"Extraordinary Measures" Movie Tells The First Half of a Longer Story

Last weekend, (according to most reviews) a mediocre movie called "Extraordinary Measures" opened. It was the story about a motivated businessman (played by Brendan Fraser) who teamed up with a scientist (played by Harrison Ford) to, in the words of most news articles and reviews, to 'cure' a disease that fatally affects a tiny number of children, including his own children. That story was based upon the real-life story of a man named John Crowley, whose kids have a very rare condition called Pompe disease. In 2003, The Wall Street Journal featured a story on the front page about Mr. Crowley, and the same WSJ author Geeta Anad who also wrote a book entitled "The Cure" about the same thing -- now there's with a film based on her book. But Greeta's title uses poetic license quite liberally, because the reality was that Mr. Crowley accomplished pretty much what Frederick banting did in 1921, transforming the disease from a rapidly-fatal disease into a chronic disease, but stopping short of actually curing it. Mr. Crowly only partially succeeded.

Have a look at the following video:



Now truth be told, I don't know a lot about Pompe disease, and frankly, I have very pretty limited interest in learning more about the disease because it doesn't affect me. Much like people who do not have diabetes tend to have pretty limited interest in learning more about those diseaseS - I hope people will note the plurality - in fact, most people already assume they know far more about diabetes then they actually do, in fact, studies have proven that many people mistakenly believe that insulin is a CURE for diabetes, see here for details. There are plenty of know-it-alls out there whose entire knowledge of diabetes is based on incomplete or even inaccurate information, yet feel at ease sharing their lack of knowledge with people who know boatloads more than they do.

But as I suggested before, from what I can tell, Mr. Crowley achieved only a partial victory. Two of his children have Pompe disease, and although his kids have not died, they nevertheless will require treatment with a biotech medicine known as Myozyme as long as they live. Crowley's kids aren't cured, and long-term treatment will be subject to the wonders of the U.S. Healthcare "system" (a term I use very loosely). But the story is only a partial victory, I'm afraid. And right now, they have a pre-existing condition, meaning outside of Massachusetts, these kids will never be able to buy a healthcare policy at any price, barring some kind of healthcare reform legislation in Washington, which looks increasingly doubtful. Whether they realize it or not, Mr. Crowley's kids' life options will be limited due to that pre-existing condition, as they can't live the carefree lifestyles or vagabond through remote parts of the world the way some kids have the luxury of doing.

Along with that are sentiments that people with type 1 diabetes deal with all the time, like statements such as "be thankful it wasn't something worse" and "they'll get used to needles", the Crowley kids will deal with these things forever, just like people with type 1 diabetes have to do -- and they may need to fight to get Congressional funding for truly curative therapies. I don't mean to be insensitive, but these are the kinds of things people say to people (like me) as a person with type 1 diabetes all the time.

Right now, only one company makes Myozyme (that company is Massachusetts biotech company Genzyme, which has had a number of problems expanding production of that biotech medicine), and it's pricey (putting it mildly), but competition will NOT be forthcoming any time soon, and at times, it will feel like the company that makes your life-saving medication is sucking every penny from them because the company can. Genzyme has expanded rapidly by acquiring companies such as the one Mr. Crowley started. But even when the patents expire, competition may not rush in, and one look no further than the recent history of insulin as an example.

In the case of diabetes, after nearly 90 years, there are still just 3 companies selling insulin in the U.S., and indeed, throughout much of the world. And at least one of the companies involved (Eli Lilly and Company) now outsources much of it's manufacturing to third-party manufacturers like Hospira, Inc. (see more on that story here), but could theoretically decide upon a lower-cost player if they wished. The cost on an inflation-adjusted basis has increased dramatically, largely due to the lack of true competition, and innovation has been slow. All I can say to Megan and Patrick Crowley is welcome to the world of life with a chronic illness. Increasingly, medicine does not CURE any diseases (the last cured disease was polio, FYI), merely ameliorates the impact with costly ongoing treatments. Unlike type 1 diabetes, these kids probably will not take blame for the long-term impact of their disease, but I would venture to guess that over time, they probably WILL have to deal with that, too.

Human beings were not meant to maintain homeostasis with ongoing disease treatment, and by some estimates, 75% of all U.S. medical spending is now spent on treating chronic diseases, a figure that is forecast to grow in the coming years. What's more, the U.S. ranks relatively low compared to most other industrialized countries in treatment for chronic ailments (see here for more information on that). Instead of promoting Mr. Crowley as providing a CURE, I wish the author and the filmmakers had chosen to address the fact that in spite of his extraordinary measures, he only scored a partial victory over his kids' disease.

Another blogger who formerly had type 1 diabetes (one who is now insulin-free thanks to an islet transplant) Alex O'Meara, had a different perspective on the "Extraordinary Measures". He views it as an example of the emotional side of clinical trials are undertaken in the U.S. today, and something would-be trial participants should consider before enrolling in a trial themselves. Catch his perspective here.

For me, I may wait on this film and order it on Netflix when it's released on video, but what does anyone else think ... have you seen the movie, or is there any interest in seeing it? I'd love to see your comments!

Wacky No D-Blog Days

Over the years, I have featured some postings which featured one of my favorite childhood memories: Wacky Packages. When I was a little kid in elementary school, kids plastered those stickers all over notebooks, school lockers and whatnot, much to the chagrin of adults who saw them as sewing the seeds of disrespect for authority.

"Anything that happens when you're eight years old can mark you for life -- just ask Sigmund Freud!" illustrator Art Spiegelman says in the introduction to a 2008 book on the subject of Wacky Packages. "Wackies were a young child's first exposure to subverting adult consumer culture.

"Now," he adds wickedly, "thirty-five years later, that generation has matured into adults who can afford to nostalgically consume a deluxe volume brimming with that subversion. Yessirree -- I am proud to have been a worker in the debased basement of the great temple of commerce that is America's popular culture."

As it turns out, the stickers/cards had collectible value in much the same way as some of Topps other products did, such as baseball cards, with list prices for some rare stickers selling for hundreds of dollars.



Wacky packages were, at their peak around 1973 or so, in the words of an article published in the October 1, 1973 edition of New York magazine calling them a "New Fad For Children of the Skeptical Seventies", and the article went on to report that Wacky Packages were "a new twist on the classic bubble gum card ... seedling skepticism in its purest form ... Wacky Packages are selling rampant with their put-downs of products that kids have had thrown at them and into them daily by TV and Mom. From air-ball breakfast cereals to dishwashing detergents that make ladies beautiful, familiarity seems finally to be breeding contempt - and a generation of gripers." That may be a slight exaggeration, but as the artists that created the original artwork have noted, they were parodies of widely-distributed consumer products sold in supermarkets across the country. In 1979, the producer even faced new competition (albiet, only briefly) when rival Fleer issued "Crazy Labels".

A few years ago, Wacky Packages (also known as Wacky Packs, Wackies, etc.) enjoyed something of a resurrection thanks, in part, to adults like myself who remembered trading them as kids and began writing about them and trading them online via eBay, creating websites dedicated to the topic (see here and here for a few of the better and more longstanding sites on this subject, and here for a blog posting about the subject), etc. Topps finally seized upon the newfound nostolgia, and in 2004, issued a brand new series. That was followed by a few other new series in 2005, 2006 and 2007. In 2008, Topps took a break and issued a "flashback" series and another "Flashback II" series of the original 1970's artwork on brand new sticker cards. Topps is also planning another new series due out in February 2010, and emergence of coffee-table books on the subject have been published (another one is due out in April 2010), and even the miscellaneous merchandising. For example, in November, I visited Ocean State Job Lot, and came across a Wacky Packages backpack for the extraordinary price of $6.99. I couldn't resist, and bought one (although I have yet to use it, maybe I'll bring it to the CWD Friends for Life Conference this summer).

On June 10, 2008, NPR featured a story entitled "Gagging on Products" about the resurrection (see here for a link to the story):

Below are two short but (I think, anyway) interesting video clips on the topic of Wacky Packages. The first one comes from the cable channel the Food Network, and talks about the product with a major collector from the Philadelphia area. You can catch that video here:



What, if anything, does any of this have to do with diabetes?

Well, people with diabetes are kind of expected to put up with what could arguably be called a pretty s#!tty treatment protocol that is embedded with guilt (both self-guilt, and guilt impoased by others), not to mention a LOT of uncertainty, constant changes as well socially condescending attitudes about the disease that people with almost no other diseases or conditions have to deal with. For that reason, I think diabetes, and the multi-billion diabetes "industry" are really ripe for this kind of parody.

In effect, this is a call for 2 specific items:


#1) Another No-D Blog Day. As George Simmons' No D-Blog Day (NDD) proved last October (see here for details), sometimes even if we can't really take a break from all the self-care that most others take for granted, we don't necessarily have to blog about it ALL the time, and it gets kind of boring to talk about it all the time. I'd like to suggest another no d-blog day -- perhaps in a few weeks, maybe early March? To George and the other diabetes bloggers, I'll ask you to help push this concept as well.

#2) A Call to create some diabetes-related Wacky Packs of our own! (For the record, during the lapse between the time Topps discontinued and later resurrected Wackies, there was a movement of a number of people to create their own product parodies and some even sold them online, check out this guy's website for some pretty good ones, and another guy's site here)! To all you graphic-design folks (or even would-be graphic designers, we can always give a sketeched concept to someone else to finish), I'd also like to suggest (you can reach me via TuDiabetes.org here) that you parody all kinds diabetes products, ranging from insulin, insulin pens, glucose meters, test strips, glucose tablets, lancets and/or lancet devices. But, I would really encourage you to listen to the NPR story (see above) on the subject, and in particular, note the interview with one of the original Topps artists who discusses how those parody names were chosen -- for example, he notes how fellow Wacky Package artist Art Spiegelman created a kind of formula for creating them. He states: "Well, the book prints this chart, we figured out vowel combinations - Art [Spiegelman] figured out all the possible vowel combinations, so if you get something like Tide, you'd go ide (ph), bide, cide (ph), dide (ph), fide, gide (ph), all the way through the alphabet, and if you don't come up with anything, the second letter being an I, you only have to replace it with vowels, so it's tade (ph), tide, ted, ultimately, toad. And then it becomes Toad, the laundry detergent for frogs."

Also, have a look at this video from NY1, which is Time Warner's New York City cable news channel serving those of us in the 5 boroughs of NYC. We have access to that on, what else? Cable channel 1! That story can also be found here:

So what does anyone think? Any creative artists care to parody the products sold by the multi-billion "diabetes industry"? Please, do share!! Again, reach me via TuDiabetes.org.

Commentary on the JDRF "Artificial Pancreas" Announcement

Tuesday, Amy Tenderich of DiabetesMine.com was dropping hints on Twitter of a big announcement that would come out yesterday. Like clockwork, yesterday morning, many of us received an e-mail from Amy with a link to her blog post with the news which was essentially a major milestone in JDRF's ongoing "artificial pancreas" project which aims to create a closed-loop insulin pump and CGMS (continuous glucose monitoring system) that can talk to one another.

That project aims to reduce the significant manual effort required of patients and their caregivers in today's intensive insulin therapy protocols, and hopefully expand the amount of time patients spend in the target glucose range (euglycemia) doctors recommend to maintain optimal health. Interestingly, JDRF's own research suggests that the average person with diabetes spends over 12 hours a day with blood glucose levels >180 mg/dL and many others, including myself, spend more time than I should dealing with hypos caused by ever-changing basal needs, changes to insulin-to-carb ratios and the many impracticalities of try to estimate carb content (an artificial pancreas will not address that problem, BTW) in both cases, out-of-range, each day given the serious imperfections with today's treatment modalities. By developing algorithms set to a target range, rather than some arbitrary target number, they hope to significantly improve patient's well-being and their long-term outcomes.

Clinical practice has also suggested that significant glycemic volatility is much more common in type 1 diabetes when compared to type 2 diabetes (see here for a prominent endocrinologist's view on that). The full press release on this announcement can be found here, and is certainly worth having a look at.

I am by no means the first person to announce this (Amy, Kerri, the San Francisco Bay Area's JDRF Chapter blog JDRF Talk blog, Caroline Parker and several others beat me to it), but I think I probably AM probably the first d-blogger to feature the JDRF's video announcement -- I've developed a skill for lifting html code on videos hosted elsewhere and embedding them on my blog and various other social networks including TuDiabetes.org and DiabetesTalkFest.com among others, so I usually don't need someone else to post them to YouTube for me to feature them here. Anyway, the video was also featured in a mass e-mail announcement from JDRF yesterday.

Having a look at the video announcement, it seems apparent that some segments were pre-recorded in anticipation of an announcement with a yet-to-be-named partner. For example, CEO Alan Lewis says "corporate partners" in his clip, rather than naming J&J/Animas and Dexcom specifically, while Richard Insel refers to "one of the major industry players", again not mentioning exactly who those parties were). JDRF also did a mass e-mail yesterday evening on the subject, and included a ;oml the following video. I wish they would make it easier to embed the videos their sites host, but until they do, html code-lifters like me with find a workaround! The video features Alan Lewis (the CEO of the JDRF), Aaron Kowalski, the artificial pancreas project director, Jeffrey Brewer, a JDRF international board member, and of course, Dr. Richard Insel, JDRF's top research executive. Without digressing too much, you may catch the JDRF video announcement here:



Johnson & Johnson Steps Up To The Plate

I cannot help but wonder how much the death of Casey Johnson (one of the heiresses to the Johnson & Johnson fortune) might have played a role in snagging J&J as the partner (as opposed to Medtronic Minimed, another company who makes both the pump and the CGMS systems)? After all, Casey's father is one of the top JDRF board members, and her tragic death was a reminder to everyone that life with a chronic disease such as type 1 diabetes never takes a break.

The Artificial Pancreas May Not Be Quite As "Dumb As A Brick", But Still Needs Work

As Amy correctly referred to this in her write-up, the announcement is really about more of a "first-generation" artificial pancreas that will be developed, because it won't really be closed-loop just yet (actually all that was announced was a commercial partnership; the FDA still has to approve whatever the partnership ultimately produces). This week's announcement may reduce (but will not eliminate) the regular "instructions" as author Dan Hurley (Diabetes Rising) described them required from the patient -- it will be, after all, a first-generation device. If you recall, when I reviewed his new book (released a few weeks ago), Mr. Hurley lamented:

"I finally decided to go on a pump in 1999, after my insurance company agreed to pay much of the cost. On balance, I found it made life easier by allowing me to make minor adjustments in my insulin rates on the fly, but resulted in little change to my A1C numbers. And my lows remained every bit as common as my highs. Essentially, it was just another way, albeit incrementally better, to get the same old insulin I'd always used. And while friends and family often assumed that the pump worked like an artificial pancreas, giving me only as much insulin as I needed, in fact, it was as dumb as a brick, following only the instructions I gave it."

Those of you who read Close Concern's diaTribe understand that what a first-generation system basically means the wearer will still have to "warn" system out by telling the system you'll be eating something so it knows enough to anticipate some carbs, but it is a step forward in a project that has been a dream for many people and in the works for decades. I would not go so far as to call it a dream for every type 1 diabetes patient, because as message boards on the online social media community suggests (as well as Caroline's blog, noted above), the idea is not universally desired by people with diabetes, as much as the companies who stand to profit from this technology would love that to be the case. To be sure, some would like it, but many others complain the CGMS sensors aren't accurate enough (particularly at the hypoglycemic level), the insulin is still too slow, and still others complain the devices are still too invasive and/or bulky and unattractive. I agree with all of those sentiments. But it is a step in the direction and a concrete one, at that.

My Type 1 Pancreas Works Fine, Thank You, It's My Islets That Don't Work

Personally, I've always hated the term "artificial pancreas" because my pancreas works just fine, thank you, but my Islets of Langerhans have been destroyed by autoimmunity. That means its really more accurately described as artificial Islets of Langerhans, and to call it an artificial pancreas implies that patients with type 1 diabetes have broken pancreases, when in fact, aside from no longer making insulin, amylin and glucagon, the pancreas continues to produce all of the digestive enzymes necessary for survival! In fact, the Islets constitute less than 1% of the total organ mass, even if that 1% represents a critical piece of the total. Anyway, this effort was about a partnership arranged by the JDRF with Johnson & Johnson's Animas insulin pump business (truth be told, that was an acquisition by J&J a few years ago, it was founded by Dr. Katherine Crothall, MD, but I digress).

J&J's One Touch Business Not Included?

What makes this partnership a bit unique is that J&J's gigantic One Touch business that makes testing supplies for the company doesn't appear to have a big role in the project, at least not now. Instead, another startup, in this case Dexcom, is the CGMS involved in the project. One Touch does not presently have an approved CGMS device on the market (although competitors Medtronic Minimed and Abbott do). One additional element of interest about this announcement was the fact that JDRF prominently noted that this partnership was not exclusive, which suggests that the organization is also seeking other companies to join in to help with commercialization.

Make Them Smaller, Cheaper AND Guaranteed Covered By Insurance, Then (Maybe) I'll Consider It

I'm not crazy about this announcement because its just a partnership and its not exactly close to commercialization, but I also cannot be too critical. JDRF has spent some money on this (although the organization does not disclose their full budget for it), but from what I can discern, they've spent far less on this project than many other ideas that failed to pan out, plus they have gotten big medical device companies to participate (I'm still p!$$ed JDRF funded the CGMS studies needed to gain insurance coverage, as the companies that make those things have reaped all of the profits and could have funded those for themselves). For many people, these devices could make lives infinitely easier. But JDRF is claiming at least another 4 years is needed before this is ready, and I'm not getting any younger waiting for this device to emerge. This, of course, assumes that the U.S. Fatalood and Drug Administration get's its own act together and moves swiftly to approve the devices, and the way that agency moves, I'm inclined to doubt that's likely to happen on-time.

But I do see why there is reason to be excited for many people, and when it comes to diabetes management, that's typically in short supply. I'll just say this does prove JDRF has the ability to put commercial partnerships together, which is indeed beneficial to people with type 1 diabetes.

USA Today: "Double transplant for type 1 diabetes brings troubles, gifts"

Just a little over a month ago (on December 9, 2009 to be precise), I posted a Timewarp Tuesday posting I called "The Needle And The Damage Done". The reason was largely because I was going through my own file archives and wanted to share the story shared by Scott Bowles, a reporter for USA Today which chronicled his own wait for a kidney/pancreas transplant back in 2000, which ended in successful surgery and insulin independence for the first time after 20 years of life with the autoimmune disease.

My timing turned out to be rather fortuitous, because today (on Monday, January 11, 2010), USA Today happened to feature an update on Mr. Bowles' transplantation experience, his life as a former person with diabetes, and some difficulty he's experienced as a result of the transplantation surgery on this, the ten-year anniversary following his life-transforming surgery. It also comes, ironically enough, on the 88th anniversary of the first reported treatment with insulin.

Ultimately, I will share all of the pictures and text to this story, but for the time-being, here is the text content of this real-life experience post diabetes.


Double transplant for type 1 diabetes brings troubles, gifts
By Scott Bowles, USA Today
January 11, 2010

Ten years ago Tuesday, USA Today's Scott Bowles had a kidney and pancreas transplant to treat his juvenile diabetes. He kept a journal of the experience, which ran as a series in the newspaper and in his book, "The Needle and the Damage Done". Bowles, 44, a film reporter in Los Angeles, looks back at the decade and life after the surgery.

Albuquerque, April 7, 2009

Denzel Washington is going to have to wait.

The star is on a nearby stage, rehearsing for his film The Book of Eli and waiting to give me a 15-minute interview before shooting begins.

But I'm not going to make it. I'm on the floor of a publicist's darkened office, on my back, trying to slow my breathing and fight off the nausea and heart palpitations that are racking my body.

Again.

It has been 10 years since I opted to treat my diabetes with a kidney and pancreas transplant, a decision that, for the first time, I'm beginning to question.

I find myself on a hospital gurney with frightening regularity lately. Where once I was going to the hospital every six to eight months, now I'm there every six to eight weeks. My weight is down to 139, lighter than I was in college. Three days without nausea or a racing heart feels like a good stretch of health.

More frightening, doctors aren't sure how to keep my body from breaking down. They've diagnosed me with two post-transplant illnesses: cyclic vomiting syndrome (CVS) and atrial fibrillation. CVS is a powerful wave of nausea that hits without warning and can last hours, leaving me heaving long after my stomach is empty.

The nausea depletes me of electrolytes and minerals, which sends my body into the more dangerous complication: atrial fibrillation, a condition in which the heart pumps twice as fast as normal but circulates only 60% of the blood, raising the risk of a blood clot and stroke.

Today, I'm in the throes of both complications. I'm rushed to New Mexico University Hospital, where nurses are having trouble finding a vein. I've had so many blood draws over the decade that my veins have scarred and it's difficult to find one that's usable.

They try two sticks in the left arm. No luck. One in the right. Same result.

A nurse suggests mining my neck. I close my eyes: This is the one place I thoroughly feel the needle. The vein works all right; it's dashing us both in arterial spray, too much for her to secure an intravenous tube. Finally, she sinks the needle between the fingers of my right hand and finds a vein.

After a bit, I feel the medications open my lungs and nudge me toward sleep.

But not before I think to myself: I can't keep doing this.

Los Angeles, July 14, 2009

My doctor for the past 10 years, Michael Brousseau, has me in his office. My mother is here, too. She has traveled from Atlanta to meet with physicians and brainstorm.

Brousseau is frustrated. I'm on a dozen anti-nausea medications — some of them designed for cancer patients on chemotherapy — yet nothing works with consistency.

He connects me with two more specialists, who will focus on my stomach and heart. "Something has to work," he says. "Because right now, you're not functional."

The words throw me. I had this surgery Jan. 12, 2000, as a salvo against the disease, which over 20 years claimed both kidneys, one-third of my sight and almost all hope that I'd reach 50 with my vision and limbs intact.

And for five years, it seemed, the transplant was the solution. To this day I've had no rejection episodes and not a drop of insulin.

But the new complications are frighteningly quick and forceful. I was never staggered by an insulin reaction or high blood sugar as I am by these side effects.

We drive home, and I excuse myself to the bathroom. I run a hot bath (the one treatment that seems to settle my nausea) and turn up the radio so Mom can't hear me lose my composure in the tub.

Maybe I don't beat my body's demons. Maybe I already was as healthy as I'm ever going to be.

July 16, 2009

Mom and I are walking through the mall when I lose my balance. The new medications are interacting poorly, leaving my head swimming and my legs unreliable. I flop in a mall seat while Mom goes for something to drink.

A woman who has been watching from a nearby bench walks toward me. She holds a package of gum and offers me a piece.

I'm not sure how to respond, so I take it and thank her. She shakes her head — she doesn't speak English — but smiles and offers another piece.

The gum does nothing, the gesture everything. By the time Mom is back, I'm already feeling better, energized by the random kindness of the woman, who nods and smiles as Mom and I pad off.

This disease can offer such odd, sweet consolation prizes.

Sept. 16, 2009

A nurse calls me at home, the first time I've heard from my insurance company unsolicited.

"It appears you've been having some complications of late," she says. "Is there anything we can do?"

I'm cautious. I'm getting two dozen bills, letters from hospitals and benefits explanations every month now, and I must be signaling a red flag with the insurance company. My anti-rejection drugs have jumped from $1,200 a year to $2,800. And that doesn't include hospital stays, ER visits or nausea medications that run $150 a week.

No, thank you, I tell her. We have specialists working on it.

She presses a little more, asking for some details of my recent hospitalizations. She gently asks whether this is a new problem or something "that might have been pre-existing."

I freeze. I know what that phrase means. It means you've become too expensive to keep healthy. No, I say flatly before getting off the phone, it's a new problem.

Fortunately, I didn't have to lie. This is new. I could use help. But I'm not sure she's offering it, and I would have told her my nose wasn't a pre-existing condition if my insurance were at stake.

Nov. 1, 2009

My good friend Jocelyn Smith is visiting when I feel my hands and feet go numb — the surest signal I'm headed into atrial fibrillation.

Without a word, she jumps into action. She eases me into her car, drives me to the hospital and gives the doctors the rundown on my medications and symptoms. She stays the duration of the six-hour wait for a bed.

Somehow, this trip to the hospital is easier than the others.

Maybe it's seeing Jocelyn oversee the chaos like a M.A.S.H. nurse. I've watched as my friends and family turn into a team of first responders: paramedics, doctors, ambulance drivers. All without asking or asking anything in return.

Not that there's any way to repay what they've given me.

Dec. 11, 2009

I'm beginning to understand how dogs improve and lengthen the lives of the elderly. Mine are making this place more homey.

PAW PRINT POST: Dogs are family

When I'm ill in the bath, I notice, they quit roaming the house and cram into the bathroom. My golden retriever, Teddy, curls up by the tub. Esmé, a diminutive Boston terrier who acts as his orbiting moon, nestles into his belly.

I don't want to be that crazy dog guy, but I'm convinced their company helps. It's comforting to reach over the tub and bury my hands into that warm, tangled fur pile, something that could have sprung from Where the Wild Things Are.

I've read the studies that say domestic animals have learned over the years to befriend humans to maximize food and shelter from us.

But I prefer to think they can't stand the thought of me being alone or sick.

Dec. 25, 2009

This could be a strange Christmas. Because the nausea and A-fib can strike so suddenly, I can't risk being on a plane for five hours to visit my family in Atlanta. This will be the first Christmas I don't make it home for some part of the holiday season.

I wake up ready to dread the day, but my body has surprised me. No nausea, no heart-skipping.

I decide to spend the day visiting people dear to me: Anthony Breznican, who cooks for me more than I do; Luz Elena Avitia, who has become a surrogate parent to my dogs when I'm sick; and Michael Ingram, an old friend who offered me one of his kidneys 10 years ago.

The trip isn't without risk. Luz and Michael are in San Diego, and the complete drive will take at least five hours — as long as a flight.

But I'm tired of my body caging me. I stuff a few meds in my jeans and hit the road.

The day flies. Everyone is in good spirits, my heart is behaving and by the time I'm driving back, I've forgotten how long I'd gone without a moment of nausea.

When I get home, I realize that I haven't opened any presents under the tree. I know it's corny, but this Christmas — filled only with people I love — has a Seuss-ian feel to it. I go to bed without touching a gift. I'll do that tomorrow.

Tonight, I'd like to remain that Who in Whoville.

Jan. 9, 2010

Tuesday marks what I consider my 10th birthday: the day I received my organs.

It also marks the day Valerie and Leroy Flegel took their 21-year-old son, Samuel, off life support.

I have trouble reconciling this. How does that much despair create that much hope?

Samuel was, by all accounts, an extraordinary young man. Born with a learning disability similar to dyslexia, he overcame it to earn his GED and become an engineer for Red River Valley and Western Railroad in Wahpeton, N.D.

He was riding home from a New Year's party in Fargo in 2000 when he hit a parking lot abutment hidden in snow. By the time police found him, he was brain-dead, though the subzero temperatures kept his body alive.

Now I carry him.

For some reason, I rarely get sick around the anniversary date, and this time is no different. I wake up hungry, energized. Healthy. I hop in the car and drive for a doughnut, something I could never have eaten as a diabetic.

On the drive back, I'm a little angry at myself for being so self-pitying, for questioning this fight. There is no beating diabetes, just changing the complications. But at least I have a chance for better health, something Samuel never got.

And perhaps more than any other anniversary, this one reminds me that I do not fight alone. Through all this, friends have become family and family has become closer than it has ever been. Strangers have offered whatever they have. I think of them and it propels me, literally.

I am awake now, opening up the accelerator as I drive home. Music rattles the windows of the car. I don't want the drive to end.

I speed past the exit for my house. The morning is bleeding into afternoon, and it's too warm, too nice to stop moving. I'm going to drive until I run out of gas.

For every day I spend sick or in a hospital, it seems, I receive one that is equally fine. That's where I discovered the unexpected gift of diabetes, one that I would never return: the capacity to recognize and enjoy the moment.

A nausea-free morning. A symptom-free afternoon. A good day.

Like this one.

© Copyright for this article 2010, USA Today, a division of Gannett Co., Inc. and journalist Scott Bowles.

The Business of Diabetes: Big Changes May Be In Store For The U.S. Insulin Market

This posting originally started out with a press release I caught which I felt might be of interest to my readers, but as I began researching the subject further, it evolved into a broader discussion of the insulin market as we know it today.

Whether you realize it or not, the U.S. insulin market could soon see some of the most profound changes the industry has seen in decades. The reason: competition could soon change the dynamics of a once-comfortable oligopoly which we can only hope will result in a much more competitive and dynamic market. One look back to the 1970's U.S. automobile market to see what might happen to insulin in the coming years if new competition enters this staid market.

Until the 1970's, Detroit's "Big 3" dominated the U.S auto market and by many accounts, resulted in laziness and arrogance among them (there is also a "Big 3" in insulin providers, which makes this comparison especially relevant). Product quality wasn't really great, fuel-efficiency was practically non-existent, and prices hardly resembled what could be called a dynamic free-market. That very much resembles the U.S. (and worldwide) insulin market today; the barriers to entry were high. But in the 1970's, companies from Japan and to a lesser-extent, Germany sold high-quality cars that were an ideal fit for the OPEC oil embargo that occurred in 1973. Of course, many consumers were pleasantly surprised and Toyota and Honda would go on to become household names -- and would ultimately unseat GM for worldwide leadership in the auto industry. Germany focused on quality too, but realized it could not really compete in mass-market products, effectively creating a new paradigm for luxury cars and that the country retains leadership even today. The insulin market badly needs competition. The current market leaders have steadily increased prices their and abused the private healthcare providers because the barriers to market entry for competition is quite high in spite of the fact that the technology to make insulin is has existed for decades. The insulin cartel has also been slow to introduce much in the way of innovation, and has abused their market leadership in much the same way as GM abused its leadership in autos back in early 1970's by aggressively increasing prices above the rate of inflation without consummate merit in product design or quality because there really were no practical alternatives.

Insulin: Once The Deprived Stepchild of Research Investments Until the 1990's; Then Transformed Into A Cash Cow

It used to be that insulin, first discovered in 1921 by Canadian researchers, was viewed by the pharmaceutical industry as the neglected stepchild to more creative, interesting and profitable new type 2 diabetes medicines (most of which were oral meds), leaving insulin for all practical purposes, desperately starved for research dollars and talent who tended to migrate towards the much larger and more lucrative ailment of insulin resistance.

In terms of money spent, some analysts estimate that until the early-1990s, the total dollars spent on insulin resistance treatments dwarfed the dollars spent on insulin treatments by a ratio of as much as 90 to 1, meaning for every $1 spent on insulin research, $90 was spent investigating new type 2 treatments. But in the mid-1990's, with 1996's FDA approval of the first man-made insulin-like molecule (known as insulin analogues), that business dynamic was turned upside down (see here for more on that subject). Soon, researchers outside of an academic setting began to see potential in interest in insulin, a hormone which remains remarkably well-preserved across most different species of animals (humans could actually use fish insulin to manage their blood glucose if they had to).

The reason for this change was that researchers discovered they could patent-protect "proprietary" molecules that were similar to (but not exactly the same as) the hormone produced endogenously by virtually every primate under the sun -- except, perhaps those hapless individuals with type 1 diabetes and some patients with later-stage type 2 diabetes. Insulin became something of a cash-cow to the drug industry, and the margins have steadily increased, which stands in stark comparison to many oral diabetes drugs whose prices have plunged thanks to vibrant generic competition (today, there STILL is no generic insulin, see here, here and here for some more background on that anomaly).

Once insulin lispro was approved by the FDA in 1996, the floodgates were effectively opened. Although relatively few of these molecules have actually made it to market (as of today, just 5 have been approved: lispro, aspart, glulisine, glargine, and detemir), there has been no shortage of interest from big pharma and big biotech.

The Future of Insulin Therapy Includes Some Names You Might Not Recognize ... Yet!

Once the floodgates were opened, what was once a boring, not very dynamic industry saw millions in new investments from researchers and startups (as well as established players) eager to cash in on insulin's new-found status as a cash cow. Today, there are at least 3 late-stage insulin formulations (meaning they have all either completed Phase III clinical trials or are pretty close to and are planning to apply for FDA approvals in 2010), and several others aren't too far behind. Interestingly, none of the newest insulin innovations are from the dominant players in the business (Novo Nordisk, Sanofi Aventis or Eli Lilly & Company), but from startups.



Biodel's VIAject

On December 30, 2009, the first newcomer announced a significant milestone: Danbury, Connecticut-based Biodel, Inc.'s VIAject was submitted for FDA approval, and is widely expected by analysts to be approved without significant delay. Interestingly enough, VIAject isn't an insulin analogue at all, but humble, regular old insulin containing some already FDA-approved additives which prevent the molecule from forming hexamers which normally delay the insulin molecule's absorption into the bloodstream. Because of this, the company was able to apply using section 505(b)(2) of the Federal Food, Drug and Cosmetic Act which governs the review of a New Drug Application (NDA) for a modified form of a previously-approved product. Because of this, the company's VIAject is likely to encounter less scrutiny than a brand new drug filed under section 505(b)(1), which requires original clinical trial results to be submitted with the application. In addition, this saves the company significant money.

Biodel was not assured to be the first out of the gate (it still may not be, as the FDA is set to make a ruling on MannKind's Afrezza (which was formerly called Afresa, but the company reports that the FDA requested a name change to avoid confusion with another drug) by January 16, although the FDA can always delay, and some reports hint at a later date, the company suggested otherwise). Biodel encountered some thorny issues related to its Phase III trial results in India with the FDA, and the reason was because the blood test results were tainted by the hot India temperatures, and when those samples are excluded from the results, the FDA found the Indian trial results were comparable to those in the U.S. and Germany. I'll reference back to this in a minute.

Generex's Oral-Lyn and MannKind's Afrezza

In addition to Biodel, there is also Generex's Oral-Lyn, which I wrote about previously, and MannKind's Afrezza which I noted in the preceding paragraph. As I also noted, the FDA is set to make a ruling on Afrezza's approval by January 16, 2010 although the FDA can always delay, and although some reports are hinting at a later date, the company is suggesting otherwise. MannKind has even bought its own factory to make insulin, rather than using third-party contract manufacturers (as Eli Lilly is now doing for most vials of insulin, including Humalog sold in the U.S., and most of the others including the other startups, are using contract manufacturers rather than making insulin themselves). In March 2009, the company submitted a New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA) for it under section 505(b)(1) of the Federal Food Drug and Cosmetics Act, although the FDA is taking a much harder look at the impact on the lungs, so this product still hasn't yet received approval. But in January 2010, Bloomberg reported that company executives expect U.S. FDA to approve its version of inhaled insulin, which suggests the company has received indications from the FDA that it will ultimately be approved.

There are also at least 5 other earlier-stage "advanced" insulin and/or insulin analogues that are known about from established players in this industry including Novo Nordisk, Lilly, Sanofi Aventis just to name a few. Even Merck, now in a place to make the insulin itself after acquiring Schering-Plough (now one of the largest contract manufacturers of insulin on earth with its Organon N.V. unit based in the Netherlands), is reportedly shopping around for new insulins.

Halozyme Therapeutics

Another player is San Diego-based Halozyme Therapeutics, which I mentioned a while back. Like Biodel, Halozyme's work would use additives it says target the "extracellular matrix" (subcutaneous) to insulin and/or insulin analogues to speed them up. The company is also doing a number of research trials comparing their additives to regular insulin, as well as insulin lispro, aspart and glulisine. Although the company has done Phase 2 clinical trials it still needs to do much larger Phase 3 trials which require many more participants and therefore cost a LOT of money. In the company's 2009 Investor Day presentation, the company elaborated somewhat indicating that the company is targeting 2014 to be ready for prime-time, and it's likely that the company will partner with an existing insulin manufacturer (or possibly more than one) to commercialize its product.

Thermalin Diabetes

The original news story behind this posting was from December 14, 2009, when news broke of another potential player hoping to cash in on the proprietary insulin-like formulations, this one based in Cleveland, Ohio whose name you may see more of in the coming years: Thermalin Diabetes, Inc. A detailed press release indicated that Case Western Reserve University in Cleveland had granted an 18-month, exclusive option to the Cleveland, Ohio-based startup regarding an entire portfolio of insulin analogues.

Richard Berenson, executive chairman of Thermalin Diabetes Inc. says he has no fantasies about making a couple billion dollars from Thermalin over time. Presently, insulin is a $12 billion market which is growing quite quickly. That growth in spending on insulin is not due as much to growth in new patients taking insulin, but developments which have enabled manufacturers to develop more costly insulin-like molecules called insulin analogues and cover these inventions by patents, meaning patients today pay significantly more for insulin than they did 30 years ago on an inflation-adjusted basis. The Express Scripts annual Drug Trend Reports for the past several years (in particular, the 2007 report looked very closely at insulin spending) made it quite clear that spending increases in spending on insulin are not due to increased utilization, but higher prices in recent years.

While proponents of new insulins are very quick to make bold claims about how much these proprietary new insulin formulations have done to improve glycemic control, this claim is not backed by very solid statistics in clinical practice. Virtually every major meta-analysis (done in countries ranging from Australia, Germany and the UK to Canada) to compare insulin analogues to first-generation insulin varieties has raised questions about to whether these more costly so-called "innovations" have really been the big advancement in glycemic control their proponents seem to suggest, because the average glycosated hemoglobin (HbA1c) results have barely budged (they have come down slightly in recent years, but very slightly, and far less than the increase in spending would appear to justify) over the same period of time. That's not to dismiss them altogether: insulin analogues may very well make patients' lives easier, but healthcare providers cannot point to substantive quantitative reductions in average glucose levels alone as justification for the increased spending on these products.

Berenson however, puts things into perspective, suggesting that even if Thermalin captures a small slice of the market, it could be a very big deal for investors.

"... an exit in the regular drug-acquisition range of a couple hundred-million [dollars] is not crazy," he said. "And this is with a capital efficiency of investment of less than $10 million. So that's why I think there's interest in the angel community."

To date, Thermalin Diabetes has closed more than $275,000 in seed financing from individual investors. The company has also received a $254,000 Phase 1 Small Business Technology Transfer Grant from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (NIDDK). The latest Case Western grant is intended to support the development of one of Thermalin's portfolio of insulin analogues through large animal testing. When the company achieves the grant's specific aims, it will be eligible for significant additional grant funding to advance the compound to human clinical trials. This latest investment from Case Western is a sign that the underlying technology appears promising in terms of its likelihood to advance further. Of course, Case Western has hedged its bets a bit in that the company must reach certain milestones in order for it to exercise its option to obtain an exclusive license on therapies designed to help patients with diabetes.

Thermalin's name is derived (at least in part) from one of the primary product's key advantages: namely the molecule's ability to maintain its stability even without refrigeration at temperatures up to 40 degrees celsius (approximately 104 degrees fahrenheit). How is this accomplished?

A researcher at Case Western named Dr. Michael Weiss (David Edelman of Diabetes Daily did a podcast interview with Dr. Weiss in June 2008, see here for that very interesting interview) solved that problem by stretching the double-chained insulin molecule into to a single chain, Berenson said.

"Thermalin is a new kind of insulin," Weiss said. "Like insulin, it's injected or used in a pump. And like insulin, it causes the blood sugar to go down, and so it can be used to treat diabetes. But it's improved from insulin, in that, at high temperatures, it lasts for weeks and even months. It's almost indestructible at high temperatures, and so it affords enormous … lifestyle convenience to patients."

Is Heat-Resistant Insulin A Surefire Blockbuster?

I don't know. In 33 years of using insulin -- including when I wore an insulin pump, I NEVER had problems with heat breaking down my insulin and rendering it ineffective. But I also live in a place with a pretty moderate climate -- not the desert of Arizona or the subtropical climate of say, South Florida. Indeed, there is an entire group on the professional social network LinkedIn called "Change CVS/Caremark's Insulin Shipping Policy" pushing to change that pharmacy benefits manager's (PBM) current insulin shipping policy which violates the manufacturers' temperature guidelines. For most people, its a non-issue, but for residents of some states including Florida and Arizona, this is a big issue for patients ordering a 90-day supply of insulin by mail.

Biodel's Phase III Clinical Trial Problem in India Due to Heat

We need look no further than Biodel's Phase III human clinical trials earlier last year on its new rapid-acting insulin VIAject as a vivid example of how high temperatures nearly killed that company's Phase III clinical trial outcomes from one of 3 legs of its Phase III trial; fortunately those issues were resolved.

But VIAject's Phase III trials were undertaken in the United States, Germany and India. The results from the U.S. and Germany clearly demonstrated superiority (based on the narrow FDA evaluation criteria, which looks primarily at HbA1c reductions) while data from the pivotal Phase III clinical trial for patients with type 1 diabetes undertaken in India were found to be anomalous when compared to data from the U.S. and Germany for the same trial. When HbA1c data from patients in India were included in the analysis, change in HbA1c favored the Humulin R treatment group. Data from India was shown to be statistically different, which in the company's view made these data not comparable to the data collected in the U.S. and Germany. The analyses by independent clinical and regulatory experts at the FDA suggested there were specific factors that explain the results in India, specifically heat.

Among the causes noted in the briefing package, an identifiable subset of blood samples from patients in India was found to be compromised due to excessive heat exposure in transit to a central laboratory. When the compromised samples are removed from the efficacy analysis, non-inferiority in both the Type 1 and Type 2 trials is achieved, and the company is able to file a NDA (new drug application) for VIAject pretty much on schedule. Although the heat was not identified to have impacted the stability of the insulin molecules in either the control or test group, it was noteworthy enough to have compromised a sample of the blood samples while in transit to the labs, and that same heat could lead to a breakdown of the insulin molecule itself in a place where electric outages occur regularly and a significant portion of the population do not even have access to electricity.

Life of a Child Example Suggests Third-World May Be Opportunity for Thermalin -- If they Can Pay For It

One of the things that has angel investors more excited about this company is not necessarily the prospects for the product in the developed world, however, but in the developing world, where many patients do not even have electricity to keep their insulin refrigerated. It's a huge market and the incidence of diabetes is growing rapidly in many of these countries.

Thermalin might prove attractive (such as for patients with insulin pumps who occasionally find that they need to refill their reservoirs because higher temperatures can cause their insulin [or analogue] insulin to break down). But the bigger advantage for the developed world is that this insulin analogue, because it is a single-chained molecule, it is also extremely rapidly-acting -- supposedly much faster than today's first-generation insulin analogues such as insulin lispro or glulisine.

Preliminary evidence also suggests that Thermalin might also pose less risk of a cancer or weight-gain than first- or second-generation insulin analogues. Dr. Weiss also has developed long-acting insulins, which Thermalin could commercialize in the future.

The prospects in developing world are very attractive due to the sheer size of the market. Two years ago, I attended the New York premier of a documentary, which aired on cable television for the first time this year on World Diabetes Day on the Sundance channel. The reality for people living with type 1 diabetes in the developing world is quite unlike what anyone from the developed world has to deal with. In that film, one of the children with diabetes is a little girl from Nepal named Anupa, who has to walk six to eight hours to get down the mountain only to then catch a bus (which her family may not be able to afford), and then travel by bus for another few hours to get to the capital, Katamandu, where she can get insulin. Her house has no electricity, no telephone, and no refrigerator. She carefully puts her insulin into a container inside the house, and then buries the container in the dirt floor to try and keep it closer to the ideal temperature, hopefully preserving her insulin long enough until she can trek into Katamandu again for some more. You can catch the clip to that film here:



The one disconnect in my mind, is that patients in the developing world cannot typically afford to pay premium prices for drugs, and it's less clear that heat-resistant insulin is a big enough advantage to justify higher prices to the developed world, but its speed should help. Whether that is sufficient to make it a blockbuster that enables the Western world to subsidize prices for the developing world remains a big question. The rapid-acting insulin market is becoming a crowded space, as this posting suggests given the sheer number of potential competitors. But that isn't the only thing Thermalin has in its business plan.

Arsenal of More Than 100 Analogues

Thermalin is working on more than just faster,heat-resistant insulin molecules. The company is also reportedly testing a portfolio of more than 100 different insulin analogues discovered by Dr. Michael Weiss at Case Western Reserve University School of Medicine, and Thermalin Diabetes believes the company is poised to address a number of significant unmet needs in many segments of the $12 billion, suddenly rapidly-growing insulin market. Among the other concepts being pursued are a longer-lasting analogue than current products. Of course, the company isn't alone. The already well-established competition is also pursuing similar products, but Thermalin believes they have a broader portfolio. One concept the company is also pursuing is another long-acting analogue, but unlike Sanofi Aventis' Lantus product, Thermalin believes their does not have mitogenic tendencies, for which there are some concerns may increase cancerous growths with long-term usage. Clearly, angel investors think this company has a lot of potential.

SmartCells' Smart Insulin

Of course, I haven't even mentioned SmartCells, Inc., a Beverly, Massachusetts-based startup that is developing a method to encapsulate human insulin nanoparticles in a polymer that would actually "detect" a diabetic's glucose levels automatically, and therefore release only the appropriate amounts of insulin at precisely the right time to keep blood sugar levels steady. (Catch my interview with the company CEO Todd Zion here) Of course, there was also the $1 million grant from JDRF announced last year which will support testing the safety and efficacy of Smart Insulin in preclinical type 1 diabetes trials. This partnership is intended to accelerate the product's development and reduce the time needed to progress to human testing. The grant is part of JDRF's innovative Industry Discovery and Development Partnership Program (IDDP), which supports companies developing drugs, treatments, and technologies to address type 1 diabetes and its complications. SmartCells still has to accomplish a number of milestones, since it hasn't yet even gone to Phase I human clinical trials, but this product could potentially render many of the other insulin analogues and insulins with special additives to make them even faster completely irrelvant, so it deserves mention here. The company has had no trouble in attracting venture capital, and in addition to the JDRF grant, the company has also secured financing from the U.S. National Institutes of Health (NIH)/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), so the prospects look quite promising, although SmartCells still has a few years before even approaching commercialization, but the prospects look positive.

What's Next?!

This year, we are set to see a number of new insulins from a number of different companies. The success of these companies will depend not only on the quality of the products, but also the companies' ability to penetrate the pharmacy benefits managers (PBMs) such as Medco Health Solutions, CVS/Caremark and Express Scripts, who not only are among the biggest buyers if insulin in the U.S., but they also pay for over 80% of all prescriptions filled in the U.S. today, and could be even larger if Congress passes some type of healthcare reform and adds another 47 million to the system. But having more competition in the insulin market can be nothing but a benefit for people with diabetes!