress have been few and far between on this treatment.

July 2011 Update: Following disappointing results for both the Macrogenics and Tolerx treatments (though the Macrogenics treatment will go back to trials with funding from the National Institutes of Health, suggesting that there may be some evidence that this treatment was not a total failure), in June and July 2011, there were two new autoimmunity partnership deals announced, the first via the JDRF, the second via the Iacocca Foundation. The first one was with a Watertown, Massachusetts-based biotech company named Selecta Biosciences, Inc. for the development of an type 1 diabetes autoimmunity vaccine technology. The other was ANNOUNCED on July 19, 2011 where The Iacocca Family Foundation boosted investment in a Seattle-based biotech firm known as Kineta, Inc. which also has an autoimmunity treatment known by the acronym "ShK-186" in development which is being developed not only for type 1 diabetes, but several other autoimmune diseases as well. For more detail, see the press release HERE.

Islet Regeneration Therapies:

Finally, the companies now pursuing islet regenerative therapies (once dismissed as wishful thinking, but since proven to be not only realistic, but possibly a better alternative to transplantation) are the following different firms:

Transition Therapeutics, Inc., a Toronto (Ontario), Canada-based biotech startup, is a privately-held firm funded by venture capitalists.

Exsulin Corporation based in Burnsville, Minnestota is another privately-held firm that is majority owned by a limited liability corporation (LLC) known as Kinexum, LLC which is based in Harpers Ferry, West Virgina (in the Washington, DC exurbs).

CureDM, Inc., based in Wilmington, Delaware developing a product they call Pancreate™ (proisletide acetate). In April 2010, the firm signed a commercialization agreement with Franco-German global pharmaceutical giant Sanofi Aventis S.A. best known as the maker of Lantus and Apidra insulin analogues.

So Where Are the Cures?

All of this begs the question: where are the cures, then?

This year, one of my favorite medical writers, Sharon Begley, who writes for Newsweek magazine, but previously wrote for such well-known newspapers as The Washington Post and The Wall Street Journal, looked directly at this question.

In the May 15, 2010 issue of Newsweek, the cover story was hers and entitled, appropriately enough "Desperately Seeking Cures", probing into why the road from promising scientific breakthroughs to real-world remedies has become all but a dead-end (those are her words, not mine!).

In fact, she even cited stats from the FDA, stating that from 1996 to 1999, the U.S. Food and Drug Administration approved 157 new drugs. In the comparable period a decade later—that is, from 2006 to 2009—the agency approved 74. Not among them were any cures, or even meaningfully effective treatments, for Alzheimer's disease, lung or pancreatic cancer, Parkinson's disease, Huntington's disease, diabetes or a host of other afflictions that destroy lives.

Her story found several culprits, most notable was the fact that the nation's biomedical funding and training system are set up to do one thing, and she notes that they do that superlatively: make discoveries. Back in 2008, Ms. Begley wrote another story with a similar title, although less in-depth "Where Are the Cures?".

In that article, she wrote "Discoveries is what scientists dream of, that is what gets them published in leading journals (the coin of the realm in academia) and that is what gets them grants from the National Institutes of Health. She added that the less glamorous work of testing potential treatments in actual patients -- the grunt work, as she referred to it, that turns a breakthrough into something that can actually be tried in patients is seldom on their academic agenda. That responsibility falls elsewhere, and helps explain why so much money is spent yet few cures ever seem to emerge from the billions we spend.

Patent Problems

Another factor: the nation's patent system, which tends to reject applications that are already published in scientific and medical journals that helps researchers advance their own careers, and without patent protection, hardly any drug or biotech company would be interested.

Then there is a not-so-little matter of licensing discoveries from NIH-funded research; sometimes startup firms see potential in these discoveries, but cannot afford big upfront payments that a big drug company like Pfizer or Lilly could afford, and the NIH has been asking as if all companies had Pfizer's pockets.

"NIH has no skin in the game, so they have no inducement to work with a company" to get a discovery from the lab to patients, says Eric Gulve, president of BioGenerator, a nonprofit in St. Louis that advises and provides seed money for biotech startups. "There isn't a sense of urgency." A top lab chief at the NIH laments that when scientists like himself push the licensing office to move a discovery toward commercialization, "it's just another piece of paper to them." Without the license, the startup struggles to stay alive.

The Role of Nonprofits

Of course, Ms. Begley did mention how an increasing numbers of nonprofit organizations are trying to fund the next steps in "translational research". Among them is a big one in type 1 diabetes research: the Juvenile Diabetes Research Foundation (JDRF). Increasingly, nonprofits like JDRF are stepping in to fund the research needed to take promising concepts from discovery to commercialization, filling a badly-needed void.

In fact, Ms. Begley wrote an entire article on that very subject back when she was still writing for The Wall Street Journal back in 2007 entitled "Why Nonprofits Fund For-Profit Companies Doing Drug Research" in which the JDRF along with others like the Michael J. Fox Foundation for Parkinson's Research, and the Myelin Repair Foundation (for multiple sclerosis) who have all veered away from the NIH model of "here's some money; go discover something."

Instead, these organizations are managing and directing scientists more closely, requiring them to share data before it is published, cooperate, and do the nonsexy development work required after a discovery is made. But it isn't always popular to do so. In the 2007 Wall Street Journal article stated clearly acknowledged that:

"Charities realize that writing checks to for-profits might not be what their donors had in mind. 'We debated whether it was right for our money to go to a company that might make a profit,' says JDRF board member Michael White. 'We're not unconcerned about that. But we've invested so much in discovery, what we need now is to take these things to market. We're taking on the role of 'venture philanthropists.'"

And not all of these investments will even pay off; for a very relavant example, as already noted, on October 20, 2010, MacroGenics, Inc. and it's big pharma partner, Eli Lilly and Company announced that a potential autoimmunity treatment called teplizumab, whose Phase III human clinical trial called Protégé, did NOT meet the primary efficacy endpoint of the study, which was a composite of a patient's total daily insulin usage and HbA1c level at 12 months (see HERE for more detail). A similar treatment from a startup called Tolerx and it's big pharma partner (thanks to the JDRF's involvement) GlaxoSmithKline remains upbeat about their own treatment, called otelixizumab, is wrapping up analysis of it's own Phase III human clinical trial called DEFEND.

One key unresolved pitfall Sharon Begley wrote about: "blockbuster-itis" in the drug industry, but it appears that experience may have taught non-profits how to prevent pharma "blockbuster-itis" from killing the goose that lays the golden cure egg.

Egg on the JDRF's Face?

Occasionally, the big pharma company will do something that really p!$$es their nonprofit "partner" off in their relentless drive for fat profits. In one JDRF program for islet regeneration efforts, the Toronto-based biotech startup known as Transition Therapeutics, which JDRF partnered with Eli Lilly & Company, did see fairly solid evidence of efficacy of it's gastrin-based therapies in patients with both type 1 diabetes as well as type 2 diabetes.

But then big-pharma partner Eli Lilly & Company decided to push clinical trials towards type 2 diabetes and cancelling the type 1 trials, theorizing that it could potentially sell the product to far more type 2's than patients with type 1, thus increasing the company's bottom line faster. The company likely assumed if is eventually approved for that indication, then they could then move to "extend" the drug's label approval to type 1 patients, albeit that could take many years more, which was not quite what the JDRF had in mind when pairing these organizations together. In fact, JDRF had invested fundraiser dollars in the program only to see clinical trials in type 1 patients cancelled by a greedy pharma partner.

Social Media Pushes for Greater Transparency

Of course, things were easier before patient-bloggers hit the scene. For example, last autumn (2009), fellow diabetes blogger Joshua Levy and I speculated on what Lilly's move meant as trial results for Transition Therapeutics treatment known as TT-223 and the fact that they pulled the plug on the type 1 trial. I actually wrote about it in my mid-year progress report. Bill Ahearn is the Vice President, Strategic Communications for JDRF International went so far as to contact Joshua Levy in the comments on his blog about the Transition Therapeutics approach, while I received an e-mail from another JDRF staffer with very similar comments. Had this occurred a decade ago, the organization might have controlled the dialog either by ignoring it and allowing it to pass, or with carefully-scripted press releases. But it became a public relations disaster for the organization, and patient bloggers effectively forced the JDRF to confront it head-on, as these things had gone viral, hence the response.

To be sure, there is no prior, proven pathway for "venture philanthropists" as JDRF called themselves (in Ms. Begley's 2007 Wall Street Journal article), so one can call this a training exercise for JDRF's Industry Discovery and Development Partnerships (IDDP) program. No doubt, the JDRF was embarrassed by Lilly's move and had to do damage control as a result. But this move demonstrates the power that the social media space (including patient bloggers) has had on even nonprofit organizations. Although the investment was reportedly relatively small and Lilly's interest in the treatment (especially now that the company faces a "patent cliff") could bring it to market, where it could then be researched "off-label" in the type 1 universe, thereby saving Lilly millions. If it does not gain approval for type 2 diabetes, that does not necessarily mean the drug would be dead, either (although Lilly might loose interest by then) forcing the JDRF to find a new pharmaceutical partner.

One thing is certain: JDRF probably learned it's lesson from this experience. In recent IDDP announcements, virtually all require the partners to meet key milestones before the organization pays any more. This may prevent another of the TT-223 fiasco from occurring on the organization's dime in the future.

Be Prepared to Mortgage Your House for a Cure

In 2008, diabetes writer David Mendosa INTERVIEWED Zoe Heinenman Myers, the vice president of marketing for the company now known as Exsulin (it was known as Kinexum Metabolics at that time), and then at length with Lisa Jansa, the company's new CEO about where this interesting treatment stood. David asked numerous questions that would be of interest to patients with diabetes. But the element that really stood out in my mind was the following quote, which was taken from PAGE 3 of the story:

"Something as big as INGAP won't come cheap. 'We don't anticipate that it will exceed $20,000 for a single course of treatment,' Lisa [Jansa, CEO of Exsulin] told me. Later, however, she is confident that as they scale up production they will be able to bring the cost down."

Exsulin also told David Mendosa that the company was not certain if periodic re-treatments might be required, something that current clinical trials may answer. Perhaps with an effective autoimmunity treatment, that need would be eliminated. Right now, we simply do not know the answers to these questions. This is why the term "remission" has become favored by the medical profession over using the term "cure". As former New York Yankees player and manager Yogi Berra once famously said "It ain't over till it's over." But regenerating islets solves only half the type 1 diabetes puzzle; the autoimmunity issue must also be solved, so its possible that the cost of a cure could easily be in the $100,000 range, including any periodically necessary re-treatments for either (or both) components.

All of this makes me wonder: will we see an asset-backed securities market emerge for diabetes cures (maybe as "Cure-Backed Securities?"), and how much will for-profit insurance companies be willing to pay for? What if that market works anything like Fannie Mae and Freddie Mac?

It seems clear that the margins on any curative therapies are destined to become blockbusters, which means the drug industry's own desire for billion-dollar products may push even more of them into the high-margin cure therapies, rather simply more than new-and-improved versions of lower-margin century-old products, and follow-on biologics will undoubtedly help. We have already seen Lilly, Sanofi Aventis and others partner with startups in curative therapies. It appears that non-profits like the JDRF's experience with Lilly and Transition Therapeutics means the days of writing checks without milestones being met required of pharma partners are permanently over, and not a moment too soon!

Flaws Revealed in "Non-Adherence" Models

On October 19, 2010, Amy Tenderich of DiabetesMine wrote a post asking whether "'Adherence' Is the New 'Compliance'?". Although the medical profession has worked hard to abandon the attitude of "blaming the patient" (they aren't 100% there - yet - but no one can deny the effort), decades of this attitude has been transferred to such parties as healthcare providers (e.g. insurance companies who pay the bills) and other HIPAA "covered-entities" like pharmacy benefits managers who hope to use this privileged data to make even more money.


Various statistical models are now being marketed by various PBMs and data-mining firms who are selling the sales data back to insurance companies to squeal on so-called "non-adherent" patients, hopefully to help improve medication compliance, which they theorize will save money. In August 2010, for example, CVS/Caremark's Behavioral Change Research Partnership was launched (see HERE) to study how behavioral economics — the science behind the idea of using "nudges" to help consumers improve their decisions – could be applied to health-care behavior, specifically prescription drug choices (meaning whether or not to fill orders). More recently, rival Express Scripts introduced (see HERE) a software system that determines which of its enrollees are most likely to stop using their medications in the middle of a prescribed regimen, with particular focus on diabetes, hypertension and high cholesterol patients. Medco most likely has a similar program, although that company has certainly been quieter about it.

On November 10, 2010, The Wall Street Journal Health Blog featured another post (see HERE) highlighting an interesting hole in this statistical data-mining, and the pharmacies such as CVS and Walgreens who may be playing a role in these flawed assumptions in their models. Low-cost generics programs pioneered by Wal-Mart and Target, but since adopted by most pharmacy retailers, may actually be responsible for polluting the very data they think they know about patients because most pharmacies never bother to submit insurance claims for low-cost generics. The patient/consumer doesn't really care as long as their drugs are inexpensive, but the healthcare plan and the data-mining companies look at this as non-adherence. Good statisticians can factor these data issues things into their models by giving these factors less weight, but right now, it seems the patient annoyance factor may be due to rise based on mis-information from data-mining companies, with no effort to address these issues.

If you are accused by your insurance company of being non-adherent for a medicine that sells as a low-cost generic, you should tell them you got the medicine for $4 and their models probably do not consider the fact that the pharmacies don't submit a claim for those sales, therefore they may be entitled to a refund from the PBM and/or data-mining company that sold them the costly model, but that they can stop harassing you for factually-inaccurate non-adherence.

WDD and November as NDM

Today is World Diabetes Day (WDD), this day was chosen because it's the birthday of one of the discovers of the hormone insulin, Frederick Banting. One unique element about WDD is that this day became an official United Nations Day in 2007 with the passage of United Nation (UN) Resolution 61/225, and this is quite unique because it's the first-ever day UN day marking a non-communicable disease. This is supposed to help raise awareness about diabetes on a worldwide basis, although the reality is that this day is really more for the segment of the population who do NOT have diabetes (or people whose family lives have not been impacted by the disease), as persons with diabetes (PWDs) and their families already have 365 days with diabetes every year (366 days in leap years) so few need any public service announcements to remind them about it.


Personally, I have mixed feelings about this day.

First, the media coverage is inconsistent and frequently misleading and too often inaccurate. Also, does designating a day to these diseases give the world the rest of the year to forget about diabetes, continue their collective ignorance about the disease the rest of the year? Finally, the notion of diabetes education and prevention, which is the theme from the years 2009 until 2013, is kind of lost on me. Nothing I could have done would have prevented me from getting autoimmune-mediated type 1 diabetes, and I already know far more than I want to about diabetes.

I never volunteered to educate the world's ignorant masses by correcting inaccuracies in news stories printed in the media, on television or on the radio, and frankly, I shouldn't have to. The mere fact that I should have to do this is indicative of a collective failure that the day's goals have yet to be met (at least to some degree, anyway).

Having complained about the shortcomings of WDD, I do believe in the effort behind it and what it has potential to do. The American Diabetes Association did a minor press release, but could have done so much more. This topic came up in the Roche Social Media Summit this summer, and I think the ADA was more than a little embarrassed at not putting more effort behind WDD. As it stands, this year, The Empire State Building was lit up this year in blue and white NOT thanks to efforts from the ADA, but to efforts by the Juvenile Diabetes Research Foundation (JDRF).

Still, I think getting more information in front of many people is helpful, and although there's not yet a damn thing the ADA or anyone else can do to prevent type 1 diabetes (and they have done little to help fund research that companies like Diamyd that is actually pursuing a vaccine for type 1 diabetes that also has potential to actually prevent type 1 from occurring (see HERE for my interview with this company), the issue of prevention is still important when it comes to diabetes as a whole. Time will tell what the cost will be to vaccinate kids for type 1, and I wonder whether all the brew ha-ha about vaccinations and autism thanks to celebrities like Jenny McCarthy might make these efforts unnecessarily challenging.

The Diabetes Hands Foundation (best known for operating the online community TuDiabetes.org) sponsored the Big Blue Test, and although the video effort met the number of views to guarantee funds matching from Roche to help InsulinforLife.org, you should still check that out HERE.

Beyond that stuff, however, I'd like to mention another effort that is continuing throughout the month of November called "BePartoftheCURE.org" (for more background, see HERE). The following is a video summary of this campaign:



You can catch one of my photos at the top, right-hand part of the letter "C" on the BePartoftheCURE.org mosaic of photos, although my plans are to upload others, and I would encourage my readers to do so, too! The DRI has a singular focus on a cure, and I believe their collaborative, open approach (rather than keeping promising discoveries to themselves) is the right approach towards finding a cure. If only other diabetes organizations did the same thing!

Hopefully, your World Diabetes Day was spent sharing positive stories about progress on diabetes research, rather than defending if you can eat something. Just remember, President Obama declared November 2010 to be National Diabetes Month (NDM) -- you can catch my earlier post HERE, and there's still time to participate in all of these events!

11/9: D-Blog Day & 6 Things You SHOULD know About Diabetes

In honor of WDD and Today is DBlog Day ... a tradition Gina Capone started back on November 9, 2005 during Diabetes Awareness Month to help unite diabetes bloggers and create more awareness about diabetes. Also, check out my recent post at "Most Americans Don't Know $#!t About Diabetes" for more cynicism!




This year's topic is: 6 things you want people to know about diabetes.

I have participated in some, but not all of these events in the past. It's your lucky month, folks, because I'm stealing much of my content from Scott Strange at "Strangely Diabetic". He's got 6 more years of life with diabetes than me (I've had 34 years as of 2010), but I added a few that were relevant to me. Guess which ones are mine!

1. Diabetes is not a death sentence, it is however a life sentence that requires constant dedication and attention. If I don't take care of it, "it" will "take care" of me.

2. Although there are better things to have, few are worse than diabetes. I have no fear of hell, after all, I've lived a lifetime with diabetes! The only great thing ever to come from this f'ing disease: the diabetes online community (the D-OC)! Thanks to all of my fellow members ... you guys and gals are AWESOME!

3. Managing diabetes is more art than science. Anyone who tells you otherwise has been studying the Complete Bullshit Guide to Diabetes Management 101, and obviously has no personal experience actually living with diabetes themselves.

4. The DCCT was not so much a landmark study, but a sentence to doubling the work required of the patient, as well as the cost passed on to the patient, without so much as a guarantee of a life without complications. Remind me WTF it did for me again?

5. Biosynthetic insulin analogues have done absolutely nothing to improve my glycemic control; I'd happily trade Levemir for porcine Lente any day, and I had a comparable HbA1c back then, too, plus life was easier and cheaper. But analogues have quadrupled the amount of money that I have to pay for insulin ... for life. Thanks for the advance!

6. I have Type 1 diabetes and no matter how much I exercise and how well I diet, I will be dead by tomorrow without an external supply of insulin.

What, only six?! Geez, that was quick!

Most Americans Don't Know $#!t About Diabetes

With a title like this, I hope to attract some readership out of sheer curiosity!

Let's begin by noting that November 14, 2010 is World Diabetes Day. This is the first-ever day designated by the United Nations and World Health Organization for non-communicable diseases. President Obama has issued a proclamation declaring November 2010 to be National Diabetes Month. No doubt, there will be a lot of press about diabetes in the coming days, and much of the coverage will focus on how much of a drain on limited healthcare dollars these diseases are or how horrible the consequences of diabetes can be. Unfortunately, much of this will be bad reporting, which conveniently omits key facts to fit a story in someplace.

Let's begin with the basics: most of what the average person THINKS they know about diabetes is just plain wrong -- that's a sad but true fact. You may note that in the paragraph preceding this one, I used the plural term "diseases" to describe diabetes. That's because diabetes, contrary to popular belief, is not a single disease, and no one fact applies to every person living with diabetes.

Facts back this assertion up. Back in 2007, medical device manufacturer Medtronic commissioned a survey (see HERE for more) conducted by Harris Interactive of 2,436 American adults which found that 80% of the American public could not even distinguish between type 1 and type 2 diabetes. Even more troubling was the finding that nearly 70% (67% to be exact) of those who responded to the poll incorrectly believed there was already a cure for type 1 diabetes (there isn't). Other troubling findings were as follows:

While more than half 51% knew there were two types of diabetes, more than a third (36%) also believed there was either a "type 3 or 4" diabetes (there aren't). This is indicative of just how little knowledge most Americans really have about diabetes.

One-third (32%) believed exercise could be a "cure" and one-fourth (25%) believed that proper diet could "cure" the disease. Neither is a true.

True, diabetes does have something to do with blood glucose levels (sometimes mistakenly referred to as blood sugars, including by many doctors who try to use terms that are easy to understand), but the disease rarely has anything to do with with cane sugar. Intrigued? Good -- please keep reading!

The fact is that most foods humans eat are eventually metabolized into a basic fuel used by the cells called glucose, but those aren't nececessarily sweets. Even proteins like meats will eventually be converted into glucose because that's the only fuel that cells can use. So the next time you're trying to feign concern by giving a person with diabetes some God-awful "sugar-free" stuff, realize that those things aren't necessarily any better (or worse) than the real thing may be, especially since that stuff also may cut the sugar, but many load up on fat, salt and other dietary taboos in place of sugar.

When blood glucose levels stay high consistently, that's indicative of diabetes. But even people who do not have diabetes will have "high" blood glucose levels immediately after eating, especially if they've eaten a highly-processed food that's loaded with carbohydrates.

But beyond this, there are far too many misperceptions about diabetes.

One is that diabetes is related to obesity. The fact is that many people with diabetes are normal weight or thin, and people diagnosed with type 1 diabetes usually loose a lot of weight prior to being diagnosed. Type 1 diabetes is an autoimmune disease where the body's immune system makes a mistake and attacks and destroys the cells that produce a hormone called insulin which exists in all human beings (except those with type 1 and some with type 2 diabetes). No amount of diet alteration or exercise will prevent type 1 diabetes from occurring. This is a fact that many editors are quick to omit to save space.

Also, contrary to what most articles routinely report, obesity does not CAUSE cause type 2 diabetes, but obesity IS actually one way the body protects the body from the ill-effects of type 2 diabetes. True, people who are overweight can sometimes prevent themselves from ever developing type 2 diabetes by losing weight, but realize that the diabetes happens first, not the weight gain, and the disease makes it much more difficult to loose the extra pounds, plus many medications to treat diabetes often make weight-loss even more difficult.

Finally, well-managed diabetes almost never causes blindness, kidney failure or heart disease. Only poorly managed diabetes (either type) causes these things, but managing diabetes is an incredibly complex task that requires a lifetime of commitment. It CAN be done, and people who do so often lead fulfulling lives, but doing so is no small task and should not be treated so casually. It's a marathon, not a sprint.

Now that I've teased you with the real facts, I hope you will decide to learn more about what is arguably a complex group of diseaseS. The reality is that diabetes is incredibly complex that most doctors spend many years, and a short article is usually not enough information. The average person cannot possibly know all there is to know, and you aren't expected to.

But ... you are also expected not to start blabbering like you do know something about the disease when you really do not. When you don't know something, it's always better to ask questions rather than blurting out unsolicited advice proving how stupid you are about the subject -- that's just plain rude. To help you out with this, the Behavioral Diabetes Institute has created some handy etiquette cards for people who do NOT have diabetes. Download one for yourself HERE and read it before saying something stupid.

The Business of Diabetes: Biodel's Linjeta Is Delayed

As I WROTE previously, October 30, 2010 was the FDA's legally-mandated date to respond to Biodel, Inc.'s new drug application for Linjeta (formerly known as VIAject), which is a new, rapid-acting insulin formulation. Of course, the FDA is closed on Saturday, so the agency could have responded on Friday or waited until Monday, November 1, 2010 (the FDA chose the latter). The news was that the FDA could not approve Linjeta without at least a 2 small additional clinical trials to make up for the compromised samples which Biodel excluded from the India type 1 sample. The FDA also asked for some additional data on stability and manufacturing, although Biodel seems very confident they can adequately address those questions without delay.

Linjeta is a very interesting product because it's actually faster than an insulin analogue, yet is regular human insulin that whose genetic structure is unchanged, but the absortion profile is expedited by the addition of a few generally recognized as safe ingredients. First, they remove zinc using ethylenediaminetetraacetic acid (usually abbreviated as "EDTA") which destabilizes the hexamer of the insulin molecule; then, by adding citric acid (found naturally in citrus fruits like lemons and oranges, which you may recognize as a food ingredient that acts as natural preservative and also adds an acidic, or sour, taste to foods and soft drinks), which masks the surface charges and further destabilizes the insulin molecule so that it does not form hexamers as it would normally when injected into the skin without these modifications. On this topic, the company told investors:

"The presence of EDTA and citric acid dissociates the naturally occurring insulin hexamer and neutralizes the charges on the surface of the molecule. This enables a more rapid shift to a monomeric form upon injection compared to RHI (regular human insulin), lispro (e.g. Humalog) and aspart (e.g. Novolog/Novorapid)."


This makes humble old regular insulin, which incidentally is the ONLY kind found in the bodies of patients who do NOT have diabetes, work faster than completely man-made insulin-like molecules more popularly referred to as "insulin analogues" which do not exist anywhere in nature.

Aside from a fundamentally unique way of expediting insulin absorption into the bloodstream, the company has patented this technology and plans to apply it to a number of other medicines as well (it could also be applied to existing rapid-acting analogues to make them even faster). But the company's diabetes pipeline is not just limited to rapid-acting insulin, it also includes modifications to glucagon which is highly unstable as a liquid and therefore requires a cumbersome reconsitution process, as well as modifications to long-acting insulin formulations such as Lantus to enable these to be extended over a longer period of time, or shortened (not everyone wants or requires 24 hours of basal coverage), and even an oral insulin formulation aimed squarely at the insulin-naïve type 2 population. The basic strategy is to modify already FDA-approved drugs using patent-protected technology which hopefully brings them to market faster than would be possible a completely brand-new drug would.

The investment community has been down on the company's sell-it-ourselves (sort-of) strategy, and seems to have preferred that the company licensed the technology to third-parties instead. However, while biotechnology-manufactured insulin was leading-edge technology back in 1982, it's pretty rudimentary stuff nowadays enabling startups to rely on contract manufacturers for most of it, making capital expenditure relatively small.

Specifics on the FDA's CRL (complete response letter) on Linjeta

The FDA's so-called CRL (complete response letter) basically said that the FDA's review cycle for Linjeta was complete and that the application could not be approved in its present form without some additional clinical trials. The stock market punished Biodel's (BIOD) stock on the news, causing Biodel's shares to plunge by more than half, even though the company had stated all along that it never planned to begin marketing Linjeta until 2011 anyway. The real question now is how soon that can happen?

In essence, the clinical trials on the type 1 population were the main reason for the decision. Just some fast, relevant background: blood samples taken from some of the participants in the India type 1 trial were compromised by excessive heat before arriving at the laboratories. That constituted one leg of the trial, but studies undertaken on type 1s in the U.S. and Germany demonstrated very clear noniferiority to existing insulin therapies. The company decided to pursue it's application excluding the very small subset of the Indian leg of the type 1 trial whose blood samples were compromised following conversations with the FDA during the summer of 2009. But in it's CRL, FDA regulators determined that Biodel's decision to exclude Indian trial data for the Type 1 study "was post-hoc and therefore not sufficient for establishing conclusive evidence of efficacy," according to the company's news release. Meanwhile, "In the Type 2 trial analysis, the FDA acknowledged that non-inferiority was established in the completer population but stated that non-inferiority was not established in the intent-to-treat population because the agency did not consider a post-hoc modification of the statistical model as establishing conclusive evidence of efficacy." In other words, non-inferiority was proven on the type 2 population, but because the company had problems with the type 1 population samples and modified the statistical analysis as a result, that was a modification that rendered the FDA unable to effectively evaluate the results. The newly, more-cautious FDA said that wasn't enough to get an approval, anxious to avoid yet another meltdown as seen with various other drugs that were approved in more lenient times only to face a recall later.

At a conference call for investors today, Biodel was reluctant to speculate on exactly what will be required for the new trials. For example, it might be possible to conduct another trial of type 1s using Linjeta and combine the data with the already-conducted trials in the U.S. and Germany, but until the company meets with the reviewers at the FDA, they were unwilling to speculate on the size or cost of the new trials, or provide an estimated time of arrival for any of this until after they meet with the Food and Drug Administration to discuss the issues outlined in the CRL itself.

The FDA's CRL also had some questions on Biodel's modifications to the insulin itself. If I recall correctly, in the clinical trials, patients used U-25 insulin (as opposed to the market standard of U-100 insulin) even though the company's plan was always to sell U-100 insulin, not a lower concentration. For this reason, the FDA asked for some additional information. The FDA also requested some additional data related to stability and manufacturing. Specifically, Biodel was purchasing apoules (e.g. insulin vials) from a contract manufacturer known as Hyaluron Inc. which is pre-filled syringe maker that was acquired by a company known as Albany Molecular Research Inc. earlier this year. The FDA warned Albany Molecular Research/Hyaluron of possible violations at its manufacturing facility, which Albany Molecular actually acquired as part of its purchase of Hyaluron Inc. back in June 2010.

The FDA also asked about another contract manufacturer for Linjeta, in this case, Wockhardt Ltd., which Biodel has chosen to be it's supplier of insulin pen devices. In October 2009, Biodel executed a letter of intent with the FDA to purchase a disposable insulin pen designed by Wockhardt Ltd. for use with Linjeta. Wockhardt’s UK manufacturing facility would fill 3ml cartridges and assemble disposable pens based on a pen design based on an existing Wockhardt insulin pen already being marketed in India. The company intended to submit that pen to the FDA for review in either late 2010 or early 2011 after completing certain modifications that the company believed would improve the pen's commercial performance, although the company did not specify what those modifications might be, there was suspicion that dosage in 0.5 unit increments might be on the drawing board, making it more salable to the insulin-sensitive type 1 audience that comprises an overwhelming majority of the insulin using-population (even though the type 2 audience uses more insulin by volume). Although the insulin pen issue was not directly related to whether or not regulators could approve Linjeta itself, the company told investors all along that even if Linjeta was approved by the FDA prior to the FDA approving the disposable pen, the company did not intend to commercially launch Linjeta until a disposable pen version of the product was approved. The company was extremely confident that it could sufficiently address the concerns about it's suppliers (namely Albany Molecular Research/Hyaluron and Wockhardt Ltd.).

This in many respects is the classic tale of a biotech startup that relies so heavily on third-party contract manufacturers. If one component of the supply chain has issues, it can affect the startup's product, too. The company was unable to assuage all investor concerns during it's November 1, 2010 conference call, but is very likely to provide a much more detailed update following it's meeting with the FDA.

Biodel, Inc. As Acquisition Bait for Eli Lilly & Co. or Sanofi-Aventis?

In the interim, even though Biodel's finances are quite sound for a biotech startup, there is already speculation that Biodel could well be sold to an established pharmaceutical company. Two names on the top of those speculators' lists: Eli Lilly & Co. or Sanofi-Aventis. While both of these companies already hold a dominant postition in the global insulin market, Lilly's insulin business continues to lose market share to Novo Nordisk (and to a slightly lesser extent Sanofi-Aventis), routinely being dropped to second-tier status from many insurance company formularies or being dropped altogether. What's more, the patent for Humalog (insulin lispro rDNA origin) expires about a year from now, and the prospect for generics has never been greater now that U.S. law is forcing the FDA to outline approval procedures for follow-on biopharmaceuticals. A meeting will be held at the FDA this month to discuss this issue further and resolve some outstanding concerns.

Lilly has no long-acting analogue to compete with Sanofi-Aventis' blockbuster Lantus (insulin glargine rDNA origin), which is the world's best-selling insulin variety representing $4.0 billion in sales each year, or Novo Nordisk's Levemir (insulin detemir rDNA origin), putting the company at a competitive disadvantage when insurers choose preferred insulin brands. For Sanofi-Aventis, Biodel has some technology that could not only make it's Apidra (insulin glulisine rDNA origin) work even faster (even though the patents for Apidra don't expire for a few more years), but also make it's mega-blockbuster Lantus (whose patent expires in 2014) work better by extending the profile (longer and "peakless") and/or adjustable, thus enabling a possible patent extension for a modified version of Lantus to potentially be sold down the road assuming it gains regulatory approval.

Why would either company want to buy Biodel when the company is basically re-tooling their existing products?

Simple, as these products reach the end of their patent lifecycles, the margins on these products will either be cut by at least 75% or more, or sales will go to new generic versions (the FDA calls them "follow-on" biologic medicines). Both Lilly's Humalog as well as Sanofi-Aventis' Lantus will expire soon (Novo Nordisk's Novolog/Novorapid also expires in 2013) and with companies like Novartis Sandoz unit, Teva Pharmaceutical Industries Ltd., as well as the Pfizer/Biocon deal announced this spring eager to sell generic versions of these products, it's safe to say that the losses to the companies' bottom lines will be quite severe.

Lilly, in particular, faces what has been called a "patent cliff". Not only does Humalog's patent expire in late 2012, but Lilly also faces generic competition for 4 of its 5 top-selling products including its schizophrenia drug Zyprexa, antidepressant Cymbalta, cancer drug Gemzar and osteoporosis treatment Evista. Sales of these drugs make up about half of the company's annual revenues. What's more, several Lilly's drugs in late-stage development (including an extended-release version of the type 2 drug exenatide that Lilly, along with partners Amylin Pharmaceuticals, Inc. and Alkermes, Inc. was calling Bydureon, as well as a type 1 diabetes autoimmunity drug called teplizumab being jointly developed with Macrogenics, Inc.) have all failed to meet their primary efficacy criteria. In April 2008, John Lechleiter, Lilly’s CEO cited teplizumab as one of three most promising experimental drugs in the company's pipeline. With those products unlikely to become blockbusters soon, that means the urgency for new drugs at the Lilly is even greater, and a small acquisition like Biodel might help to fill several huge voids in it's pipeline. It may work in selected segments of the sample population, but the prospects as a billion+ dollar drug seem dashed.

Sanofi's Lantus is a $4 billion drug whose patent expires in 2014, or for all practical purposes, a little over a year from now. That product is one where anything that can extend the patent would have huge financial implications, and Sanofi-Aventis has already stated it's desire to be the leader in the insulin space. Although it's rapid-acting analogue will enjoy patent protection until June 2018, the looming question is whether the advent of generic Humalog and Novolog varieties might destroy sales growth for Apidra? After all, if insurance companies can offer not one, but two alternatives for less, we can safely assume that Apidra's sales is probably NOT safe from biosimilars/follow-ons even though it enjoys patent protection for a few more years.

Ultimately, the delay in approval on Biodel's Linjeta is regrettable, but the finances for Biodel appear quite solid, and the pipeline looks very attractive for several big pharma companies who have not invested sufficiently in their insulin businesses in preparation for their eventual patent expirations, perhaps hoping they could delay regulators for many more years to come. In the meantime, the prospects for Biodel's products remain quite solid (additional trials on a small population might enable them to re-submit the application, although details won't be available until Biodel management meets with the FDA), it seems that Biodel's shares are now cheaper than they were before. For investors, this might be a good opportunity to pick up shares for a great price, with longer-term prospects of having the company sold to a bigger rival looking more likely with each coming day.