The Business of Diabetes: Lilly Presents An Otimistic 2008 Forecast; Wall Street Less Certain

Yesterday at an investor conference, Eli Lilly and Company (the maker of the insulin analog Humalog, antidepressant Cymbalta, erectile dysfunction treatment Cialis and co-marketer of the type 2 diabetes drug Byetta) executives projected 2008 earnings per share between $3.85 and $4 on sales growth in the mid-to-high single digits.

According to analysts surveyed by Thomson Financial as well as Reuters' estimates, that forecast translates to growth of 8% to 14% over the expected 2007 full-year earnings, which exceeds analysts' 2008 profit forecast of $3.81 a share.

Recently, the company has tried its best to put a positive spin on the results for its anti blood clotting drug prasugrel, which, assuming it receives FDA approval, will compete with the blockbuster Plavix, which is jointly marketed by Bristol-Myers Squibb and Sanofi Aventis. But news that the company was halting a trial due to patient safety concerns raised questions about whether this drug would be a sure-fire blockbuster in the making, or whether the company was simply engaging in damage control.

As I wrote fairly recently, CEO Sidney Taurel wrote a scathing letter published in The Wall Street Journal about integrity in the media, but the irony was that his letter sounded, at beast hippocritical, more like a CEO who wanted to protect the value of his stock options than a company truly concerned about patient well-bring. With the company's latest forecast, the real question is whether anyone on Wall Street believes it.

"Clearly the 2008 forecast is much better than expected," said Lehman Brothers analyst Tony Butler.

A fair number of prominent Wall Street analysts have questioned whether the company will have enough new products to make up for the expected plunge in sales of several drugs that will lose their American patent protection in coming years. These drugs include the chemotherapy agent Gemzar in 2010, Zyprexa in 2011 and Cymbalta in 2013.

Citigroup Smith Barney noted "Lilly is including a timely approval of prasugrel in its assumptions, which could prove to be optimistic given the mixed TRITON study results. That said, even excluding a prasugrel launch, the guidance was above our expectations." This opinion was shared by many, including the few who remain bullish on the stock.

S&P said "we think long-term prospects hinge heavily on prasugrel, which has shown mixed clinical data (good efficacy, but with bleeding risks), to offset a patent cliff in 2010-2013."

That time period is a huge concern to analysts. Morgan Stanley analyst Jami Rubin echoed that outlook, saying "The issue is not 2008; the issue is 2011 and beyond."

Overall, Wall Street is presently evenly split when it comes to its outlook for Lilly. Zacks data shows that Lilly has earned 4 "strong buy," 11 "hold," and 3 "strong sell" ratings. This configuration leaves the shares vulnerable to both upgrades and downgrades.

Smith Barney, which is recommending its clients "hold" the stock, rated Lilly as Medium Risk, largely because of challenges to its in-line product portfolio (specifically Zyprexa, the insulin franchise, and Evista). They note that there are a number of downside risks to their target price.

Lilly was quite bullish on the outlook for its diabetes business, but a closer look suggests that outlook is not due to excellent fundamentals in the business, but due to some good luck. For one thing, the diabetes market is growing rapidly on a worldwide basis, so almost everyone will show some growth, even if they do nothing. But Lilly's diabetes drug outlook is heavily dependent on foreign sales, and it may be relatively easy to accomplish revenue growth in spite of severe weakness in its product line thanks to expected continued weakness in the U.S. dollar.

Drugs sold in other countries are paid for in the local currency while Lilly's costs are indexed to the dollar, so they benefit by converting those Canadian Dollars, Japanese Yen or Euros into U.S. Dollars. But the fundamentals look less solid.

In the U.S., Lilly's insulin business is likely to continue struggling. As The Wall Street Journal's Health Blog recently reported, the rivalry between Novo and Lilly means that while many drug sales reps are getting pink slips, both companies have instead been beefing their salesforces for diabetes products, although as The Wall Street Journal reported, Lilly has been using contract sales representatives rather than its own employees to sell its diabetes drugs. However, the other side to the currency exchange equation is that rival Novo Nordisk can hire more American salespeople while having a much smaller impact on its bottom line because their earnings are expressed in Danish Krones. It will be tougher for Lilly to absorb those costs, so it was not at all surprising that Lilly president John Lechleiter said that the company had no plans at the moment to hire even more diabetes reps, saying "We're not in this to see who can add more salespeople."

But Lilly also faces trouble from another European rival, France's Sanofi Aventis. Their rapid-acting insulin analog, Apidra (which is a relative newcomer), is very likely to take some share from both Humalog and Novolog because those are the two best sellers, and Apidra's market share is likely to continue growing, admittedly from a small base.

Finally, although the brand-name drug industry was able to postpone a vote on a bill in 2007 impacting biopharmaceuticals, it seems almost certain that in 2008, Congress will pass legislation enabling generic biopharmaceuticals (see here for my article on that subject, including links to many follow-ups). Even Novo Nordisk's U.S. President, Martin Soeters, told Reuters that his company fully expects generics to emerge by 2008 or 2009 at the latest. That means Lilly's venerable yet highly profitable Humulin business could face serious risks from generics in the not-too-distant future, and Humulin still accounts for about 25% of the company's diabetes business revenues.

The real question is whether Lilly's drug pipeline is all that much stronger than its rivals. In the words of The Wall Street Journal, at the moment "Big Pharma Faces Grim Prognosis". The rise of generics wouldn't matter quite as much if the drug companies research labs were creating a stream of new hits, but they aren't. Wall Street analysts examine the drug pipeline's thoroughly when making their forecasts, as do money managers such as pension funds and mutual fund companies who own the stocks.

On Friday morning, following the Lilly investor presentation, Lilly shares were little changed despite the company's rosy 2008 forecast. It seems that so far, investors remain unconvinced.

Arthur Frommer on Blogging

Contrary to the impression that I give with my blog, I do have a full life outside of diabetes, its just that has never been the focus of my blog postings. After all, I don't think people read here for details on how I spent my weekend (at least I hope not)! But every once and a while, I have some personal detail that is worth sharing.

On Tuesday night, I had the opportunity to meet Arthur Frommer, whose name is synonymous with travel since he first published his groundbreaking book "Europe on $5 a Day" back in the 1950's. He was giving a presentation to NYU alumni, although it was open to anyone who wanted to attend. Mr. Frommer has been hailed as "the dean of budget travel", and unlike the authors of some other travel book series, he actually stays at the lodgings that are recommended in his publications. The "Dollar A Day" series has since been retired, and in its place, a new series bearing the name of his daughter (Pauline Frommer) has emerged. Pauline, who co-authored The New World of Travel with her father, has authored a number of the books herself, and edited the ones she hasn't written personally.

I have long admired Mr. Frommer's work (although I preferred the books he personally authored much moreso than those done under the "Frommer's" brand name but written by others), particularly because I share so many of his views on the world. Self-described as "A devout liberal Democrat in the FDR tradition" he refuses to visit countries under occupation or military rule. Thats one reason some countries he once recommended, like Venezuela (which could re-emerge given this week's election results) and Thailand, have since been excluded from his recommended places to visit. He is also very opinionated, and occasionally, brutally frank about it -- one reason I like him as a travel writer! For example, Arthur Frommer's Branson, a travel guide he assigned to and wrote himself because of his Missouri boyhood. While he initially thought he would enjoy writing a book that celebrated the city's enterprise, instead, he was disappointed by what he saw, which was reflected (to some extent, anyway) in the book. Here's what he told the press about his Branson experience:

"I hated the jingoism. I hated these country singers, who had all been draft dodgers themselves during Vietnam, who marched down the aisle with drum beats, with machine-gun bullets, and waved the flag," he says, still disgusted. "Also, all of these people who became so religious! ... Many of the country-music theaters in Branson are used as stages for proselytizing." (Editor note: Gospel concerts are not necessarily the same as country concerts.)

Not everyone shares his political outlook or his perspective, but that doesn't mean they won't find his books valuable. In his own words, "Travel is scarcely worth the effort unless it is associated with people, learning and ideas." With the exception of The New World of Travel, Frommer's books generally stick to the basics, how to get there, get around, where to stay, where to eat, what the attractions are, etc., and those are usually routine without having an injection of too much personal opinion.

So, my readers may be wondering, what does this have to do with diabetes? The answer is nothing, but it does have to do with blogging, thus the reason I am sharing it today.

Arthur Frommer On Blogging

I asked Mr. Frommer to autograph my copy of The New World of Travel, which I consider to be one of his best publications ever. He naturally obliged, and when doing so, he commented "Gee, we really need to update this book" (the latest edition was last updated in 1996-1997), as he noted, some of the operators noted in the book had moved, been acquired, gone out of business, etc., although he acknowledged that the basic idea behind the book had changed very little, and that much remained as valid today as they did back when the book was first published in 1988.

I responded by noting, "There's always your blog!" He laughed, and said "I have really created a monster with the blog!", noting that he often feels compelled to make much more than 2 posts a day. (In fact, it is not uncommon for there to be 5 more more posts each day. Although not all are authored by him, those that bear his name are, and generally outnumber those that do not.) He mentioned that last year, there were over 800 postings in his blog. I said that no one expected him to have more than 1 posting a day, which he responded to by laughing.

Although I met him personally for only a few minutes, the time I did spend was quite valuable, and many of my questions were answered before I even asked them. In all, it was a valuable meeting.

Carb Management Good for Everyone, FDA Budget & Organization Issues

First, people with diabetes are regularly told that they should try to manage their consumption of carbohydrates, particularly highly-refined carbs like sugar, refined white flour, potatoes, rice and other foods that cause a rapid rise in blood glucose levels. The reasons differ, depending on what type of diabetes a person has. In the case of type 1, the non-physiological manner in which insulin is administered means that insulin is delayed in getting into the bloodstream and therefore cannot adequately match the body's needs. Although insulin analogs are supposed to better address this issue, they are not without their flaws. People with type 2 who use supplemental insulins have similar issues to people with type 1. They, along with those on other treatments also try to manage their carb intake to avoid spikes so the insulin already present in their bodies can work effectively with any other treatments they are using. Based on decades of experience, I certainly would never dispute the recommendation to manage carb consumption, because it has proven its value repeatedly.

However, I always have a sense of irritation when people without diabetes feel free to consume entire bagels (which are carb bombs, for a lack of a better term), and then wash it down with a sugary carton of orange (or grapefruit, apple, etc.) or a mocha frappucino and believe they don't have to worry about it because they don't have diabetes. It turns out that managing carb consumption applies to everyone, not just people with diabetes.

Whenever simple carbs are consumed, the body is forced to respond by releasing a surge of insulin to counteract the rapid rise in blood glucose caused by those foods. As a wise person once wrote (and I paraphrase here because I cannot find the original work), rapidly forcing glucose into the cells goes against the body's natural order of things, and this applies whether or not a person has diabetes. Many people without diabetes have reactive hypoglycemia caused by the insulin surge that the carb consumption causes. This may create a temporary sense of discomfort, but should also be a warning sign that what they're doing is not the best thing for their body or health.

Now, Researchers led by Chung-Jung Chiu and Allen Taylor, both at the Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) in Boston, MA analyzed dietary intake and other data from more than 4,000 men and women aged 55 to 80 participating in the Age-Related Eye Disease Study, or AREDS. They found that consuming higher-than-average amounts of carbohydrates that cause blood sugar levels to spike and fall rapidly may be a risk factor for central vision loss with aging, which has nothing to do with diabetes, but does have to do with vision loss in the elderly. Although the findings are preliminary, they do suggest that the modern diet simply doesn't work as well as more traditional diets based largely on unprocessed foods.

See here for a summary of those findings: http://www.sciencedaily.com/releases/2007/11/071126153729.htm

Advisers Say F.D.A.'s Flaws Put Lives at Risk

Second, and perhaps more important, as the major news media reported, the U.S. Food and Drug Administration (FDA) is desperately short of money and poorly organized, which is putting people's lives at risk. The report was written by three members of the F.D.A. Science Board, an advisory panel that reports directly to the agency's commissioner, Dr. Andrew C. von Eschenbach. The three authors in turn had 30 scientific advisers.

Among the problems cited in the report were inadequate staffing, poor retention, out-of-date technology and a lack of resources, all of which have impaired the FDA's abilities. The report was a result of a year-long review by a distinguished panel of experts, the Subcommittee's report concludes that the state of FDA's scientific and regulatory programs could not be separated from the lack of resources available to support the agency's scientific base, hire and train a broadly-capable scientific workforce, and build a sophisticated and modern information technology infrastructure.

The full report, entitled "FDA Science and Mission at Risk", can be found at the Food and Drug Administration's website.

"Over the last decade, complex scientific advances, globalization and challenging new safety issues have combined to multiply the responsibilities of the FDA. As this new report makes clear: our expectations cannot exceed the resources we give FDA to accomplish its mission. In this regard, more is definitely better," commented Mark McClellan, MD, former FDA commissioner and chairman of the new Reagan-Udall Institute designed to enhance FDA's readiness for future scientific challenges.

But while Congress passed more than 100 laws expanding the FDA's authority since 1988, it has not increased the funding appropriately, the report found. As The New York Times reported, "the report concludes that over the last two decades, the agency's public health responsibilities have soared while its appropriations have barely budged. The result is that the FDA is falling farther and farther behind in carrying out its responsibilities and understanding the science it needs to do its many jobs." In fact, during the same 20-year period, while faced with 123 new statutes, FDA gained through appropriation only 646 employees - an increase of 9% - and lost more than $300 million to inflation.

To give just one example of how the agency's computer system has failed the public health, the report notes that "most recently during an E. coli food contamination investigation" the agency's aging computer system was prone to breakdowns.

"Reports of product dangers are not rapidly compared and analyzed, inspectors' reports are still handwritten and slow to work their way through the compliance system, and the system for managing imported products cannot communicate with customs and other government systems," the report stated.

In addition, the FDA often misses significant product arrivals because its computers are so poor that they cannot distinguish between shipments of road salt and those of table salt, the report said.

Don Kennedy, PhD, former FDA commissioner and editor-in-chief of the scientific journal Science said that the "FDA can't improve its science, prepare for the future, or protect American consumers without significant additional resources. Congress is negotiating FDA's FY 2008 (current year) budget right now and can start to fix this critical problem."

The current problem is caused, in part, by the major funding mechanism for the FDA at the present time. As the Boston Globe reported:

In 1992, Congress put the fox in the chicken coop. It passed the Prescription Drug User Fee Act, which authorizes drug companies to pay "user fees" to the FDA for each brand-name drug considered for approval. Nearly all of the money generated by these fees has been earmarked to speed up the approval process.

In effect, the user fee act put the FDA on the payroll of the industry it regulates. Last year, the fees came to about $300 million, which the companies recoup many times over by getting their drugs to market faster.

But while it's a small investment for drug companies, it's a lot of money for the agency, and it has drastically changed the way it operates -- creating a disproportionate emphasis on approving brand-name drugs in a hurry. Consequently, the part of the agency that reviews new drugs gets more than half its money from user fees, and it has grown rapidly. Meanwhile, the parts that monitor safety, ensure manufacturing standards, and check ads for accuracy have languished or even shrunk.

Obviously, the President and Congress shares the blame for this situation, but it remains to be seen as to how they address it. The user fee system has enabled the U.S. Government to largely avoid paying for the agency which is responsible for the safety of the U.S. food and drug supply. With their focus fixated on a failed policy in Iraq and a desire to cut taxes (for certain groups, anyway), Congress had planned to simply re-authorize the user-fee system and the President promised to rubber-stamp approve it as long as restrictions on the Pentagon's budget were not included.

But the moral to the story is that if we want the food and drug supply to be safe, then taxpayers need to pay for it, otherwise we have no one to blame but ourselves. Perhaps this report will help change some minds among lawmakers.

No Dumb Diabetes Research Awards for 2007

In the past around this time of year, I had people vote for the "Dumbest Diabetes Research of the Year". I will not be doing that in 2007, in part, because I did not do much as far as tracking the mindless studies done in the name of diabetes research this year. I must apologize if anyone was hoping to vote, but I would have to spend a lot of time sifting through medical journals, and at this time of year, that really isn't my priority right now. But I'd love to collect your nominations!

As you may recall, last year, the winning study was an article entitled "Short legs related to excess weight and diabetes" in which researchers from Johns Hopkins University conducted a cross-sectional analysis of 7,424 adults aged 40–74 years, from the third National Health and Nutrition Examination Survey (NHANES) and concluded that being short - specifically having short legs and a low leg length-to-height ratio - was linked to an increased type 2 diabetes and obesity risk in middle age. They recommended "early intervention" to improve childhood nutrition in diabetes prevention. While this was a meta analysis, the study suggested that the parents are to blame for adults getting type 2 diabetes, which may be a flawed conclusion. Other studies examined, if you can believe it, the effect of chili consumption on glycemic control. Gimme a break!

Each year, including 2007, millions of dollars are indeed wasted on such mindless research, rather than investigating flaws in current treatments, or looking at issues that are important to patients. As my post last week noted, most studies undertaken ignore everything but glycemic control, and an article published in The Lancet calls into question whether the medical profession needs to re-examine the issues that clinical trials actually investigate, because there is more to managing diabetes than simply controlling blood sugars, its just that researchers seem blinded to that fact.

More troubling is the not-so-subtle implication that results from a non-scientific sample are applicable to all patients with diabetes, which is not only inappropriate, but helps perpetuate myths about diabetes to an already ignorant population.

Last week, Reuters did a story with a headline declaring that people with diabetes routinely make unsafe driving decisions, specifically claiming that patients drive automobiles while their blood glucose levels are hypoglycemic.

Unfortunately, the study, which was done in the Netherlands, was conducted on just 65 people, and the number of people who behaved in the risky manner was a mere 21 people, which is hardly sufficient to declare millions of people worldwide (including many with type 2 who are less prone to hypoglycemia because they have fully functional counterregulatory systems, which are impaired in people with type 1) as routinely engaging in unsafe behavior. Yet the headlines suggest guilt by association. Lilly's Sidney Taurel may gripe about the media not being objective in its coverage, and this may not be exactly what he had in mind, but there is some truth to that assertion.

Regardless, I would encourage everyone to read the details before succumbing to the media's declarations that damn the entire Diabetes OC Community, whether it is engaging in risky driving behavior, or of having a "lifestyle" disease caused, according to the media's description, by sloth.

Mr. Taurel is right that the media needs to do better, but not just to benefit Eli Lilly and Company shareholders, but to ensure people are not given sound bytes of mis-information about diabetes.

Most Diabetes Clinical Trials Ignore Everything But Blood Sugar Control

For those of you who read Diabetes Health, you may have caught a recent write-up that indicated a commentary article published in the September 29, 2007 edition of The Lancet entitled "Patient-important outcomes in diabetes—time for consensus" in which the authors, largely from the Mayo Clinic, report that a majority of diabetes clinical trials in the U.S. ignore virtually everything except glycemic control. In the article, the authors wrote:

"Unfortunately, HbA1c loses its validity as a surrogate marker when patients have a constellation of metabolic abnormalities, when the most common complications are macrovascular, and when the treatments have multiple poorly understood effects."

Obviously, that was a not-so-subtle reference recent issues with the GlaxoSmithKline drug Avandia. Unfortunately, the reason for this is driven largely by the U.S. Food and Drug Administration (FDA) and other drug regulatory agencies, which really consider nothing else except glycemic control when evaluating new diabetes treatments. But the same applies to type 1 diabetes treatments, too.

For example, Dr. Steven Edelman, assistant professor of medicine at the University of California San Diego School of Medicine, wrote to the FDA in 2003 in support of Symlin's New Drug Application, "Our country has tunnel vision in that a drug is judged on its ability to drop the A1c and is blinded to the many other important aspects that a therapeutic agent for diabetes can offer."

Even if a patient's A1c doesn't shift, most diabetes medicines (including insulin) still have major problems that impact patients' overall quality of life as well as compliance, including unpredictable glucose swings throughout the day, hypoglycemia, weight gain, gastrointestinal issues, and general frustration with the lack of precision in trying to actually control their blood glucose levels.

At least now we have credible, peer-reviewed data to quantify just how widespread this problem actually is, which happened to be published in the world's oldest peer-reviewed medical journal. According to the Mayo Clinic, only 1 in 5 trials measures the effect of drugs on quality of life and risk of complications. As Diabetes Health summarized, "The trials can be smaller, shorter, and cheaper without considering these factors, but they're not necessarily better for patients."

According to the commentary by Victor Montori, MD, of the Mayo Clinic, "the apparent benefits of these trials are a mirage….Patients and society may end up paying dearly for medications that cause more harm than good…. The medical community should insist that we invest the resources needed to do trials that ascertain the effect of interventions on patient-important outcomes."

The commentary concluded: "A conscientious patient with diabetes would like to choose drugs that maximize benefit (reduce complications) and minimize burden (route of administration, need for self-monitoring, cost), side-effects (weight gain), and efficacy failure (hypoglycemia)."

I happened to find a copy of The Lancet article on the Internet (normally, they charge $30) so you may access the Lancet commentary, including a truly lovely photograph of a foot ulcer here. Happy reading!

Note to Sidney Taurel: Don't Expect Us to Cry You a River

This morning's Wall Street Journal featured an interesting opinion piece written by Sidney Taurel, who is the chairman and CEO of Eli Lilly and Company. See below for details. My previous letter written to him can be seen here.

In his commentary, Mr. Taurel argues that a lot of pharma reporting in the media is misinformation, or perhaps what could best be called sensationalism. While I agree with that general assessment, Mr. Taurel may find the reasons for my agreement a bit more disturbing.

First, lets look at the big picture. Since 1997, when the Food and Drug Administration (FDA) loosened the restrictions on what is called direct-to-consumer (DTC) advertising, drug companies have spent billions of dollars advertising their drugs to a general audience. Amy Tenderich recently wrote "direct-to-consumer (DTC) advertising 'glamorizes and normalizes the use of prescription medication.'"

Apparently, what Mr. Taurel refers to as "the media beast" which he claims needs to be fed copy, is not above using the media, or even manipulating the media to push drugs like Cialis for erectile dysfunction (have you seen any Cialis commercials when watching the NFL lately?). Lilly is hardly alone in this, so they can't really be singled out for the practice -- its arguably necessary to compete in this segment.

To be completely fair, consumers aren't stupid, and they are easily able to distinguish paid advertisements from other media programming. But more subtle manipulation of the media is also apparently fair game, and Lilly is a master of that. But isn't complaining about the same media you feel completely free to manipulate to your company's benefit a tad hypocritical? Like anything, you cannot have the good without also having the bad, otherwise those two terms have no meaning whatsoever.

But I am more troubled by what seems to be a bit of bitterness by Mr. Taurel when the company's stock price is suddenly hit, then all of a suddenly company is concerned about truth in media. Perhaps Mr. Taurel is getting ready to retire and the value of his stock options fell as a result of the latest incident.

But as a Lilly shareholder, I feel company management has violated their fiduciary responsibility to us, and that does not make me happy. The insulin business has been ignored for over a decade, and market share trends reflect that. In 2000, the company had 82% of the U.S. market, while in 2006, they had just 43% according to data from IMS Health. This was done as the company poured billions of dollars into treatments for such urgent medical conditions as male impotence while investing hardly anything in the company's area of traditional expertise: type 1 diabetes treatments.

The following is an excerpt from Dr. Arthur Teuscher's recent book (see Forward, p. VII), "Insulin: A Voice For Choice" (also see the Diabetes Health article on it here):



On October 29, 1982, the United States Food and Drug Administration (FDA) approved an application by Eli Lilly and Company of Indianapolis, Ind. to market its new synthesized recombinant DNA insulin. The FDA's 4-month review of this first medical product of biotechnology was remarkably less than the average time for drug reviews in those days, suggesting unusual enthusiasm by the FDA staff for the product. The product's name, also subject to FDA approval, was 'Humulin', a name which contradicted the agency's long-standing regulation disallowing "fanciful"' names or false and/or misleading claims embedded in the name. (As the footnotes indicate, "An example of an intervention by the FDA was its ruling that an oral contraceptive marketed as 'Marvelon' in many countries could not carry this name in the U.S. since it suggested that the drug was 'marvelous'. Similarly, 'Humulin' suggests that the product is human insulin, which is a false claim. More recently, the FDA rejected the name Acomplia (rimonabant), Sanofi Aventis' potential anti-obesity drug because the name would imply that the drug helps patients accomplish weight-loss, and it was felt that was misleading.)

The marketing of Humulin suggests that the product is human insulin, which is a false claim. Nevertheless, manufacturers re-enforced this misapprehension with a sophisticated and aggressive marketing strategy based, in part, on the premise that 'human' insulin is identical to insulin produced by nondiabetics and therefore must be safer and more effective than insulin obtained from animals. Thousands of physicians, targeted by drug company sales representatives, have internalized that message and have repeated it to their patients. You should be ashamed of your abuse of the media, Mr. Taurel.



As the book notes, Humulin and other synthetic insulins marketed by other companies are by no means identical to natural human insulin as their names imply (for one thing, Humulin is not produced by pancreatic beta cells, and it is missing several elements which found in natural insulins, including the beneficial C-Peptide). And an estimated 10% of all patients, particularly those who began treatment with animal-sourced insulins, have severe hypoglycemia unawareness that is a direct result of synthetic insulin (remember that type 1 diabetes is caused, in part, by an allergy to human insulin, so this is not so surprising in light of this fact).

The bigger issue is that while we all agree that the media's reporting is often lacking, one cannot manipulate that media on one hand while complaining about it on the other. None of us should buy that Lilly's overriding concern is patients. It isn't, otherwise the company would not be withdrawing insulin formulations that patients relied upon to force them to use more profitable new products. Don't expect us, as Lilly customers to agree with your manipulation of the media, nor as Lilly shareholders to justify your complaints.


Commentary: The Media on Drugs
By Sidney Taurel, published in The Wall Street Journal
November 27, 2007; Page A19

When it comes to describing the benefits and risks of prescription drugs, the hyper-competitive, around-the-clock media is rarely at its best. Call the following a case study in the challenge of doing right by doctors and patients -- in spite of the need to feed the media beast with copy.

Our story starts Oct. 24, when several media outlets reported that Eli Lilly and Company had halted two clinical trials for the drug prasugrel -- a possible new therapy for heart-attack patients that Lilly is developing with Daiichi Sankyo. The speculation that followed these reports was that the drug must have failed its initial trials. Within a few days the market capitalization of Eli Lilly fell by about $6 billion.

This speculation was unfounded and, incidentally, false. In early November, the academic TIMI Study Group announced the results of a massive clinical trial showing that prasugrel produced significant improvements in patient outcomes compared with current treatments.

Specifically, the trial, known as TRITON, showed that prasugrel produced a 19% reduction in relative risk for cardiovascular death, nonfatal heart attack, or nonfatal stroke when compared with the drug clopidogrel -- today's standard of care -- and had a favorable benefit-risk profile in a large majority of patients.

Statistical data can be interpreted in different ways. Some experts will reach more nuanced or skeptical conclusions about TRITON. But a Duke University cardiologist told this newspaper, after seeing the trial's results, "If you can't get a drug on the market with that kind of data, we should stop developing drugs."

So what happened in those days after Oct. 24? Lilly's goal was to turn over our prasugrel findings to doctors in a manner that left no doubt as to their scientific rigor and completeness. This meant publishing the findings in a highly respected journal and discussing them directly with top cardiologists, ahead of mass-media reporting. We decided to present these findings to the New England Journal of Medicine (NEJM) and the Annual Scientific Sessions of the American Heart Association (AHA) on Nov. 4.

NEJM and AHA asked for promises from Lilly and its partners, and we agreed, not to disclose any of the results of TRITON prior to Nov. 4. Such guarantees of exclusivity are not only common, but also appropriate, in focusing expert attention on important research. A definitive source and a "zero hour" of first-hand disclosure for complex scientific data help to limit misinformation.

Doctors and scientists at Lilly and Daiichi Sankyo, of course, had begun to analyze the results of TRITON in the weeks leading up to the AHA meeting. In addition to showing strong efficacy, the data also showed that in three small subgroups of patients, the drug at its current dosage raised the risk of major bleeding relative to its effect on preventing heart attacks.

Lilly had two small clinical trials of prasugrel underway for different research purposes, and we had received no reports of safety concerns from them. But when we saw the TRITON results, we put patients first. Based on the small chance that patients in the three identified subgroups might be given prasugrel and experience serious bleeding, we advised our researchers to suspend the two trials pending a review.

Enter the beast. Ten days before our "zero hour," word leaked out, causing us to confirm that the two prasugrel trials had been suspended, although our promises to NEJM and AHA prevented us from explaining why. The media entered a feeding frenzy, catered by commentators on Wall Street and elsewhere who speculated that prasugrel posed broad risks and had probably failed its major trial. Our stock began its trip south and, more seriously, some doctors and patients were left with false impressions.

Unveiling the data at AHA brought some relief. Still swimming against the tide of rumor, a few stories distorted the TRITON results, but most were balanced. In the end, the Food and Drug Administration will not rely on media reports to reach approval decisions. Lilly is confident that prasugrel will be given a chance to help patients on a large scale.

There are a few lessons here that need to be learned. For the pharmaceutical industry: Preserving the integrity of scientific data and protecting the safety of patients are always the right choices. Stock prices recover but trust is much harder to regain. Trust hinges on our openness in sharing everything we know about who should use our products -- along with when, how and at what dose -- and who should not.

For the media, if I may be so bold: Don't trade in leaks and rumors where scientific data are concerned. Damage to public understanding is hard to repair after it's been done. Wait for real numbers, and take the time to explain statistics and benefit-risk analysis, which cannot be conveyed in sound bites alone. And for would-be pundits: If you have not had firsthand exposure to the scientific results or specialized knowledge under discussion, then qualify your comments if you must make them at all.

We all have a stake in taming this beast -- not for the sake of any company or individual discovery, but for the sake of those who ultimately rely on accurate information for the care of patients.

Mr. Taurel is chairman and CEO of Eli Lilly and Company.

Indiana State Police Searching for 2 Truckloads of Stolen Insulin

This weekend, the media in Indiana reported that Indiana State Police were investigating a theft involving two truckloads of stolen insulin, undoubtedly from manufacturer Eli Lilly and Company, which manufactures most of the insulin sold in the U.S. in the company's Indiana facilities (although the company also has a substantial manufacturing operation in Puerto Rico, mostly for the insulin analog Humalog).

Reports indicated that the stolen trucks contained health and beauty aids and 21 skids of insulin stored in the refrigerated trailers, which were stolen from a Plainfield, IN trucking company between 11:45 p.m. Wednesday and 10:45 a.m. Thursday.

Indiana State Troopers continued Friday to try to determine how and why the trailers were stolen. An increase in truck traffic has occurred in the Plainfield area along with construction of several warehouses near I-70 and the Indianapolis International Airport.

One of the stolen trailers is a 2004 Utility, and the other is a 2006 Great Dane, according to the news release. The trailers' only distinguishing characteristics are their red axles and wheel hubs, troopers said.

The relevant trailers were stolen from Daum Trucking, along Indiana Route 267 just north of U.S. 40. The trailers were not painted with any company logo and had stainless-steel sides, State Police said. Other reports indicated that the license plate of the 2004 Utility trailer was Indiana 614231, and its VIN number is 1UYVS25384M157905. The plate of the Great Dane trailer is Indiana 609868, and its VIN number is 1GRAA062X6W705555. The two trailers could be worth more than $1 million.

Sgt. Rich Myers of the Indiana State Police said the thieves must have known what was in the trailers. Myers also says that by not maintaining the medicine properly, the thieves could be selling a toxic product.

"If this insulin is not maintained at a proper temperature, it can go bad, and if someone does take this insulin it can cause very bad sickness and even death."

At this time of year, the biggest concern is not excessive heat (which is also damaging), rather, freezing of the insulin. Either way, failure to maintain the temperature could put patients at risk.

Indiana State Police urged anyone who is offered insulin from other than normal medical and retail suppliers to contact the Indiana State Police or the nearest law enforcement authority to report the circumstances of how the insulin was offered. They can reach them at: (765) 653-4114. The toll-free number is: (800) 225-8576.


News Sources:
http://www.indystar.com/apps/pbcs.dll/article?AID=/20071123/LOCAL/71123021

http://www.indystar.com/apps/pbcs.dll/article?AID=/20071124/LOCAL/711240476/-1/LOCAL17

http://www.wishtv.com/Global/story.asp?S=7400876&nav=0Ra7

Seitsemän for Tuesday

I know that Chrissie tagged me for the seven meme, and maybe Gina(then again, it may have been Scott Johnson, but either way, I'm doomed!), and finally, Khürt tagged me, too. Whenever I think of seven ... I always think of the Morgan Freeman/Brad Pitt movie with all the creepy depictions of the seven deadly sins being carried out in the form of various ways to murder people. I suppose I could look on the brighter side, and assume it means I'm like Schoolhouse Rock's Lucky Seven Sampson, but lets not get into that right now.

Although I'm not crazy about these meme things, which in the snail-mail world would be called a chain letter, I'll comply simply because this week is likely to be a quiet one for me as far as postings. Tomorrow, I'm going to my parents' place in the leafy exurbs in Connecticut for the U.S. Thanksgiving holiday, so I'm unlikely to post anything else this week unless I have time (which means my 7 year old niece will be busy doing something else).

Anyway, here are Rules:
1. Link to the person's blog who tagged you.
2. Post these rules on your blog.
3. List seven random and/or weird facts about yourself.
4. Tag seven random people at the end of your post and include links to their blogs.
5. Let each person know that they have been tagged by posting a comment on their blog.

Seven random and/or wierd facts? Hmmmm, there are just so very many, where do I begin?

1. Its no secret I've lived with T1DM for 31 years now (God, how old does that make me?), but perhaps my readers were not aware that my older sister also has type 1. Compare that ratio to Bernard where one of his 5 other siblings has type 1. Regardless, because of that, diabetes was really never a biggie in my formative years because I grew up in a house where a majority (2 out of 3) of the children had this frustrating, never-ending chronic disease.

2. I'm cynical. OK, thats hardly a secret, but my cynicism is based on experience. I can honestly say that I think that insulin analogs (and all biosynthetic "humanoid" insulins, for that matter) do not work as well as the old insulins that kept me complication-free for two and a half decades, and the new stuff offer ... gasp, less predictability in my blood glucose levels. Are they faster? Sometimes, but predictability in my numbers was something I saw disappear after being forced to switch to biosynthetic "Humulin", an insulin which is is only genetically similar to insulin, but lacking some key elements since its made by injecting the human insulin gene into the e.coli virus. And after trying those patent-protected so-called "designer insulins" which BTW, have never been proven to improve hemoglobin A1C's, although they do cost about 50% more, I've concluded those are worse. Too bad the manufacturers want everyone to be on analogs because they are patent-protected for a few more years and can protect their revenue stream.

3. Along those lines, I will dispute anyone's claims that wearing an insulin pump is a liberating experience, virtually eliminates hypoglycemia, or offers the best in care available to treat type 1 diabetes available, and I have the experience necessary to make such an assessment. I tried pumping for almost 4 years, and did not find any of those claims to be accurate for me, so please don't tell people these things will happen -- they are not applicable to everyone, and the device is a nuisance to wear. However, I will say that the experience of pumping was one of the most informative experiences I ever had, and I learned things about managing the big D I would never have learned on MDI, so I don't think it was a wasted experience for me. But I will call you a "pump evangelist" if you try to convert me now, and thats not a term of endearment!

4. In addition to having grown up in Connecticut (and never having moved for the first 19 years), I went to college in the Boston area, and when I graduated, I returned home and commuted to NYC for a year. When an opportunity arose, I packed up and moved to the Monterey/Santa Cruz/San Jose, CA area, followed by a move to Foster City, and finally to San Francisco (I lived in Cow Hollow). In 1997, I moved to Newark, Delaware (for a short time) before settling into a place in Ardmore, PA just outside of Philly. Most recently, I called Port Washington (Long Island), NY home before moving to my current domain in Queens, NYC, which is three times as large and has a washer and dryer (how many residents of the city can say that?) On top of that, I also lived for 3 months in Helsinki, Finland. I can be polite in Finnish, and do not butcher the words, but beyond that, 3 months is not sufficient time to gain language proficiency. BTW, seitsemän is Finnish for seven.

5. I have a significant collection of TV Shows on DVD. I've lost track of how many (although they are organized by decade), but to give you a sample, I have different series' ranging from the 1950's to 2000's, including every episode of I Love Lucy/The Lucy Desi Comedy Hour (1950's), the entire series of Get Smart (1960-1970's), every episode of The Brady Bunch (1970's), the entire series of The Golden Girls (1980's), and yes, I even have more modern shows like Comedy Central's Drawn Together on DVD (season 3 is now on the air). My objective is to someday transfer all of the discs onto a massive hard drive on a Media Center PC so they are all accessible via remote control, but have no timeframes on when I get around to doing that.

6. I like all animals, and over my lifetime, I've had dogs, cats, hamsters, gerbils, fish, even cows and a pig. But my preferred pets are cats. No, this is not a dog person vs. cat person thing, but I just prefer the fact that cats are very low-maintenance animals who use a litterbox do not need to be walked twice daily, and also does not bark and slobber all over me. Plus, I can leave my cat Phyllis for 3 days and she is perfectly capable of caring for herself while I'm gone. Of course, Phyllis rides in the car all the time, and doesn't mind traveling with me. But, personality-wise, she is more similar to me -- more reserved and less likely to fall in "love" with a complete stranger, but is very social once she gets to know someone.

7. My great grandmother was Lithuanian, and over the years, I've grown fond of certain Lithuanian foods. On the surface, many dishes resemble the more widely known Jewish varieties of these foods (cabbage soup, rye bread, for example). But the difference might have some rabbis shaking their finger at you. Notably, pork (ham, etc.) is the most common meat used in a lot of Lithuanian cuisine, which is strictly taboo if one follows a Kosher diet. For example, to be made according to the family's traditional recipe, cabbage soup must be made from a ham bone, so the frozen Tabatchnick variety found in the frozen foods section of your local supermarket just won't cut it as far as flavor is concerned. I happened to visit Lithuania a few years ago, and would agree with travel guru Arthur Frommer when he says that for most U.S. travelers, the Baltic states are low on the radar, which is unfortunate. Many destinations in Latvia, Estonia and Lithuania offer a relatively inexpensive vacation compared to many of its neighboring countries in Europe and plenty of beautiful things to see -- culturally, architecturally, and geographically speaking. Vilnius is at times called "the New Prague" for its Baroque Old Town. He reports that the main exception seems to be that the unrelenting popularity of Prague has made that city pricier than Paris these days (not to mention more crowded).

So, I have taken the seven and diverged on different topics. For those of you who read all of them, maybe I have shared something you didn't know! I have skipped naming seven others to participate because, as Allison says, "I swear everyone has been tagged already… if you’re reading this and haven’t been tagged, consider yourself tagged!" Have a happy Thanksgiving holiday!

Your Rx Buying History is For Sale

Every once and a while, I conclude that I cannot improve upon someone else's work, and so it is the case with patientprivacyrights.org's new campaign to highlight that your prescription drug buying history -- including name, address, date of birth and drug regimen is FOR SALE. In fact, each day all 51,000 pharmacies (including mail-order pharmacies like Medco and Express Scripts) in the U.S. download, transmit and sell personally identifiable information for every drug they disburse. Even if you pay cash. One of the biggest data miners to profit from this data is IMS Health, a company who compiles prescription sales data for Wall Street analysts (or anyone else who wants to buy it) and sells it for outrageous sums of money, even though you never agreed to be included!

The main purchasers of this data are insurance companies and underwriters, pharmaceutical companies and other data miners. Arguably, the data can be bought and sold by anyone who wants to purchase it.

Don't remember agreeing to this? Well, you didn't. Take a few seconds to watch the following video:



The fact is that no one has ever given informed consent for their personal information to be used in this way. No one has ever been given the right to opt out of this practice.

You can help Patient Privacy Rights make your prescriptions private via the following actions:

1). Sign the Campaign for Prescription Privacy petition to demand that pharmacy chains stop selling our health secrets.

2). Spread the word. Please do like I have, by forwarding this video to all your friends and family and making it available in online communities so that we can protect our private data.

I hope you will give this serious consideration, because today, your prescription purchases are really anything but secret.

The Business of Diabetes: Signs Suggest Lilly's Type 1 Diabetes Strategy May Be Evolving

Since 1923, Eli Lilly and Company's strategy for type 1 diabetes has been fixated on insulin replacement, and more recently, pushing the idea of intensified insulin therapy. Although Lilly's Humalog was the first insulin analog on the market, over the past decade especially, Lilly took its eyes off the ball and lost its position of dominance in the U.S. type 1 diabetes treatment market to rival Novo Nordisk and more recently, some share to Sanofi Aventis.

For the past several years (my first post on this subject was in 2005), I chronicled Lilly's squandering of insulin market share in the U.S., from as much as 85% of the U.S. insulin market back in 1995 to just 43% in 2006 according to data from IMS Health. This year, the company beefed up its salesforce for diabetes products to match Novo Nordisk's significant sales staff. But the market share slide cannot be resolved simply by hiring more people to push the stuff, the company must offer products to meet the needs of doctors and their patients. But Lilly should have been investing in this a decade ago, but didn't bother as it rode the Prozac pony to blockbuster status, only to see its share of that drug eaten by generics manufacturers when its patent expired. The company also invested in treatments for schizophrenia and other mental health conditions, while its insulin business was ignored by executives in Indianapolis, assuming its market dominance would continue in spite of massive changes in the way drugs are bought with managed care providers demanding big price breaks and a need to minimize the number of providers.

Management's solution to problems in the insulin business: a smarter insulin pen. Investors should be skeptical. Today, Lilly is a one-trick pony in the insulin market, offering no long-acting insulin whatsoever since removing Ultralente from the market in 2005, while rivals Novo Nordisk and Sanofi Aventis both have long-acting insulin analogs on the market. Indeed, Sanofi's Lantus is the world's best-selling insulin today. The long-term trend for Humalog has been a steady decline in market share to Novolog and Apidra.

The one bright spot for Lilly is continued strength in its Humulin biosynthetic insulins, although in the U.S., these products have lost market share, largely to Novo Nordisk's Novolin biosynthetic insulins.

This summer, Lilly hired Dr. Robert J. Heine to manage Lilly's diabetes business. But as I noted in September, the selection of Dr. Heine was not a terribly logical choice to manage this business. Dr. Heine's primary research interests and expertise is in the epidemiology and pathophysiology of type 2 diabetes, not type 1 diabetes. But Lilly's type 2 business actually remains fairly healthy (the Byetta franchise which is exclusively for the type 2 audience remains very healthy, although profits are shared with partner Amylin Pharmaceuticals, Inc.) while Lilly's insulin business aimed largely at the type 1 audience is the business that's in terrible shape, and slick pens are probably not sufficient to turn that business around.

This week, there was another announcement (see here) from JDRF and Eli Lilly and Company (on top of one announced in February) and in late October, and Lilly announced they had partnered with MacroGenics, Inc. in which the two companies have entered into a global strategic alliance to develop and commercialize teplizumab, a humanized anti-CD3 monoclonal antibody, as well as other potential next generation anti-CD3 molecules for use in the treatment of autoimmune diseases, including type 1 diabetes. As part of that deal, Lilly will acquire the exclusive rights to the molecule.

"We remain committed to maintaining our leadership role in diabetes care, including an expanded presence in the area of type 1 diabetes" David Moller, M.D., Vice President of Endocrine and Cardiovascular Research and Clinical Investigation at Eli Lilly and Co. said in a company press release.

These moves suggest that Lilly may be re-thinking its strategy for the type 1 diabetes market. As I commented on Allison's blog, recent announcements regarding Eli Lilly and Company and JDRF suggest that just maybe, Lilly has come to the realization that if they cannot win in the insulin market with Humalog only, perhaps funding efforts that might arrest the autoimmune attack that causes type 1 diabetes in the first place will give the company continued relevance in the type 1 market. It is a risky strategy, but the rewards, if successful, could be significant.

Dr. Jeffrey Bluestone at U.C. San Francisco has pioneered early work in this field, and clinical trials in Europe suggested that it works effectively on newly diagnosed patients, reducing their total daily dosage requirements for insulin and providing ongoing protection from hypoglycemia. But the big unknown is, and few studies have investigated, whether this treatment might also be applicable to long-standing type 1 patients. Perhaps Lilly will investigate this, and I would bet they also try combining treatment with Byetta, which has been proven to restore beta cell mass in patients with type 2 diabetes. Trials are planned to investigate this might help retain beta cell function on islet transplant patients, and there is considerable interest in looking at whether Byetta might also help restore beta cell mass in patients with type 1 diabetes. It may be wishful thinking for Lilly, but only trials will provide an answer to this question.

To be sure, others are pursuing similar strategies, notably, Dr. Denise Faustman will kick off her own trials at arresting the autoimmune attack in both newly diagnosed and long-standing patients with type 1 diabetes, reportedly starting in 2008. MacroGenics solution is just one of several in the groundbreaking field of immunology, a relatively understudied field of science that seems integral to solving the type 1 diabetes issue.

The bottom line seems very clear: Lilly has a tough road ahead of it as far as restoring its past dominance in the U.S. insulin market. Generics WILL emerge in the not-too-distant future, and its unclear whether the Humulin business will survive without major market share losses. Keep in mind that half of Lilly's insulin franchise consists of Humulin sales. It does seem, however, that Novo Nordisk plans to eliminate all forms of synthetic "human" insulin (Novolin) according to statements from that company's Chief Financial Officer. That could enable Lilly to retain some of this business, assuming Novo follows through on its plan. But Lilly could be the thorn in Novo Nordisk's side that prevents it from happening.

Lilly must consider partnerships, notably with Flamel Technologies S.A. of France. In 2003, Bristol-Myers Squibb announced that they had entered into a licensing and commercialization agreement to develop and market Basulin®, the first controlled release, unmodified synthetic "human" insulin to be developed as a once-daily injection for patients with type 1 or type 2 diabetes. But in late 2004, Bristol Myers terminated that agreement, thus opening the door for Lilly to step in. Flamel, whose U.S. headquarters are in Washington, D.C., has continued with human clinical trials using what they call Medusa®, a nanotechnology solution which can carry polyamino acids (think insulin), which the company claims is a very versatile protein carrier for the development of novel and second-generation long-acting protein medicines, such as insulin and human growth hormone among others.

In September, Flamel entered into a development and license agreement with Wyeth Pharmaceuticals. The agreement was for the development and licensing of a marketed protein to be delivered using Flamel's Medusa technology. Flamel will receive an upfront payment and potential development fees, milestones and royalty payments, the terms of which are not disclosed. However, appears that the Wyeth agreement was not an exclusive agreement, whereas the original agreement with Bristol Myers Squibb was, thus creating an opportunity for Lilly.

Stephen H. Willard, Flamel's Chief Executive Officer said at the time of the announcement "As with the four previous Medusa relationships that we have entered into this year, this agreement concerns our new uniform polymer which is applicable to a wide variety of proteins and peptides. This new relationship contributes to our goal of building a diverse set of relationships for our Medusa platform, which we expect will continue to grow. We are pleased that Wyeth has chosen to license our Medusa technology and are looking forward to working in the development of this exciting opportunity."

In October 2007, Flamel Technologies announced positive preliminary Phase I data from a trial comparing the safety, tolerability, and long-acting activity of its Basulin product compared to Sanofi's Lantus insulin analog. The press release said very specifically that "Flamel is seeking a licensing partner for that product."

Okay, Sidney Taurel (Eli Lilly and Company's Chairman and CEO), as well as Dr. Robert J. Heine, M.D. AND J. Scott MacGregor (a Communications Associate for the insulin business at Lilly), listen up: Your insulin business is in bad shape, and the prospects of generics could enable companies like Sandoz (Novartis), Teva, Barr and other generic manufacturers to eat into your lucrative Humulin franchise, too. Humalog may be a decent product (at least from a business perspective), but its clearly not enough to restore your former market share in insulin, and I would add that Pfizer's decision to pull the plug on Exubera suggests that your AIR inhalable insulin product may be only a niche market opportunity (one which rivals Novo Nordisk also plans on competing in). Take my advice, and look into partnerships with Flamel, or your days in the insulin market in the not-too-distant future could be numbered.

A Slightly Different Spin on World Diabetes Day

When I began blogging back in 2005 (I was on back then, too, Kerri!), there were only a few of what I like to refer to as D-Bloggers. Since then, the community has grown substantially, creating an online community of hundreds (maybe even a thousand or more?) of us. World Diabetes Day is "celebrated" on Banting's birthday. I say "celebrate" because in spite of progress, this is really not a day anyone should celebrate (I certainly don't), as its a chronic disease that requires ongoing and expensive maintenence tools. Diabetes sucks, there's no better way of stating the obvious, and treatment has improved slightly, but its arguably the most challenging chronic condition to try and manage, and the new tools frankly haven't made life dramatically easier because we are tasked with trying to replicate a physiological response with non-physiological treatments -- a huge flaw.

The theme of this year's World Diabetes Day campaign is Diabetes in Children and Adolescents. In many parts of the world, insulin, a life-saving hormone required for survival, is simply unavailable (or is available but remains inaccessible for reasons of economy, geography or constraints on supply). As a consequence, many children die of diabetes, particularly in low and middle-income countries. The World Diabetes Day 2007 and 2008 campaigns set out to challenge this and firmly establish the message that 'no child should die of diabetes'.

That is what my diatribe today is about. I'd like to call your attention to Insulin For Life (IFL), which is an Australia-based not-for-profit, non-government organization which was established in 1999 that aims to donate unused insulin, glucose test strips and other diabetes supplies that are urgently needed in many parts of the world, to help develop and implement sustainable improvements insulin supply in countries in need, and to mentor similar programs around the world.

For that reason, its worth calling attention Saudi Arabia's recently announced plans to develop its own (with help from scientists in Brazil) domestic supply of insulin which is actually quite admirable. Although Saudi Arabia can easily afford it, and many other countries cannot, I still support their efforts. The more suppliers of insulin in this world, the better as far as I'm concerned. The oligopoly has resulted in poor quality, and increased cost with little innovation. Saudi Arabia's insulin manufacturing plans were driven, in no small part, based on last year's uproar in the Islamic world about a newspaper in Denmark (home to Novo Nordisk, Saudi Arabia's largest insulin supplier) which pubished some comics which were deemed offensive to the Islamic faith. That brought the country to realize that they really had few viable alternatives other than Eli Lilly and Company from the U.S., or the French-German company Sanofi Aventis. (Although a handful of manufacturers still exist in Poland, Russia, Argentina and India, the fact remains that the number on a worldwide basis is pretty small). Regardless of your personal feelings on Saudi Arabia's insulin plans, the fact is that there are simply too few suppliers of insulin in this world, and we should support MORE manufacturers of insulin, not the trend of less we have witnessed in recent years which enabled Novo Nordisk to acquire Brazil's largest insulin supplier (Biobrás) a few years ago. Insulin should not have to be shipped to Africa or Asia from Denmark, Germany or Indiana, it should be accessible locally just as other medical treatments are.

That point aside, I had the great pleasure of meeting two of the people from Insulin for Life, a truly incredible organization two years ago at the American Diabetes Association Scientific Sessions Vendor Exhibition in Washington, DC. I must admit that I was very disappointed that the ADA relegated such noble organizations as this to the periphery of the floor (although at least they were on the same floor, unlike at the 2000 conference in San Antonio). Meanwhile, muli-billion dollar diabusinesses such as Novo Nordisk, Eli Lilly and Metronic Minimed just to name a few who had elaborate displays that commanded the attention of healthcare professionals with information about more accurate and/or simpler blood glucose monitors and insulin delivery systems, while nonprofits like Insulin for Life (as well as advocates for curing diabetes) were woefully underrepresented and the few that were there were relegated to the periphery of the display floor.

Without the attention-grabbing gimmicks of the companies selling diabetes management products, unfortunately, their messages sometimes get lost and healthcare workers return home, telling their diabetic patients only about all the new technology that can help them manage their condition, not about how they could donate their unused insulin (or all their own free samples that salespeople leave at their offices) to needy children in more remote parts of the world.

On this World Diabetes Day, and in the name of Diabetes in Children and Adolescents, I support efforts to produce MORE suppliers of insulin (and other supplies) in this world, not less as we have seen in recent years. I support India's aspirations to become another global supplier in insulin. Also, while the big organizations like JDRF get a lot of attention, the fact is that smaller organizations like Insulin for Life have a much more immediate impact on the lives of children around the world, and we should support their efforts to get insulin to children and adolescents who need it around the world!

Regards!

Big Pharma Lobbyists Delay Generic Insulin (yet again)

As the D-Blogger community already discovered from Vivian's post, our do-nothing Congress has delayed passing legislation (until 2008) which would remove the final impediments for generic insulin, not to mention other (in the words of the FDA) "follow-on" protein products (that bill is known as S. 623/
H.R. 1038, the "Access to Life-Saving Medicine Act of 2007").

As I have chronicled throughout the year (see here for the original article, including links to follow-up coverage), the reasons for lack of generic insulin are multi-faceted, but the biggest single reason is that manufacturers of generic products, which include such well-regarded manufacturers such as Novartis' Sandoz unit, Israel-based Teva Pharmaceuticals, and U.S.-based Barr Pharmaceuticals among others are lacking guidance from the U.S. Food and Drug Administration on how to apply for and obtain approvals. That is somewhat ironic, considering the FDA practically falls all over itself to tell brand-name manufacturers what they need to do to get FDA approval.

As I reported a few weeks ago, the legislation faced a possible veto-threat from President George W. Bush, who seems to enjoy vetoes that hurt average Americans, in spite of having vetoed far fewer bills than other President's in recent history. But as Newsday is reporting this morning, the real reason for the delay is because of lobbyists for big drug companies, not because of a weak veto threat from the President (especially since the bill seems to have widespread, bi-partisan support and Congress likely had sufficient votes to override a Presidential veto on this bill).

If you are as disgusted by this as I am, you should write to your legislators and complain about the fact that they have done close to nothing during 2007! Its not only the lack of progress on Iraq that has driven Congress' record-low approval ratings, its also lack of progress on the domestic front, too.


Lobbying Stalls Generic Drug Legislation
By Frederic J. Frommer, Associated Press Writer
7:47 AM EST, November 13, 2007

WASHINGTON - Legislation aimed at speeding the availability of cheaper generic drugs has stalled in Congress in the face of major lobbying by the drug industry.

The Senate bill would ban most settlements known as "reverse payments," in which a brand-name company pays a generic manufacturer to delay the introduction of the generic drug. The Federal Trade Commission, which has called on Congress to take action, says such settlements could cost American consumers billions of dollars.

An Associated Press review of lobbying reports, from July 1, 2006, through June 30, 2007, found that $38.8 million was spent by at least a dozen generic and brand-name companies and their trade associations on issues including the Senate legislation. The lobbying reports do not specify how much of that money was directed at the reverse payment bill, and they are not required by law to do so.

More than half of those expenses were piled up by the Pharmaceutical Research & Manufacturers of America, or PhRMA, which represents brand-name drug companies. PhRMA spent $19.5 million in the 12-month period ending June 30 on in-house lobbying expenses, an increase of about $3 million over the previous 12-month period.

And the Generic Pharmaceutical Association reported lobbying expenses of around $420,000 for the first six months of this year. It did not report lobbying on the bill in its year-ending 2006 report. The remaining $19 million was spent by a variety of drug companies, including Bayer Corp., Schering-Plough, Pfizer and Teva Pharmaceuticals USA.

"Lobbyists have a lot of influence in Washington," said the bill's sponsor, Sen. Herb Kohl, who chairs the Senate Judiciary subcommittee on antitrust, competition policy and consumer rights. "If we can just get this to a vote, it will be pretty hard for people to vote against it. A vote against this is a vote against consumers."

Kohl, D-Wis., also chairs the Senate Special Committee on Aging, where he has pushed for generic drugs as a way for seniors to save money on their medications. Generic drugs are 30 to 80 percent cheaper than brand-name drugs, according to the Generic Pharmaceutical Association.

Kohl has offered the reverse payment legislation for the past two sessions of Congress. This year, House supporters introduced a similar bill, which remains in committee. Neither bill has come up for a vote, although the Senate bill did make it through the Judiciary Committee a few months ago.

In May, Kohl tried to get a vote on the Senate floor under a procedure known as unanimous consent, but Republicans objected. Sen. Mike Enzi, R-Wyo., said Sen. Jon Kyl, R-Ariz., and others involved with the legislation wanted more time to work on it.

Kyl asked the Justice Department's antitrust division for its views on the bill and is waiting for a response, said Kyl spokesman Andrew Wilder. The antitrust division declined to comment.

Sen. Orrin Hatch, R-Utah, has expressed concerns about Kohl's bill. Hatch issued a statement saying he voted to move the bill through committee this year "with the reservation that we find a balanced solution, one that bars anticompetitive settlements without jeopardizing the very kind of settlements that are critical to consumers and taxpayers."

"We haven't reached that balance yet, so it's understandable this bill has not moved forward," Hatch said.

In 1984, Congress passed the Hatch-Waxman Act, which established procedures to encourage generic companies to challenge patents before their expiration. In recent years, generic companies have increasingly resolved such challenges through settlements in which the generics receive cash or lucrative licensing and marketing agreements.

The drug companies are required to file their settlements with the FTC. Two federal appeals court rulings in 2005 upholding the legality of reverse payments have made it more difficult for the agency to block them.

In one of those cases, Barr Laboratories Inc. abandoned its successful challenge to AstraZeneca PLC's patent for the breast cancer drug tamoxifen. In exchange, Barr received a $21 million payment and entered an agreement with AstraZeneca under which Barr sold tamoxifen provided by AstraZeneca.

Consumers filed a lawsuit. The 2nd U.S. Circuit Court of Appeals upheld a federal judge who had concluded that the agreement did not violate federal antitrust laws. In June, the Supreme Court refused to take up an appeal.

A plaintiff in that case, Helen Donega of North Adams, Mass., said she was saving only about 5 percent off the brand-name price when she purchased the Barr generic tamoxifen in 1998 and 1999. Donega, who had insurance through Medicare but no drug coverage, said she had to pay between $85 and $90 a month for the drug.

She eventually bought tamoxifen in Canada for about one-10th of the price she was paying in the U.S.

Donega, 75, who had a mastectomy and has been cancer-free for several years, said she was amazed when she learned of the deal between Barr and AstraZeneca, which sold tamoxifen under the brand name Nolvadex. AstraZeneca's patent on the drug has since expired.

"I must have been naive. I thought the government was on our side," she said. "No, the government isn't on our side. Big PhRMA is powerful and has a lot of money. That's whose side they're on."

AstraZeneca spent just under $2.4 million in lobbying expenses over the 12-month period ending July 1 on issues including the reverse payment bill.

In an e-mail statement, AstraZeneca spokesman Tony Jewell said the settlement with Barr Laboratories was meant to resolve a patent dispute, not to delay the generic tamoxifen.

Barr spent $660,000 in the same 12-month period. At a Senate Judiciary Committee hearing this year, Barr Chairman and CEO Bruce L. Downey said the company settled the case with AstraZeneca because it thought it would lose its patent challenge on appeal.

"We took payment, we took a license, and we entered the market early with tamoxifen," he said. "And over the course of our license, we saved consumers about $300 million on that product."

Not all patent litigation settlements between generic and brand name companies involve payments, and Kohl's bill bans only those where the generic company receives something of value. The legislation would allow, for example, a deal in which the two sides merely compromise on the date that a generic can enter the market. And Kohl recently agreed to add a provision that would exempt some reverse payment settlements if the FTC determines they would benefit consumers.

The FTC has called on Congress to pass legislation to crack down on the reverse payment settlements, although it hasn't endorsed any specific bill.

"Such settlements restrict competition at the expense of consumers, whose access to lower-priced generic drugs is delayed, sometimes for many years," FTC Chairwoman Deborah Platt Majoras said in testimony before a House task force in September.

Generic and brand name drug companies argue that a ban would be counterproductive. PhRMA senior vice president Ken Johnson said in a statement that pharmaceutical research companies invest billions of dollars developing new medicines, and that patent rights help the companies recoup those investments and fund new research.

Jake Hanson, a lobbyist for Barr Laboratories, said that the settlements are sometimes necessary when a generic company considers all the ramifications behind a patent challenge.

"Sometimes as you're moving through discovery and different levels of a court case, you realize that it may not be a slam dunk," Hanson said.

Americans May Be Over-Vaccinated; Is T1DM An Adverse Effect?

Last week, an article published in The New England Journal of Medicine written by Oregon Health & Science University researchers suggested that Americans may be over-vaccinating ourselves. Specifically, the authors found that antibodies from some vaccines actually stay around in the bloodstream for much longer than previously thought, which means that the current schedules for some vaccinations may be overkill. The study found that protection from conditions such as measles, mumps and rubella following exposure to the diseases were, in most cases, maintained for life. For more background, see The Wall Street Journal health blog posting here.

"If we can continue to improve our vaccines, someday we might be able to give one shot and give lifelong immunity," said Mr. Slifka, associate professor at the Oregon university's Vaccine and Gene Therapy Institute.

Some vaccines certainly require less frequent re-vaccinations. Indeed, some countries such as Sweden have changed their vaccination policies and doctors in that country are now advised to offer tetanus re-vaccination only once every 30 years.

While many public health advocates claim that booster shots of vaccines is not harmful, others aren't as easily convinced. Some groups (I am think of autism advocates, for example) argue that vaccinations are the reason behind the growth in the brain disorder that affects 3 areas of mental development: communication, social interaction, and creative/imaginative play. However, while there is conclusive evidence that the artificial preservative known as thimerosal used in some vaccines is linked to autism, the fact is that the use of thimerosal has declined significantly since the 1980's, and is now very uncommon in vaccines sold today. Parents can, of course, verify the absence of thimerosal before having their child given a particular vaccine.

Ironically, in spite of the relatively weak link between vaccines and autism, advocates against vaccinations working on behalf of that condition have proven far more vocal than other, often more dangerous conditions such as type 1 diabetes. For whatever reason, the findings of Dr. J. Bart Classen, a Maryland immunologist proving that certain vaccines are the largest cause of type 1 diabetes in children have received less public attention. Specifically, Dr. Classen's data shows that vaccines cause approximately 80% of cases of type 1 diabetes in children who have received multiple vaccines starting after 2 month of life. Specifically, his data included vaccines for pertussis, mumps, rubella (mumps and rubella vaccines are among those found to be given too frequently in the U.S.), as well as hepatitis B, hemophilus influenza and others. However, the data indicates people with vaccine-induced type 1 diabetes may not develop the disease until 4 or more years after receiving a vaccine. He argues that its not the vaccine itself, but rather the recommended schedule, and that more can be done to limit the negative impact. For more complete background information on the vaccination link between some vaccines and type 1 diabetes (including data on class-action lawsuits on behalf of people with type 1 diabetes pending who received certain vaccinations) please see here for details.

D-Blog Day

As you probably know, my friend Gina at The Diabetes Talkfest Blog started blogging about life with Diabetes and realized there were many of us out there. Although I don't have the latest count, I believe we number somewhere between 300 and 1,000. She called it D-blog Day, and I wanted to acknowledge the occasion with this posting. Happy D-blog Day!

Washington News You Should Know About

I have been absent as of late, largely because I have been a bit under the weather with bronchitis which has rendered me pretty sick. However, I have remained on top of issues that should be of interest to people in the diabetes community.

Most notable were two news stories from this morning's Washington Post. The first story was regarding a debate over whether the results of government-funded NIH research should be made freely available to the public, which had potential to make a big step toward resolution as members of a House and Senate conference committee met to finalize the 2008 Department of Health and Human Services appropriations bill.

While it sounds like common sense, believe it or not, today, not all research paid for by U.S. citizens is accessible to them. A two-year-old National Institutes of Health policy encourages, but does not require, NIH-funded scientists to publish in open-access journals. The current NIH Public Access Policy, which was first implemented in 2005, is a strictly voluntary measure and has resulted in a deposit rate of less than 5% by individual investigators, so the policy has largely failed. While there are many small not-for-profit societies who publish journals, the overwhelming majority of biomedical journals are now published by international giants - Elsevier, Wiley/Blackwell, Wolters Kluwer, which are for-profit publishing companies, not groups of scientists and/or doctors.

As the Post noted, the basic idea is that consumers should not have to buy expensive scientific journal subscriptions, or be subject to costly per-page charges for non-subscribers in order to see the results of research we have already paid for with our taxes. Rather, we should be able to access this information on the Internet for free because we have paid for this research. The new rule would enable scientists to publish anywhere they want, although the scientist(s) receiving NIH funding would be required to place a copy of the final version of the paper into PubMed Central, a government database that is free to anyone, and those articles would be available 12 months after the publication of the article in the medical or scientific journal. A number of years ago, scientific papers were published in common scientific journals of the day, but were not copyrighted and could be freely copied. That has changed in the past 30 years especially, and today, the publishers essentially own the article (largely because most journals require authors to sign the rights over to the journal) content, a sweet deal -- if you're a journal publisher. But taxpayers aren't getting their money's worth when the research remains locked away in publisher's databases who claim they own the rights to the content we paid for. Advocates assert that open access will speed innovation by making it easier for the results to be shared and enable others to build on those findings.

Director Elias A. Zerhouni said "Congress recognizes that, in the Internet age, unimpeded access to publicly funded research results is essential for the advancement of science and public health."

Not surprisingly, this legislation has gained widespread bi-partisan support in both the U.S. House of Representatives and the U.S. Senate. But the danger is that President George W. Bush may veto the bill. With both Senate and House appropriation committee chairmen in favor of the legislation, under normal circumstances, the language requiring the change would normally be virtually assured. But the Post reports that Capital Hill watchers say that given President Bush's threat to veto the bill for budgetary reasons and the likelihood of a continuing resolution (which would not have the new language) it might be too soon for the open-access movement to publish a victory paper.

The other article related to the U.S. Food and Drug Administration (FDA). Although the volume of prescription drugs and drug ingredients coming into the country from foreign manufacturers in developing nations (notably India and China) has exploded in recent years, the FDA's budget for foreign inspections has not kept pace and will actually be lower in 2008 than it was in 2002, according to Congressional investigators. The article says that means foreign drug and drug ingredient makers are inspected on average once every 8-12 years, while American-based manufacturers must be inspected at least once every 2 years.

I won't elaborate much further on that other than to say that the FDA's user fees for non-U.S. based manufacturers should be increased significantly to pay for inspections. Although I hate the user-fee system, but if we're going to have one in place, then we should make sure those costs are equitably distributed so we can have sufficient inspections. Enough said.