Close Concerns Weblog

Nastech and Amylin ~ early stage deal

So we had to look twice when we saw this headline - we figured Nastech and Amylin might be working on some sort of PYY formulation together (what we fondly call the satiety drug, which we haven't really heard a lot about) but in fact, this is a deal looking at potential use of Byetta delivered nasally. Hmm! It makes sense because Amylin has been talking a lot about alternate delivery systems. This could be pretty alternate! We think of it as an option play for Amylin: 1) They have Byetta, which is doing incredibly well - so well that they have to, a year in, discourage for a bit of time new users - in our view, no way is more winning to try to attract people to the drug longer term than to tell them they can't have it short-term; 2) They have LAR longer term, which looks fantastic; 3) see above. So, it seems odd to even consider a nasal application? Wouldn't there be dosing issues? absorption issues? etc? Probably, but we guess it looks good enough to consider. Who knows how much downside there is for Amylin - probably not that much.

The release (see below) doesn't say a whole lot about financial terms, but the early, early stage (it's still preclinical though is going to the clinic soon) is reflected in the ~$90 million top milestone fee, which, while not chump change, certainly doesn't reflect revenue that's expected for Byetta injections (regular or once weekly). Then again, we don't know what the royalty looks like, so it's a bit difficult (by design we assume) to get a real sense of the deal. Amylin is paying for all the development, and thank goodness, has overall responsibility for the development program. Excellent!

We've made some calls and may be back with more on this depending on what we learn. We do view the association with Amylin as at least a modest positive for Nastech.

Nastech Pharmaceutical Company Inc. Enters into Development and License Agreement With Amylin Pharmaceuticals, Inc.
BOTHELL, Wash., June 26, 2006 /PRNewswire-FirstCall via COMTEX News Network/ -- Nastech Pharmaceutical Company Inc. (Nasdaq: NSTK) announced today an agreement with Amylin Pharmaceuticals, Inc. to develop a nasal spray formulation of exenatide. Preclinical studies of the formulation have been completed in preparation for initiating studies to determine feasibility in human subjects.

Under terms of the agreement, Nastech will receive milestone payments and royalties on product sales. If feasibility is successful and the program moves forward, milestone payments could reach up to $89 million in total, based on specific development, regulatory, and commercialization goals. Royalty rates escalate with product success. No other financial terms of the agreement were disclosed.

Amylin and Nastech will jointly develop the nasal spray formulation utilizing Nastech's proprietary nasal delivery technology, and Amylin will reimburse Nastech for any development activities performed by Nastech under the agreement. Amylin has overall responsibility for the development program including clinical, non-clinical and regulatory activities, while Nastech's efforts will focus on drug delivery and chemistry, manufacturing and controls (CMC) activities. If a supply agreement is reached between the companies, Nastech may supply commercial product to Amylin and their exenatide collaboration partner, Eli Lilly and Company.

"Amylin is a leader in developing innovative therapeutics and we are very excited to work with them," stated Steven C. Quay, M.D., Ph.D., Chairman, President and CEO of Nastech. "This collaboration validates an important aspect of Nastech's business strategy, which is to conduct feasibility studies with biopharmaceutical companies and later convert them into development and commercial manufacturing collaborations. We will continue to work with our collaboration partners to provide therapeutics that promote a healthier life."

About Nastech

Nastech is a pharmaceutical company developing innovative products based on proprietary molecular biology-based drug delivery technologies. Nastech, along with collaboration partners, is developing products for multiple therapeutic areas including diabetes, inflammatory conditions, obesity and osteoporosis. Additional information about Nastech is available at http://www.nastech.com.

Nastech Forward Looking Statements

Statements made in this press release may be forward-looking statements within the meaning of Federal Securities laws that are subject to certain risks and uncertainties and involve factors that may cause actual results to differ materially from those projected or suggested. Factors that could cause actual results to differ materially from those in forward-looking statements include, but are not limited to: (i) the ability of Nastech to obtain additional funding; (ii) the ability of Nastech to attract and/or maintain manufacturing, research, development and commercialization partners; (iii) Nastech's and/or a partner's ability to successfully complete product research and development, including preclinical and clinical studies and commercialization; (iv) Nastech's and/or a partner's ability to obtain required governmental approvals; and (v) Nastech's and/or a partner's ability to develop and commercialize products that can compete favorably with those of competitors. Additional factors that could cause actual results to differ materially from those projected or suggested in any forward-looking statements are contained in Nastech's most recent periodic reports on Form 10-K and Form 10-Q that are filed with the Securities and Exchange Commission. Nastech assumes no obligation to update and supplement forward-looking statements because of subsequent events.

Metabolic Syndrome - It's not over yet!

We sort of punted on covering obesity in our latest DCU, because we thought we'd rather do a whole issue on it (next month, August's issue) rather than cover only sketchily what happened at ADA and still be pressed for space. We also wanted our issue to cover two other meetings in June besides ADA - first, the Endocrine Society, which started yesterday in boston with a bang (diabetes and obesity are just a part of this meeting, but a growing part) and the bariatric surgery meeting, which starts in san francisco this tuesday.

So just a word on boston goings - on ... not to be believed, but it looks like the american heart association and the american diabetes association are coming together on the subject of metabolic syndrome. hurrah! we were wondering how long they could stay tied to their opposing views (this is reductive, but basically the ADA was against the use of metabolic syndrome as a descriptor of a specific condition, while the AHA was for it). we always sided with the AHA, simply because doctors don't always have time to spell things out and that as such, some patients will be more driven to act when they hear something a little more dramatic - like being told they have metabolic syndrome - as opposed to JUST understanding (and maybe blowing off) that they have to take a pill for hypertension, a pill for high cholestoral, etc.

Metabolic syndrome (such as it is, with its four different definitions) has also become synonymous with pre-diabetes and we know that name is definitely having an impact on patients - as it, people do NOT want it! now, true, we haven't exactly seen a reduction yet, but we do think people will work harder to get rid of anything with diabetes in the title versus just knowing they have this or that defect (lipids, blood pressure etc) so - while we don't favor treating with fear in isolation (i.e., scaring people with something called metabolic syndrome) we do favor educating people that unless they act in a big way, they'll move quickly from pre-diabetes to diabetes. To boot - obesity is part of most definitions of metabolic syndrome, and anything that prompts PCPs to take out the tape measure and put it around bellys - that's a good thing (you can even do this at home - if you have a waist measure over 30 inches for women or 40 inches for men, that's positive for one symptom of MS - usually you need three to quality...others center on lipids and hypertension).

A debate yesterday at the endocrine meeting "Controversies in Endocrinology: Impact and Management of the Metabolic Syndrome" certainly did make clear that both organizations want to work to reduce conversion of pre-diabetes to diabetes even if there is still disagreement over semantics. the release below basically says that tomorrow there will be a press release from AHA and ADA explaining how they will work together on the metabolic syndrome front. While we don't know exactly what tomorrow's press release from both organization's will bring, we do think that everyone will win, because apparently "cardio-metabolic risk" will become a more official term for both organizations. that probably can't be a bad thing, even if the biggest winner is sanofi!

we agree with Dr. Jay Skyler, who implied in our DCU interview this month (the full interview is posted on our website www.closeconcerns.com) that we should get OVER semantics and just address the problem - we applaud the gist, and hope it happens. in the meantime, we will be watching both the pharmacologic and the surgery fronts with great interest. we believe rimonabant, pramlintide, TZDs, and GLP-1 all will be examined closely in terms of pharmacologic potential and believe that a majority will in time become actual therapies. while the FDA looks to be a very long way from approving anything to treat metabolic syndrome, we would expect to see first a label for pre-diabetes, namely impaired glucose tolerance. of course, then, reimbursement will be the next hurdle! The surgery front (gastric banding to full on surgery) is less clear to us, but given the multi-faceted problem obesity presents, from our perspective, the more solutions, the better. and in terms of surgery, given how much diabetes is downright resolved with surgery, we think reimbursement there is a no-brainer in many cases.

Here's to the multiple winners.... and even though we're not yet sure about rimonabant safety (but still look for FDA approval shortly), good for Sanofi for getting made official this cardiometabolic risk terminology they've now been bandying about for years... (see our November 14 blog from the AHA for more on Sanofi, which we've copied below the Endocrine Society release)

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New Perspective Emerges on Metabolic Syndrome
Sunday June 25, 11:39 am ET
Leaders of the American Diabetes Association and the American Heart Association Announce Joint Letter at ENDO 2006, Annual Meeting of The Endocrine Society

BOSTON, June 25 /PRNewswire/ -- Though they have markedly different opinions on the controversial Metabolic Syndrome, leaders of the American Heart Association and the American Diabetes Association announced at the annual meeting of The Endocrine Society that they will co-publish a statement on Monday expressing a desire for the organizations to work together on the topic of "cardio-metabolic risk."
Despite their differences of opinion, both organizations are working together to prevent heart disease, stroke and diabetes, said Robert H. Eckel, president of the American Heart Association, a physician and professor at the University of Colorado.

Eckel presented alongside John Buse, vice president of the American Diabetes Association in a debate at The Endocrine Society annual meeting entitled "Controversies in Endocrinology: Impact and Management of the Metabolic Syndrome."

The two organizations represented by Buse and Eckel clearly still have differing viewpoints on the Metabolic Syndrome, as articulated last year in a paper published by the American Diabetes Association, "The Metabolic Syndrome: Time for a Critical Appraisal."

The Metabolic Syndrome is loosely defined as a cluster of medical conditions -- including obesity, high blood pressure, high LDL cholesterol (and low HDL) -- that increase the risks of diabetes and cardio-vascular disease.

The American Heart Association, according to Eckel, supports identifying and treating the syndrome through lifestyle modifications and other treatments.

But the American Diabetes Association, Buse said, believes that the definition of the syndrome is poor, and that risk prediction of cardiovascular disease is also poor. Further, he said there is little benefit to treating the syndrome as a whole rather than identifying and treating the various components.

The letter, to be released Monday, uses the term "cardio-metabolic risk," new terminology which Buse said may signify a new way of describing and therefore treating the condition known as Metabolic Syndrome.

The debate also included representatives of the FDA and the pharmaceutical industry.

Founded in 1916, The Endocrine Society is the world's oldest, largest, and most active organization devoted to research on hormones, and the clinical practice of endocrinology. Today, The Endocrine Society's membership consists of over 12,000 scientists, physicians, educators, nurses and students in more than 80 countries. Together, these members represent all basic, applied, and clinical interests in endocrinology. The Endocrine Society is based in Chevy Chase, Maryland. To learn more about the Society, and the field of endocrinology, visit our web site at www.endo-society.org.

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AHA Musings - Drugs and more drugs and more on FIELD

So we keep talking about how cardiology is becoming so much more focused on endocrinology and diabetes ... welllll, that's sort of true, but we believe it's a bit less apt than we had thought, based on a wild search about drugs on the exhibit floor, where we lived the following:

BMS/MERCK:

Kelly: "Hi, are you giving any information about Pargluva here?"
Medical Rep (irritated): "Absolutely not!"

LILLY:

Kelly: "Hi, are you giving any information about Byetta?"
Rep (confused): "By-what?"
Kelly: "Byetta."
Rep (mystified): "By-ate-a?"
Kelly (incredulous): "Yes, Byetta! You know your amazing new drug, the GLP-1?"
Rep (sad): "I don't know about it." (Turning to another rep ... "Do you know about - what is it called? - Byetta?"
Second rep (enthusiastic): "Oh yes! That's doing great! But we don't have it here. That's not our division."
Kelly (questioning): "But aren't cardiologists moving into diabetes? Don't you have a big diabetes division? How can you not have Byetta here?"
First Rep: "Yeah! How can we not have Byetta here? Here, can you fill out this comment card and we'll get you some info .... let me swipe your badge!"
Overweight doctor from Cornell, joining the conversation: "How about Symlin!"
First Rep: "Sim-lin? What's Sim-lin?"
Second Rep: "Sim-lin? What's Sim-lin?"

GLAXO-SMITH-KLEIN:
Kelly: "Hi, are you giving any information about Avandia here?"
Rep (on it): "YES! Please go see this film and then I'll answer all your questions! This is a very important area for us."
There is a film, starting Della Reese and some of her friends with names like Fred and Millie. This is sort of well done, not on the Sanofi scale (see below), but they have a new little song "Get Rosi on board..." It has a nice ring to it and I might find myself singing it to Coco if I'm not careful. The whole film is brilliant at giving data that isn't WRONG exactly, but also isn't footnoted, and if it were, wouldn't be sourced from, say, a NEJM published study. There are statements from the narrator like "In another study, there was an A1C drop of 1.5%, in patients with A1Cs of 9% or higher. Then in another study, there was an A1C drop of 3%, where the baseline was 11.5% - dropouts were high, but it's much better to go on Avandia than up-titrate Metformin! 50% of patients got to goal! Yes, adding Avandia works on core defects - lowering insulin resistance and improving beta cell function ... "

After the film (which was packed for all three times I watched it), the reps came back, offered coffee commuter cups (with red "get Rosie on board" labels), and $30 coupons for a program called "I Can.." (see www.avandia.com - they are taking the DTC pretty seriously.) To top it off, they gave away Hershey's kisses. I took 10 and ate them on the spot, shooting up Symlin as I went .. "What's that?" the rep asked ...

Maybe it's just me, but it really seems like in a little bit here, we're going to start hearing a LOT about TZDs and prevention of diabetes. They are just gearing up...

ABBOTT: I went here before FIELD was announced (see previous post). They were happy and nice and told me FIELD slides would be up November 17 at www.lipidforum.com. They then offered some excellent espresso and biscotti. I asked them about mixing fenofibrate with a glycemic lowering compound and doing a combo drug ... "are you nuts?!" the rep asked. Score one for Abbott on that basis alone ... we talked about how combo drugs are overrated, how dosing is complex, how if the drug works it is fantastic, but if it doesn't, the doc gets a million calls ... I went by after and dejection abounded. I know it's not as positive as it would've been had it been a positive study, but I think either way, it's got to be good add-on therapy, no?

PFIZER:

Kelly: "Hi, are you giving any information about inhaled insulin?"
Rep: "Go talk to the medical director - we're just reps."
Kelly: "Hi, are you giving any information about inhaled insulin?"
Medical director: "No, we're not really saying much about that."
Kelly: "Do you think it'll be approved soon?"
Medical rep: "Let me show you some data on Lipitor ..."

TAKEDA:
Kelly: "Hi, are you giving any information about Actos?"
Rep: "Why, yes! What can we tell you?"
Kelly: "Is it being used as first-line therapy?"
Rep: "Yes! And for pre-diabetes!"
Kelly: "Really? I hadn't realized that trial had come out yet. What did those results show!?!"
Rep: "Well, the trials aren't completed yet. We do not encourage use for pre-diabetes. But it is being used for that."
Kelly: "The ADA '03 DPP data was really powerful with Troglitazone, showing a 70% reduced progression to diabetes ... compared to much lower for Metformin and lifestyle ..."
Rep: "Yes, and you should see the follow up gestational data ..."
Kelly: "How's the edema and CHF?"
Rep: "Well, patients need to be chosen and followed appropriately ...they are seeing a lot fewer problems like that in pre-diabetes .. they are the younger, relatively healthier patients, of course ... now this drug is great in combo with Metformin ...."
Ironically, the Lilly reps _were_ at the Actos booth, since they co-market it for a bit longer ...

ASTRAZENECA:

Kelly: "Hi, are you giving any information about Galida here?"
Rep: "No."
Kelly: "Nothing you can say about this dual PPAR?"
Rep: "We haven't been talking about dual PPARs much lately ..."
Kelly: "Because of the FD ..."
Rep (interrupting): "Yes. But check out our LDL/HDL ratio with Crestor .... "
The conversation then turned to another discussion of how combination therapy isn't as easy as it looks (dosing, mixes, etc.), which I buy, and then to personalized medicine, and the rep explained there was some kind of research ongoing to figure out which type of patient would actually benefit particularly from diet and exercise, etc - they felt more personalized medicine would revolutionalize lipids. I explained that I thought lipids had been revolutionalized ...."$26 billion category and all..." This rep felt some PCPs were seeing as many as 50-60 patients a day "a factory .. and would you want to be dealing with nausea phone calls....?"

SANOFI:
Kelly: "Hi, are you giving any information about Acomplia here?"
Rep (super nice): "Absolutely! See the booth over there? There's an excellent movie there about endocannabanoid systems. I can't even say it yet! But we're learning! Go ahead and watch it ... then let me know any questions you have! We'd love to help in any way possible."
Kelly: "ohhhh - I'll go watch it! When will Acomplia be approved?"
Rep (super nice): "April 2006 is what they're telling us! Go watch the movie, it's in 3-D, and fantastic! It doesn't have the word Acomplia in it, but it'll teach you a lot..."
Kelly: "OK thanks! oh and one other thing, how's Lantus doing?"
Rep: "Fantastic. We love selling this drug - it really changes people's lives."
Kelly: "Mm.. how do you think Levemir will do?"
Rep: "Oh please! Levemir is a glorified NPH!!!"

So I made my way over to the movie, "Exploring the ECS," which WAS in fast, fantastic. These guys don't skip a beat. Sanofi really knows how to market - even at 9 am, there were scads of people lined up grabbing at the 3-D glasses. The film (I can't believe I'm calling it that) was quite educational, and used lots of phrases like "appears to play a role" "seems to be linked" "apparently meaningful" etc. It reminds me of Wall Street days. Hedging is an excellent sport.

But, again, this was very well done ... it reviewed how a "newly discovered" physiologic system, the ECS (endocannabinoid system) plays a key role (see?) in glucose metabolism, lipid metabolism, and insulin resistance. CB1 receptors are found through the body - say, GI tract, brain, adipose tissue and skeletal muscle, for example, and they affect many processes. In the liver, CB1 activity is apparently associated with development of adiposity, dyslipidemia, and insulin resistance - all bad. In the brain, central CB1 activation influences feeding behavior and energy balance. This means satiety ... I really respect now anything that plays on satiety. I used to think it was sort of made up, but boy does Symlin work on satiety - almost sneakily, like I don't really notice it, but then I do ("wow I've eaten half my bacon cheeseburger and I'm not that hungry suddenly..."). I respect satiety, so it'll be interesting to see if that works with this drug.

Then, in adipose tissue, it is said, CB1 activation "appears to stimulate" lipogenesis and to inhibit adiponectin expression. What does adiponectin expression mean? Wellll, so as I understand it, adipose tissue used to be viewed as inert, but now it's seen as an active organ. Low adiponectin levels are commonly found in diabetics and those that are obese. Got it ... that's all we need to know, right ... CB1 activation is bad and adiponectin is good and there isn't enough adiponectin going on ... so we should be wary at the very least of adiponectin inhibition. Low levels of adiponectin, I then learned, are associated with high free fatty acids (FFA), low HDL, high triglycerides, and AND insulin resistance. In skeletal muscle, CB1 activity is associated GI motility and safety signalling. I have to check this out with all my smart connections in pharma, but this gives you an idea how the story is forming ...

I started remembering right about then how excited I got about this drug at ADA - doesn't it seem like, IF safety is established (the CNS questions are big) and for those that can get over side effects, that this should be mixed with Byetta? Byetta has all the glucose pieces that this doesn't have plus Byetta doesn't have insulin resistance and this doesn't have beta cell regeneration ... could be a mix, no? (We know Byetta doesn't necessarily have beta cell preservation or regeneration either - that is yet to be proven. We also are excited about Byetta with TZDs, which seems also complimentary - insulin resistance, potential beta cell regeneration from both, weight loss from Byetta offsetting weight gain from TZDs, potentially lower edema/CHF from combo due to lower dose TZD, etc.)

BMS/MERCK (second lap):

Kelly: "Hi, are you giving any information about Pargluva here?"
Rep: "Pargluva? We don't have a drug called Pargluva." (editor's note - kind of amazing, in hindsight...)

NOVARTIS:
Kelly: "Hi, are you giving any information about LAF-237 here?"
Rep (cold): "No."
Kelly: "Hmm. How about Vildagliptin?"
Rep: "No, we're not talking about that one either."
Kelly: "Anything in diabetes?"
Rep: "No. This is a cardiology meeting!"

And on that note ....

New York Times weighs in on new diabetes medicine ~ a billion isn't so hard to reach!

For those who haven't read it yet, the most-emailed article on the New York Times website yesterday was titled "4 Diabetes Drugs Are Seen Raising Hope and Profit" by Alex Berenson. Written from an analyst's point of view, it talks about Byetta, Exubera, Januvia, and Galvus. Byetta is already on market and Exubera will be released next month. The other two are pending FDA approval.

Diabetes drugs are currently at ~ $15 billion in worldwide annual sales and the article notes that some analysts anticipate this will see a $10 billion increase to $25 billion by 2011 because of increasing numbers of patients being diagnosed with the disease every year (see our June 23 blog on rising type 2 incidence). With these numbers, the NYT says, there's plenty of market share for effective new therapies and Berenson reports that analysts believe all four will become blockbuster drugs with more than $1 billion in sales.

Byetta (exenatide), an incretin mimetic, is clearly the favorite of the moment because it is the first major drug that lowers both HbA1c and weight - a fact that has generated fervent support from the patients and physicians who have used it since its release in May, 2005. For us, the question isn't whether it will reach $1 billion - that's a foregone conclusion - but exactly how many billions it might generate in sales by 2011. If LAR is approved, the answer is certainly multi-billion - and if LAR for some reason is not approved - we still think the answer is multi-billion, but perhaps just not as many as fast.

Of the other three drugs, Exubera is the most commercially uncertain. Developed by Pfizer and approved by the FDA in January, it is the long-anticipated inhaled form of insulin intended for patients not at their glcyemic target who currently avoid insulin because they don't like injections. Although the safety data was deemed sufficient by an FDA panel last year, some researchers still have questions and certainly advise against its use in patients with pulmonary disorders. Any possible safety issues aside, many have focused on the size of the inhaler as a deterrent. We think that is probably overused as an excuse - if people want to take it, they'll get over the size of the inhaler, which will certainly shrink over time, anyway. Reimbursement for us is the main (maybe the only) question right now -- if it isn't paid for, most patients won't want it.   Whether insurers will reimburse for a more expensive insulin that has no new physiological benefits remains an open question.

Novartis' Galvus (vildagliptin) and Merck's Januvia (sitagliptin) are DPP-4 inhibitors (now known as gliptins) that increase glucose sensitivity. Gliptins have less dramatic HbA1c lowering effects than would be ideal, but even so their tolerability and weight neutrality may result in recommendations for them as replacements for existing first- and second- and third-line therapies like sulfonylureas and TZDs - TZDs, of course, are now a $4 billion global market and SFUs commanded in the billions before going generic. There are significant side effects with both, including weight gain and other difficulties (edema, GI problems, etc) and it will be interesting to watch, in fact, whether SFUs even survive.

For more detailed information about all of these drugs, check out our latest DCU issue with our ADA download! In it we report on what we learned about these drugs at the conference, with a heavy focus on incretins in particular.

Incidence of type 2 doubled from 1970s to 1990s per June 2006 circulation

Fox CS, Pencina MJ, Meigs JB, Vasan RS, Levitzky YS, DAgostino RB. "Trends in the Incidence of Type 2 Diabetes Mellitus From the 1970s to the 1990s." Circulation, June 27, 2006. 113(25):2914-2918.

The June 27, 2006 issue of Circulation, the journal of the American Heart Association, includes a report by Fox et al. showing that the incidence of type 2 diabetes in the United States has doubled from the 1970s to the 1990s. This research study used data from the Framingham Heart Study and is significant because it addresses the rates of diabetes incidence (the number people who are newly diagnosed with diabetes) rather than just prevalence (the total number of people who have it). You might say, geez, the 1990s - that was forever ago and we already knew that. Well, yes. But read on!

Background

The original cohort of the Framingham Heart Study was recruited in 1948 for a long term study of the factors that contribute to cardiovascular disease. An Offspring Study, including 5,124 of the original cohort's spouses and offspring, was launched in 1971.

Methodology

In this paper, Dr. Caroline Fox used participants from the offspring cohort who were free of diabetes when they were examined by a physician during one of three examination cycles: 1971 to 1975, 1979 to 1983, and/or 1987 to 1991. Each of these cycles represents the 1970s, 1980s or 1990s. The incidence of diabetes in each decade was defined as the number of participants who developed diabetes within eight years of their initial examination. Confusingly, participants from earlier examination cycles remained in later cycles as long as they didn't develop diabetes in the interim, so there is some overlap in the participants included for each decade. We're not entirely comfortable about the integrity of this approach, but fortunately the authors chose to use only data from participants between 40 and 55 yr old, so despite any double-counting the participants of each examination cycle had similar demographics.

Participants

There were about 700 men and 700 women in each examination cycle. All groups had mean age of 47 yr. Each female group had mean BMI of about 25.5 and each male group had BMI of about 27.5. There was no statistically significant rise in BMI across the three decades. As result of the double-counting mentioned above, only 3,104 unique individuals contributed to the 4,523 total participants included in the three examination cycles. Diabetes was defined as a fasting plasma glucose ≥ 7.0 mmol/L or the use of insulin or a glucose-lowering drug. People with type 1 diabetes were not included in the study. All participants were interviewed at two- or four-year intervals after their initial examination.

Results

Without double counting, a total of 69 out of 1,587 women and 93 out of 1,517 men developed diabetes during the course of the study. For women the eight-year incidence of diabetes was 2.0% in the 1970s, 3.0% in the 1980s, and finally 3.7% in the 1990s. For men the eight-year incidence of diabetes was 2.7% in the 1970s, 3.6% in the 1980s, and finally 5.8% in the 1990s. Overall, there was a 40% increase in diabetes incidence from the 1970s to the 1980s and a 100% increase from the 1980s to the 1990s. There was no significant difference between the sexes in the increase of diabetes incidence.

Interesting Conclusions

When the authors adjusted their data for BMI, they found an interesting trend: though the incidence of diabetes increased slightly in normal and overweight participants, increases in these two groups did not reach statistical significance. Rather, most of the overall increase in incidence came from obese participants, for whom incidence rate doubled from 6% to 12% over the three decades. This confirms, as if there were any doubt, that weight has a significant effect on the incidence of diabetes. More work should be done not only to understand why obese individuals are suffering greater increases in diabetes incidence than normal or overweight individuals but to figure out how to help this population. Drugs, surgery ... the works! We'll have our eye out next week in San Francisco as the bariatric surgery meeting comes to town - as many now know, the resolution of diabetes from surgery has been pretty eye-popping, making the ROI of $20,000-plus cost/surgery appear positively sky-high, long term. Obviously, while other factors in addition to weight in the development of type 2 diabetes are important, and while it is key for us to learn what these are if we are to stem the diabetes epidemic in our aging population, just addressing weight alone would be a heck of a start.

Team Type 1 cycles to victory

Speaking of athletes with type 1 diabetes - we're delighted to point out another inspirational example today. Congratulations to Team Type 1, a group of eight cyclists with type 1 diabetes who just finished the 3,043-mile Race Across AMerica (RAAM) early yesterday with what is for the eight-person division a record average speed of 22.36 mph. Their relay-style race began on June 16, 2006 in Oceanside, California and ended in Atlantic City, New Jersey after five days, sixteen hours, and four minutes of nonstop cycling.

Their entry in the race was sponsored by Abbott Diabetes Care in a campaign to raise $1 million for the Juvenile Diabetes Research Foundation's research to find a cure for type 1 diabetes. But just as meaningful is how their amazing performance in the race has once again highlighted how the limitations of the disease can be overcome through careful blood sugar management. The three goals that Team Type 1 listed on their website, www.teamtype1.org, were to:

1) Win the corporate division of the Race Across AMerica (RAAM)

2) Raise awareness of the need for HbA1c < 6.5, and

3) Show that with regular exercise and good blood glucose control all people with diabetes can live a healthy and fulfilling life.

We'd say that they've unequivocally achieved these goals after their spectacular success in the race. For more about Team Type 1 and RAAM, including an updated photo blog of the race, check out the team's website. Now it's up to all of us to continue working towards not only raising awareness of the need for blood glucose control, but to achieve healthy HbA1c's in the entire diabetes community. Cycle on, Team Type 1!

Diabetes and the Seattle Mariners

As baseball season continues, we'd like to tip our hats in congratulation to Brandon Morrow, a powerhouse 21-year-old right-handed starter from the University of California with type 1 diabetes. Morrow recently signed on with the Seattle Mariners as their first pick and the fifth choice overall in this month's major league draft. With a fastball often in the 96-99 mph range, Morrow doesn't let his diabetes get in the way of his athletic performance. At UC Berkeley he came in as one of the 10 semifinalists for the Roger Clemens Award as the nation's top college pitcher. Mariners scouting director Bob Fontaine told reporters that the team was not at all concerned about his diabetes because of his excellent record with managing diabetes in the past. "He was good with our doctors," Fontaine said.

Morrow's exacting diabetes management took time and practice to evolve. In a 2004 article in The Daily Californian, Nick Wilson writes about how Morrow was diagnosed with type 1 diabetes in the senior year of high school. A friend pointed out that the symptoms of the recent off-season malaise he was suffering sounded like the disease. When he went into the hospital to check, his fasting blood-sugar level was measured at a whopping 800 mg/dL. Once on insulin therapy, he quickly returned to the field where he now had to juggle pitching with glucose self-monitoring and multiple other elements of management.

Moving to college baseball was an especial challenge because of the irregular eating schedules of the road, with its midnight fast food stops and high-carbohydrate snacks. After his doctor warned him about big swings in his blood glucose levels in freshman year of college, he began testing himself more frequently and managing his diet more aggressively. Though he was selected in the 40th round of the 2003 draft by the Anaheim Angels, he chose to continue college instead because he wanted to mature his game and learn how to balance playing with blood glucose management. The latter has become easier since he switched from conventional therapy to continuous subcutaneous insulin injection (CSII) therapy with an insulin pump. He also checks his blood sugar frequently, including between innings. The discipline with which he developed his college game has indeed paid off in this month's EXCELLENT draft.

We're deeply impressed by Brandon's story, which shows yet again how well people with diabetes can do who manage the condition aggressively. We wish him the best of luck in his future career with the Seattle Mariners, although we wish he were playing for the Giants...

Stopping the rise in childhood obesity has Arkansas officials smiling

Arkansas’s war against childhood obesity has been hard to swallow for some, but for us – the proof is in the pudding.  We finally have an update on our earlier blog “On Nicholas D. Kristof on ‘Mike Huckabee Lost 110 Pounds. Ask Him How?’”

Inspired by the Arkansas governor, Mike Huckabee who shed 110 pounds after being diagnosed with type 2 diabetes, the state’s health initiative to target childhood obesity has now started to show some effects.  The June 4, 2006 New York Times article entitled “Obesity Letters Having Effect in Arkansas” describes the results of Huckabee’s health campaign.  Two years ago Arkansas schools began sending home report cards to parents with their child’s body-mass index (BMI), a measure for obesity in both adults and children. Many parents found these letters to be inappropriate, and children whose parents started them on diets and fitness programs feel like they’ve gone to “fat camp.” Still, as unhappy as some people are about the obesity letters, even the unhappy parents have taken action to make their overweight children healthier.

Parents have taken their children to the pediatrician, enrolled them in fitness classes, and removed junk food from their families’ diets.  Fifty-seven percent of Arkansas doctors say that at least one parent has brought in their child’s BMI report this past school year.  Wow! This new kind of report card really has parents trying to make positive and healthy changes for their children.

So is the program having any effect on curbing childhood obesity?

The results of the new Arkansas initiative are surprising at first – nothing has changed. The percentage of overweight children has remained at a steady 38 percent over the past year.  Don’t start panicking yet! This effect could be a good thing according to Jim Raczynski, dean of the College of Public Health at the University of Arkansas for Medical Science: "We think probably, since there's been no change, that's probably good news.  We may have stopped the increase."  Since childhood obesity has been on a dramatic rise, especially in the state of Arkansas, a stop in this rise is a fantastic effect.  The state has more work to do given that 38 percent of Arkansas children are still overweight, but halting the increase is certainly something to celebrate.  In fact, the states of California, Florida, and Pennsylvania are tagging along, feeding off Arkansas’ success. Who knows, maybe someday every student’s BMI will be alongside the A’s, B’s, and C’s in his or her report card.

June 4, 2006

Obesity Letters Having Effect in Arkansas

By THE ASSOCIATED PRESS

LITTLE ROCK, Ark., June 3 (AP) — It has been two years since Arkansas schools started sending letters home to parents with students' report cards telling them if their children were overweight.
Plenty of parents were unhappy. But a lot of them did something about it.

There have been more visits to the pediatrician for talks about weight problems. Fitness class attendance is up. Diet pill use by high-schoolers is down.

Other states, including California, Florida and Pennsylvania, have adopted similar programs.

Dr. Karen Young, medical director for the pediatric fitness clinic at Arkansas Children's Hospital, told of a mother upset when she got word from school that her child was overweight. The mother wanted a second opinion from Dr. Young, but in the meantime, she cut sweets from the family diet and slimmed the child down before the appointment.

"Even though she was upset with the letter and felt it was wrong, she still changed the family's lifestyle," Dr. Young said. "A lot of positive things have come out of those letters."
The letters record each child's body-mass index, the same weight-height formula used to calculate adult obesity.

Across the state 57 percent of doctors said they had at least one parent bring in their child's letter from the school for discussion during the last school year.

Dr. Young said she has had more visits from parents seeking help for their entire family.
"I don't care what size their siblings are or their parents, everyone in the family should eat healthy and exercise," she said. "What's good for them is good for everybody."

A local TV news report on Dr. Young's clinic led Marsha Simon-Younger to enroll her 11-year-old daughter Nasirah in fitness classes. Since the girl joined this spring, she has felt better and is eating healthier, her mother said.

"At first, my daughter was really reluctant to go because she thought of it as a fat camp," said Ms. Simon-Younger. But once Nasirah arrived, she saw a friend from church and Girl Scouts and felt at ease.

After the first year, the percentage of overweight schoolchildren remained where it was at the start — 38 percent.

"We think probably, since there's been no change, that's probably good news," said Jim Raczynski, dean of the College of Public Health at the University of Arkansas for Medical Sciences. "We may have stopped the increase."

Amylin and Dex Com - stocks that deserve mention

Kelly and Cindy here. So we really don't write about stocks because that's not our job. That's what we used to do when we worked on Wall Street and god knows there are more than enough people doing that - we don't need more! We certainly write about companies plenty and sometimes people ask about what our disclosures mean. They mean just what they say - we work with many companies in the diabetes industry and we always want readers to understand that, although it never influences our writing. For most companies with whom we do work, we actually don't know anything more than anyone on the street about their businesses, although we've signed NDAs with all and we make it a practice to come not even close to the line.

So, we wanted to get that out of the way. We do work with companies in order to earn a living and go to conferences and get journals and cover overhead. We could stop working with companies, but then we'd have to go back to Wall Street, which we'd never in a million years want to do. We love our jobs!  Some wonder if we are biased, and we think if anything, we're just biased by patient perspective.

We had a couple of thoughts on AMLN and DXCM - even though we typically don't write about stocks, really only about companies, the stock prices of both strike us as cheap. So on AMLN, this one is easy. Thomas Wei of Piper (one of our v favorite analysts to read - whip smart!) discovered yesterday at ADA that doctors would be asked to slow down new Byetta scripts. Anyone who was at ADA knows this is just the eminantly responsible thing for the company to do. If last year's ADA was positive for Byetta, this year's was positively out of control. There's nothing else to say. Everyone had fabulous Byetta stories and most people had incredibly fabulous stories. The company had dozens of opportunities to share brilliance - no fewer than 12 posters, five presentations ...the coup was its company meeting, which was webcast Sunday night and which you can listen to on the company's website. The information shared on Leptin (see our latest DCU for an in depth Leptin piece and interview with key scientist Dr. Jeffrey Friedman of Amylin's SAB) we found truly exciting and we'll be thinking a long time about the next generation amylin. Then, OBESITY - Amylin is on this, even more than we thought, and the company is thinking big. Finally, LAR sounds good but even if you were concerned, Byetta is still an absolute jackpot. Three year open label data showed sustained A1c benefit and more weight loss (and check out the line's downward slop). For all these reasons, we strongly suspect anyone who buys and holds AMLN will do very well over the long term. Short term, for us, investors are highly focused on the wrong things, e.g., cartridge timing and a bevy of thoughts on what else could go wrong. Silly ...! A number of people thanked us at ADA for making money for them on AMLN stock - we demurred, since we don't, as a practice, discuss buying and selling stocks. But, they said, your issue "The Magic Called Byetta," when the stock traded around $15/share, told a different story. Wellllll... okay. Whatever we say, you should put into your own magic mosaic, and see what you think...

On DXCM, we have less to say. The stock has come down a LOT due as far as we can tell to an unfounded rumor (from our perspective) that the company is going to be doing a recall.   We would be shocked if a recall happened since there's nothing dangerous about the product, per se. It's been tested for safety and efficacy and found to work well, given that it's 2006. As we wrote in our newsletter a couple of months ago, we really like the product when it works and we believe the category really has a chance to take off when reimbursement emerges. Not sure when this will happen, but we do see it as a when. In the meantime, the company has done spectacularly well on the valuation front, and that the stock has come down, given that reimbursement won't likely emerge in a big way until 2008, we think is reasonable. This has been a pretty BIG move down, and our guess is that the company will eventually be bought for higher than the stock is now, but for sure it will be volatile. We also think for SURE there will one day be a thriving commercial market for continuous and when that happens - which will take a bit of time - this stock will loook cheap. In the meantime, volatility will prevail, so look left, look right, look left again ...
 

ADA day #5 - parting shots

Today was a fantastic close to the ADA with the clinical and science updates in particular - anything that was mentioned as a highlight by the established luminaries had a warm glow on it instantly as people whispered about the special acknowledgement.

There was some controversy with drug trials and with devices - we'll continue more on this front shortly!

ADA day #4 - early insulin, pro or con? Emotions run high

Debate: Insulin as initial treatment of type 2 diabetes- the way to go?
Pro: Michael Alvarsson MD PhD; Con: Mayer B. Davidson MD

This was an interesting session. Before incretins, it seemed obvious that far more patients need to go on insulin, as evidenced by the poor, poor outcomes - as most who follow diabetes know very well, roughly two third of patients with diabetes are considered to be "out of control." In fact, we believe the estimate is likely on the very low side, since it takes into account only A1c - and only A1c percentages over 7 count, whereas we believe that ADA will eventually put its A1c target closer to AACE and IDF - in fact, once ACCORD results emerge (admittedly not until 2009), we believe the target will move to below 6. This is a controversial topic, what the target should be, but many leading endos now tell patients they should be at 5 or below.

So in this "early insulin - yes or no" session, the Q&A period of the debate revealed the variety of patient populations worldwide and the difficulty in standardizing a treatment.  The subject of insulin as an initial treatment continues to be quite controversial—there was good turnout at the session, a lot of participation, and emotions ran quite high.

*Dr. Alvarsson claimed insulin was easier to intensify once patients were on it, that it might eliminate glucotoxic effects on beta-cells, and that, by the results of his own study, a patient’s quality of life does not appear to be affected by treatment (only complications).  In contrast, Dr. Davidson claimed that early insulin treatment is unnecessary if we can attain glycemic control since his experience shows that a patient’s lifestyle changes very much when he or she is put on insulin and that patients are often too elusive to maintain the frequent contact that insulin treatment requires.

*The issue of diabetes education was therefore a big one.  Insulin treatment is difficult when patients are under-educated and under-supported.  While Dr. Davidson suggested that step treatment could avoid having to teach a patient SMBG, Dr. Irl Hirsch made the comment, to a flurry of applause, that “they need to learn SMBG whether they are going on insulin or not!” THANK YOU! We know ourselves that information prompts engagement, and that patients need to know where they are in order to figure out where they are going. The idea that SMBG can be skipped is absurd to us. Even if patients aren't on insulin, SMBG can still be quite helpful in figuring out the impact of various foods, the glycemic index of these foods, the impact of exercise, etc.

*Those who agreed with Dr. Davidson that insulin should be delayed were treating similar populations—poor and predominantly Hispanic.  A doctor from south Texas said his patients couldn’t afford needles, so simply used diet and pills.  In our view, that's a very different - and more important - problem -- reimbursement for basic diabetes supplies. Urging patients to forego treatment isn't a great answer for that. A nurse treating this population reminded people that some people cannot count and that “we have to be realistic.”  Dr. Alvarsson admitted that in Sweden, the government pays for treatment, and a few members of the audience commented that for many Americans, pills are more feasible.  A doctor from New Orleans concluded from experience treating Katrina victims alongside his regular wealthier patients, treatment should be “individualized and non-traditional.” We certainly would support this if the system could handle it - once again, we realize that reimbursement for doctors' time badly needs to be addressed.

*Nevertheless, when the chair of the debate asked the audience how they would treat a walk-in patient who was obese, middle-aged, with T2DM, and a blood glucose level of 400 mg/dl, about 85% raised their hands to insulin and about 15% raised their hands to pills.  At this point, there were cries from Dr. Davidson supporting the 15% of, “See! You’re thinking outside the box!” This was unbelievable, since if someone is running 400 mg/dL, it's hard to believe the A1C was still in the single digits...

*A couple of audience members offered their education services to doctors, reminding people that CDEs are available and should be utilized.  One woman offered the services of CDEs who could travel to wherever they were needed.  Some said the small print was that they were being sponsored by a particular pharmaceutical company and the patients would have to be using one of that firm’s particular products. (Even if this were true, that wouldn't necessarily be the worst thing in the world in our view, since most of the blood glucose monitoring products sold by the big firms are quite good.) Another member of the audience offered his services and suggestively accused this woman of being unethical. WHEW!  The woman subsequently returned to the microphone with a moving and tearful speech about how we need to use whatever resources we have in order to reach out to people and educate them.  We agree.

* On the issue of insulin overall, we expect the companies to continue to run scared - as it is, according CDC data, the percentage of patients in the US going on insulin continues to decline (even if the absolute number continues to rise because of the vast growth of new patients coming into the system every year). The most recent numbers, as of 2004, show about 29% of patients on insulin, compared to 32% in 2002. We believe that the percentage could decline further - dramatically! - in the wake of Byetta. We saw data the other night that showed three-year open label data where the A1c decline of ~1.0 had persisted out to three years - although this responder data, not data that could be generalized, this stat was notable, particularly when considered in combination with the finding that weight continued to decline three years out. Clearly, a new medicine that works so well will contribute to fewer people going on insulin, and ultimately, probably fewer people moving to prandial insulin even when they do go on long-acting insulin.  Not only are people delaying going on insulin, some people are even coming off insulin who go on Byetta, even if this is off-label.

Interesting times. We believe there are other opportunities for insulin companies - such as pursuing insulin intensification in hospitals (especially patients who are able to leave the hospital), an opportunities that obviously hasn't escaped them. In the scheme of traditional type 2 treatments, however, patients will continue to have more alternatives, which we applaud, since the main goal, no matter what anyone is selling, is improved outcomes, both short- and long-term.