News of Interest

This morning's Los Angeles Times has two articles that may be of interest to the diabetes community. I have summarized the key elements here, but included references to the original articles for full details.

Big Pharma Spent Big Dollars Lobbying in 2006

The first article reported that the drug industry spent a whopping $155 million lobbying the federal government from 2005 to mid-2006, setting an all-time record that the industry might just top this year as Congress considers high-stakes legislation for the industry and consumers, a public interest group said in a report Monday. The industry's budget enabled drug makers to field about 1,100 agents to lobby congressional committees and administration offices in each of the last two years, the study said. As for the prediction about this year, as my readers may be aware, there is pending legislation which would enable "generic" (the FDA prefers the term "follow-on protein products") biopharmaceutical medicines such as insulin which the industry is fighting hard to make sure does not pass. The industry is also working to make sure the prohibition against Medicare negotiating drug prices for seniors in its prescription drug program remains intact, something Congress is looking into as the initial Bush Administration estimates proved to be significantly smaller than the actual cost of the Medicare drug benefit. The new Congress has also promised to re-visit the issue of permitting drugs to be imported from other countries like Canada, something else the industry has fought hard to prevent.

"Essentially what they [the pharmaceutical industry] did is blocked any legislation," said M. Asif Ismail, director of the center's project to monitor the drug industry. "There have been several attempts to revisit this issue, and importation is still illegal."

In addition to lobbying, the phamaceutical industry also spent more than $19 million on political contributions to candidates in last year's Congressional election, supporting mainly Republican candidates. However, the electorate grew unhappy with the way the war in Iraq was being managed by Republican leadership, enabling Democrats to seize control of both the Senate and the House of Representatives in the November election.

Finally, the industry also pays for the FDA in the form of user-fees. Legislation authorizing the FDA's user-fee system will expire this year unless Congress acts. Such must-pass legislation often attracts amendments. The pharmaceutical industry has agreed to hefty user-fee increases that would pay for new safety reviewers at FDA and help set up a computerized surveillance system to aid in detecting harmful side effects in new drugs. The hope is that by agreeing to these fees, they can persuade legislators that other legislation that the industry opposes would be an unncessary burden on the drug industry. That, at least, is the theory.

U.S. Patent Office Invalidates 3 Human Stem Cell Patents

A second article is reporting that U.S. Patent and Trademark Office has invalidated three broad patents for human embryonic stem cells that have been blamed for slowing research in the highly visible field of regenerative medicine. The rulings, from the U.S. Patent and Trademark Office, were preliminary — the patents are still enforceable in the interim, pending a final review in court.

The field of regenerative medicine is seen as a potential key to reversing type 1 diabetes once the issue of autoimmunity has been addressed. So far, the consensus seems to be that more will need to be done in order to return patients to insulin-independence because there is insufficient beta cell mass to free patients from the daily burden and risks associated with insulin replacement. Science hopes to be able to culture beta cells in vitro which could theoretically be transplanted back into patients whose bodies have destroyed these vital cells, and even better, the cultured beta cells could be customized to each patient.

The patent office ruled that the discovery of embryonic stem cells from primates — including humans — was not worthy of patent protection because scientists had already used similar methods to isolate embryonic stem cells from mice and other mammals, and described the cells' potential for producing medical therapies. The patent office issued its decisions Friday and released them to the public Monday.

The first of the three controversial patents was issued in 2001, three years after University of Wisconsin researcher James Thomson became the first to isolate stem cells from human embryos donated by fertility clinics. But as the field of stem cell research heated up, the Wisconsin Alumni Research Foundation, or WARF, gained a reputation for driving a hard bargain with universities and companies that wanted to use human embryonic stem cells.

The federal patent examiners cited patents and research papers going back to 1983 showing that stem cells harvested from mammalian embryos could be kept alive indefinitely while maintaining the ability to become heart muscle, nerve fiber or any other kind of cell. They noted that a 1992 patent involving mice stem cells described the potential for using the same techniques to create human embryonic stem cells.

"They [the U.S. Patent Office] rejected every one of the claims," said John Simpson, stem cell project director at the Foundation for Taxpayer and Consumer Rights in Santa Monica, one of the public interest groups that brought the challenge last year.

The patents have been a nagging problem for stem cell scientists, who have been worried about the costs and restrictions imposed by the patent holder, WARF. Some U.S. companies moved their research operations overseas, where the patents are not in force, after failing to strike a licensing deal with the Madison-based foundation, which manages the university's intellectual property.

After numerous complaints, WARF softened its requirements last year and reduced fees and legal requirements for academic researchers. But researchers still bristled at the idea that the cells, a natural product of human development, could be patented. On Monday, the U.S. Patent and Trade Office agreed.

Advice to Pediatric Endocrinologists: Grow Up - Part 2

As some of my readers may recall, last year, I had a posting called "Advice to Pediatric Endocrinologists: Grow Up" in which I noted that many endocrinologists who specialize in treating type 1 diabetes limit their practices to pediatric patients, as if the children they treat never grow up. I happened to stumble upon an article that was published in February 2007 that validated many of my initial reactions and wanted to share it.

What I found most interesting was the fact that some pediatric endocrinologists from Johns Hopkins in Baltimore are developing a transitional care program meant to address these very issues. Although the program has yet to become widespread in the U.S., it does serve as an important reminder that the needs of adults with type 1 diabetes are unique yet under-served, but perhaps if the program is successful, it will appear elsewhere in the future. One can certainly hope!



Leaving the nest with Type 1 diabetes
by Kristin Vorce, The Examiner
Feb 1, 2007

BALTIMORE - Each year more than 13,000 children in the United States are diagnosed with Type 1 diabetes, according to the Juvenile Diabetes Research Foundation. That is 35 children per day whose parents will likely monitor every aspect of their care and treatment until they leave home.

When these children become adults, they are suddenly on their own, said Dr. Greg Clark, an endocrinologist at Johns Hopkins. Complicating things, most adult diabetes cases are Type II, which is sometimes called adult onset diabetes.

"There aren't many adult endocrinologists who specialize in Type 1 diabetes," he said. "After they've left their pediatrician most [Type 1 diabetics] end up with a doctor who doesn't understand the disease at all."

This is why Clark is launching a new transitional care program teaching young adults to treat Type 1 independently.

A person with Type 1 has an immune system that destroys cells making insulin, a hormone critical to processing sugar in the blood, Clark said.

Clark, diagnosed with Type 1 at age 11, knows what it is like to take insulin injections and test his blood sugar by pricking his finger for blood four to six times daily. "It's a very difficult disease to treat because it requires so much on the part of the patient," he said.

Clark establishes relationships with patients with Type 1 in the pediatric clinic at Johns Hopkins before they transfer to his adult practice, he said.

The University of Maryland Medical Center has a similar transitional program. Young adults learn to keep in touch with their endocrinologist without nurturing parents calling the shots, said Debra Counts, director of pediatric endocrinology.

"In the pediatric model it's 'our disease,' " Counts said. "In the adult model it's 'my disease.'"

When patients with Type 1 move into college dormitories, they need to bring much more than a refrigerator and television. They should pack two blood glucose meters with extra batteries. They should also give to their resident assistant a glucagon kit in case they have severe low blood sugar, according to The Juvenile Diabetes Research Foundation.

Morgan Gilsan, a 20-year-old who attends Villa Julie College, said she sometimes thinks people do not know there are two types of diabetes.

"It just seems like they're forgetting how difficult it is for people with Type 1 diabetes and how we need help," Gilsan said.

She has learned to handle the daily routines on her own, and her three roommates know what to do if her blood sugar gets too low. Gilsan said she feels comfortable with Clark because he has Type 1.

"I went to a couple of other doctors and they were either too strict or too lenient," she said. "They didn't really understand the disease very well."

Although there are medications available to combat Type 1, they have serious side effects. Clark is currently working on stem cell research to find a safe cure.

kvorce@baltimoreexaminer.com

URL for this article:
http://www.examiner.com/a-540846~Leaving_the_nest_with_Type_1_diabetes.html

Ignorance is NOT Bliss

Yesterday's Minneapolis Star Tribune featured an article in the business section about Medtronic Inc., which happens to be based in Minnesota. Of course, Medtronic is best known within the diabetes community as the parent of Minimed, the first and largest manufacturer of insulin pumps, as Medtronic acquired the Northridge, California-based insulin pump manufacturer in 2001 for $3.7 billion. However, Medtronic's diabetes division is one of the company's smallest -- accounting for about 8% (or $722 million) of the company's total annual revenue.

One of the more noteworthy pieces of the story was the fact that Medtronic recently commissioned a survey conducted by Harris Interactive which found that 80% of the American public cannot distinguish between type 1 and type 2 diabetes. Even more troubling was the finding that nearly 70% (67% to be exact) of those who responded to the poll incorrectly believed there is already a cure for type 1 diabetes! Key findings were as follows:

67% mistakenly believed there is a cure for type 1 diabetes

51% knew there were two types of diabetes

36% thought there was either a "type 3 or 4" diabetes

25% believed that proper diet could "cure" the disease

32% believed exercise could be a "cure"

Sources: Medtronic Inc., Harris Interactive survey of 2,436 American adults, Minneapolis Star Tribune.

I suspect that few people with type 1 diabetes would doubt the accuracy of these findings. Unlike other medical conditions, diabetes is largely invisible to the naked eye (one reason why I support the Diabetes Made Visible effort). You could pass 100 people with diabetes during the course of the day and never be able to identify them. Also, because type 1 diabetes patients are usually normal weight, they do not display any overt symptoms.

Medtronic said it would spend an undisclosed amount on educational initiatives to inform the public about the disease. This includes an informational website (www.realdiabetescontrol.com) and local events throughout the country to spread the word about therapy options. The first event is scheduled for May in Miami.

I believe the American Diabetes Association has done very little to educate the general population as to the distinctions between type 1 and type 2 diabetes, and has actually worked to blur the distinctions (see my previous post on this subject here). However, the fact that the ADA president-elect Dr. John Buse has already received a degree of notoriety by his willingness to tell things like they are suggests that a changing of the guard at the ADA could bring about positive changes for the historically slow-moving organization!

Original reference URL:
http://www.startribune.com/535/story/1083648.html

FDA: Simple generic biologics may require less data

Continuing the ongoing coverage I have given to the issue of legislation to support the introduction of generic insulin (including my original post, a follow-up based on NYT coverage, the news that legislators had finally introduced a bill that would force the FDA to permit generic biopharmaceuticals where patents had already expired, as well as a few relevant follow-ups, including a story that a coalition of businesses' (including the largest U.S. employer, General Motors) Congressional testimony that generic biotech drugs would be safe while cutting costs, and another story that outlined the estimated savings that generic insulin could have on the nation's healthcare budget.

On Monday, there was a follow-up story published by Reuters that indiated that some generic biologics would require more data than others. This tends to apply more to newer, more complex treatments such as those for cancer, anemia and other conditions. By comparison, insulin and human growth hormone, both of which have lengthy histories in clinical usage are also structurally fairly simple proteins to begin with, therefore, these likely require less data. The bottom line, however, is that the pending legislation would enable the FDA to make those calls on a case-by-case basis, thus ensuring that the agency can make informed approval or decline decisions. But without legislation to enable this, we will continue to be denied healthy competition in the insulin market, as well as many newer biologic medicines.

However, another article published by the Associated Press (I caught it in the Philadelphia Inquirer) warned that it could be a decade or more before science is available to safely approve generic versions of biotech drugs in the way the agency now approves knockoffs of traditional medicines. FDA deputy commissioner Janet Woodcock testified before Congress saying that while the FDA now could establish the safety of new versions of simple protein-based drugs (such as insulin or human growth hormone), it would likely "be a stepwise progression over a decade or so" before the agency could scientifically verify that a knockoff version of a complex biotech drug was similar to the original. This suggests that insulin and human growth hormone are likely to be among the first to see guidelines, ones that incidentally, the FDA did not release as they were supposed to back in 2001.

In a less-than-surprising response, Inger Mollerup, a Vice President from Novo Nordisk said that if Congress created a system to approve cheaper protein-based drugs, it should be similar to one already used by the European Union. Under the EU process, generic biotech companies still must conduct extensive studies to show the safety of their versions. Even after these studies are completed and the product is approved, knockoff biotech drugs are not considered "interchangeable" with the original product, meaning a patient must get doctor approval before switching from the original drug to a generic. The FDA calls these "follow-on protein products".

Critics, including myself, think that the EU process is unncessarily complex and costly for simple follow-on protein products, and that the process being outlined by Congress enables (OK, maybe it forces them) to outline its own requirements for what types of clinical trials will be required, and how extensive these will be. The FDA has been dragging its heels on this for far too long. Effectively, well-characterized products like insulin and human growth hormone may not require the same extent of clinical trials to be undertaken by generics manufacturers as complex protein-based medicines. If it needs a model of how to proceed, I would argue that the EU is not who the U.S. should be following. The FDA need look no further than the recent application for Novartis-Sandoz's Omnitrope (a follow-on form of Pfizer's Genotropin human growth hormone), which was submitted with preclinical, clinical, and comparability data, as well as literature references to the FDA's original decision on the original manufacturer's product.

Although I don't want to be over-optimistic, increasingly, its finally starting to look like this legislation may finally move forward in the U.S.!



Complex generic biologics need more data: FDA
Mon Mar 26, 2007 2:48PM EDT
By Susan Heavey

WASHINGTON (Reuters) - Cheaper, generic versions of more complex protein-based drugs will need more data than simpler compounds to prove their safety and effectiveness, a U.S. Food and Drug Administration official said on Monday.

"The amount of assurance and the amount of data that would be needed is really based on how complex something is and how well it can be characterized," FDA Deputy Commissioner for Operations and Chief Medical Officer Dr. Janet Woodcock told lawmakers.

Other factors, including whether a drug would be used long-term for chronic diseases, will also impact what kind of testing will be needed, she added during a hearing of the U.S. House of Representatives Committee on Oversight and Government Reform.

Her comments come as Congress weighs legislation to give the FDA authority to approve generic versions of biological medicines such as Genentech Inc.'s cancer drugs Herceptin and Avastin, as well as anemia drugs such as Amgen Inc.'s Epogen and Aranesp and Johnson & Johnson's Procrit.

Unlike conventional, chemical-based drugs, biologics are derived from living cells and are usually injected or infused.

At issue is whether generics could be considered either interchangeable or similar to their more expensive counterparts, and how Congress should set standards.

The FDA already has the power to clear generic versions of traditional medicines. More than 9,000 such products are already on the U.S. market and make up 60 percent of all prescriptions, according to the agency.

Committee Chairman Henry Waxman, the California Democrat who convened the panel, has introduced legislation that would allow the FDA to review generic biologics. A similar bill has been introduced in the Senate.

Brand name drugmakers and other opponents say biologics are too difficult to duplicate and even small differences can affect safety and efficacy. But supporters, including insurers and patient groups, argue competition would make them more affordable than branded versions that can cost tens of thousands of dollars a year.

At the hearing, Woodcock said the FDA has the expertise to evaluate such generics, also known as follow-on biologics, but the ability to compare them to original products will depend on the molecule's complexity.

Some biologics, such as insulin or human growth hormone, are considered simpler than other proteins used to treat cancer, anemia and other conditions.

"Although this may be currently possible for some relatively simple protein products, technology is not yet sufficiently advanced to allow this type of comparison for complex protein products," she said in her testimony.

When asked how long it would take technology to catch up, Woodcock said it would be an ongoing process.

"It's going to be a step-wise progression over a decade or so," she said.

URL for this article:
http://www.reuters.com/article/healthNews/idUSN2634323120070326

Federal Budget Priorities

This morning's Boston Globe has an editorial about how, on an inflation-adjusted basis, the National Institutes of Health (NIH) budget actually declined by 13% last year. (Of course, this followed dramatic increases between 1998 and 2003 which led to a doubling of the NIH's budget.) The NIH's budget has been flatlined at about $28 billion for the past 3 years, outpaced by 9% inflation.

In fact, Men's Health is reporting that the 2007 budget for the Department of Health and Human Services, under which both the CDC and NIH operate, shows that grant monies for "Preventive Health and Health Services," "Public Health Improvement," and "Children's Hospitals" have been slashed by almost $375 million while "Bioterrorism" funding has increased to $1.7 billion, up nearly tenfold in the past 5 years.

As the Boston Globe editorial notes, the actual impact of the budget issues facing the NIH is that scientists are forced to spend more time writing grant applications and less time in the laboratory, and it also creates a bias towards research in tried-and-true areas and away from the unconventional. But as the editorial notes, the clampdown on spending means that the great majority of new research grant applications now go unfunded. Across the board, it seems that just 20% of applications win grants, while even successful grants are regularly cut 24% to 29% from the requested amount.

The sad reality is that promising discoveries recently made in the field of type 2 diabetes noted in the Men's Health article now face shutdown while the newly-created Department of Homeland Security has turned into yet another government wasteland, with such seemingly insane budget items recently reported by Newsday, as $18,000 to equip the Santa Clara, California, bomb squad with Segways; $30,000 to ensure a defibrillator is on hand for every Lake County, Tennessee, high-school basketball game; $500,000 worth of security gear to the town of North Pole, Alaska, population 1,778; Kevlar vests for the police dogs of Columbus, Ohio; and the list goes on.

The President's priorities were no secret, and the fact that he enjoyed a rubber-stamp Congress for most of his tenure helped to create this unhealthy (in more ways than one) environment. But November's election changed all of that, and the last 2 years of the Bush White House are finally bringing some public attention to some of this. The real issue is that in order to preserve the nation's laboratories and ensure resumed progress in medical research, Congress needs to increase NIH funding by at least the 6.7%/year for 3 years in order to recoup what has been lost to inflation. President Bush has promised to veto (only the second veto since he's been in office, first of which was to say no to expanding stem cell research) any budget that does not increase funding for the Iraq war. The real question is whether Congress will gather sufficient bi-partisan support to override his veto threat?

The Business of Diabetes: Beckman Coulter News

The following article was released Sunday in The Wall Street Journal online. On the surface, it would not appear directly relevant to diabetes as few people with diabetes have ever heard of the company involved. However, few people realize that in 2004, the Massachusetts General Hospital trustees established a relationship with Beckman Coulter in order to significantly discount $1,000,000 of equipment needed to establish the blood assay for Denise Faustman's and David Nathan's human clinical trials. Beckman Coulter is a leading manufacturer of biomedical testing instrument systems, tests and supplies that simplify and automate laboratory processes. Finalizing the blood assay is required before the human clinical trials can begin (otherwise, it would be impossible to measure whether the trial is arresting the autoimmune process which causes type 1 diabetes), and those human clinical trials are expected to begin in 2008.

Regardless of what people may think of the price tag for this equipment, the need for assays is undeniable, especially in a well-designed clinical trial. The fact that Beckman Coulter is able to orchestrate an acquisition for $1.55 billion speaks volume about the health of the company involved. Read on for details.


Beckman Will Buy Biosite for $1.55 Billion
By Rhonda Rundle, The Wall Street Journal
March 25, 2007

LOS ANGELES, Calif. -- Beckman Coulter Inc. said it has signed a definitive agreement to acquire Biosite Inc. for $1.55 billion, in a combination that will expand Beckman's presence in the immmunoassay segment of the medical test market.

Beckman Coulter said it will acquire all of Biosite's outstanding stock in a cash tender offer of $85 a share. Beckman, based in Fullerton, Calif., said the transaction is expected to immediately accelerate Beckman's revenue growth and improve operating margins. Beckman said it expects the acquisition to boost earnings in 2008 and beyond.

The merger "will position Beckman Coulter as a leading provider of immunoassay tests, especially within cardiac diagnostics," said Scott Garrett, president and chief executive officer. He said the company remains "on track to achieve our full year 2007 outlook, as stated in our February 8 earnings release, excluding any impact from the Biosite acquisition."

Beckman said its offer for all of Biosite's outstanding common stock is conditioned upon at least a majority of the outstanding Biosite shares being tendered, as well as satisfaction of regulatory and other customary conditions. Approval by Beckman Coulter's shareholders isn't required. The combination is expected to close in the second quarter. Biosite is headquartered in San Diego.

Write to Rhonda Rundle at rhonda.rundle@wsj.com

URL for this article:
http://online.wsj.com/article/SB117485766625848294.html

Book Review: "Bittersweet: Diabetes, Insulin, and the Transformation of Illness"

Author: Chris Feudtner, Review by: Scott Strumello

Hardcover: 312 pages; Dimensions (in inches): 1.00 x 9.56 x 6.40
Publisher: University of North Carolina Press; (May 26, 2003)
ISBN: 0807827916

Well, I've had this book review included among my draft postings for a while, and its probably time to post it. I have read this book, and have a slightly different perspective than the target audience, namely medical professionals, but I also share some of their observations. Read on for my complete review!


Although Bittersweet: Diabetes, Insulin, and the Transformation of Illness was first published in May 2003, it has not really hit the radar screens of many patients with diabetes as say, Michael Bliss' The Discovery of Insulin did. That is unfortunate, because Bittersweet provides a useful perspective that is not seen in so many of what I consider to be a "sickeningly sweet" context for many diabetes publications today (self-help books frequently written by people who tell us that we can successfully control diabetes, all it takes is a positive attitude -– despite the fact that few of these books are written by people who have any clue what its actually like to live with diabetes 24/7/365 themselves). Bittersweet is more of a history lesson, but an important one which addresses not only diabetes, but the impact of medical care on health over time. The author, Chris Feudtner, uses the term "Bittersweet" to describe medicine not as a history of consistent and steady progress as it is often viewed, but frequently a compromise between the lesser of two lousy choices. In many cases, treatment falls short of the ultimate goal of actually making people better. This is true for not only diabetes, but for many other conditions, ranging from asthma to AIDS.

To be sure, Bittersweet is not the kind of reading I would recommend doing before going to sleep. It is rather dry reading and takes a while to get into reading it, but the perspective provided makes it worthwhile. Feudtner examines the history of insulin therapy, and describes what he calls the transformation of illness. The idea is simple enough, although as The New England Journal of Medicine reviewer originally said, "It has not been stated so clearly and compellingly before now". New therapeutic techniques often do not conquer or eradicate diseases but, instead, transform them, and sometimes in ways that physicians cannot imagine.

Feudtner builds on a detailed examination of the clinical records and correspondence from the clinic of the famous Boston physician Elliott Joslin to chart the effects of insulin therapy on the patients and physicians who actually pioneered it. The records that Feudtner studied contained the extensive correspondence of Joslin's original patients, who reported their successes and challenges in using insulin. The treatment of diabetes allowed patients to be involved in the day-to-day management of a disease in a way that was unprecedented. Feudtner carefully sorted through the documents of a first generation of patients who entered this regimen of regular injections, monitoring, and dose adjustments. He also notes that what we find in these letters are not private reflections on illness by its sufferers, but by people who were writing to their doctor. One especially poignant example was from a patient named Guy Rainsford, who kept up a decades-long correspondence with Joslin and illustrated his medical concerns in part through a series of penciled cartoons. Rainsford's sketches featured himself as the quirky and irascible protagonist of an ongoing struggle against his ailing body, armed with, or beset by, a sometimes-bewildering array of syringes, retorts, chemicals, and charts in an effort to try and manage his blood glucose levels.

Indeed, insulin transformed the illnesses and the lives of the patients who came under its influence. Early proponents of insulin treatment, like Joslin, realized they were at the cusp of a new era. The sections of the book about the treatment of childhood diabetes before 1922 were very informative, and make patients realize that although current treatment is far short of a cure, it's still better than what became of patients before insulin's discovery, but the overall lesson is that the medical profession has not been a history of ongoing success as they would like us to believe. Interestingly, even the earliest insulin users expressed similar complaints about the ability to comply with the relentless rigors of medical advice that arose in the form of dietary restrictions, guidance and treatment and frustration with their inability to truly control their condition. The introduction of insulin in 1922 transformed the acute, rapidly fatal course of a type 1 diabetic coma into a chronic illness that was instead monitored and managed over the years. But the limitations of insulin treatment were painfully evident even in Joslin's day. Insulin treatment often stopped cold the ravages of ketoacidosis but created in its wake a host of late complications in the vessels of the retina, brain, heart, and kidneys of patients with diabetes.

Even today, in spite of improvements in the management of diabetes, sometimes even the most motivated and compliant patients still suffer complications, showing us that the idea of "control" is really a misnomer. "Manage" is probably a more appropriate term because physicians and patients do not have absolute control over all metabolic variables, and therefore our ability to actually control the condition remains limited. More recently, the DCCT showed that although intensified glucose management dramatically reduced the likelihood of complications, it still failed to completely eliminate diabetes complications (indeed, something like 60% of the intensive treatment group actually suffered from some form of complication, although some proponents argue this is because they did not intensively manage the condition from diagnosis). In addition, the intensified treatment therapy brought with it a statistically significant increase in the incidence of severe hypoglycemia, and although more accurate dosing and delivery via insulin pumps and better insulin analogs have improved insulin therapy slightly, the reality is that a patient with type 1 diabetes today still faces many of the same challenges as patients in the early 1920's did. Although refined control may further reduce the likelihood of complications, or at least reduce the severity of them, even that is unlikely to ever completely eliminate diabetes complications. As The New England Journal of Medicine reviewer noted, what changed most was the expectation of success.

Interestingly, in March 1999, another famous Canadian diabetes researcher, Dr. James Shapiro and his team again raised the expectation that an actual cure for diabetes was no longer a completely unrealistic expectation. But the lesson we must draw from Bittersweet is that although our expectations for success have grown, the medical profession's track record of success is decidedly more limited. As a result, our expectations for a cure will probably need to be moderated as well. Frequently, I hear people with diabetes who claim they expect a cure without immunosuppressants. But as Bittersweet serves to remind us, medical history is filled with stories of transformed illnesses, and type 1 diabetes is perhaps the most well-documented example. The result may be a "cure" that includes immunosuppressants, but perhaps fewer and less toxic ones are a more realistic expectation. As both a historian and a pediatrician, Feudtner is sensitive to the ironies implicit in insulin therapy. As The New England Journal of Medicine reviewer originally noted in his review of this book, "The transformation of disease, as exemplified by the case of diabetes, is a valuable and elegant concept that serves to remind us that the tally sheet for medical science must carry a column for debit as well as credit." Bittersweet serves as a valuable history lesson and in spite of advancements in treatment, patients with type 1 diabetes today will probably find a lot more in common with the earliest users of insulin than they might expect.

Coming Soon: New Insulin Pen for Apidra & Lantus Users

Until very recently, Apidra users who for whatever reason did not use an insulin pump had limited choices when it came to portable insulin delivery: either a predrawn syringe, or Sanofi-Aventis' clunky insulin pen, the OptiClik insulin pen device. Users of the OptiClick complain about that pen for a variety of reasons. Most notably, the pen is not as small as insulin pen devices from rivals Novo Nordisk or Eli Lilly and Company. Plus, a box (or a 3 month supply) of the insulin cartridges are significantly larger than rivals and take up a lot of real estate in the refrigerator. Another complaint (from someone who had their bag stolen last fall) is that the OptiClik pens can only be obtained from a physician, so if you should lose or somehow have a pen malfunction, its not like you can go to the nearest Walgreens and pick up a new one over the weekend, it requires a trip to your doctor's office and time off from work. If you don't have a vial of Apidra in the fridge and suffer a similar issue, you'll be hard-pressed to draw insulin from the OptiClik pen cartridges because they contain the mechanics of the piston built into the insulin cartridge itself, rather than the pen device. As a result, withdrawing insulin from the cartridge itself would leave a huge air bubble in the cartridge, so a word of advice is to ask your doctor for two! And then there's the inability to dose in 1/2 unit increments, which many parents of children with diabetes and type 1 adults alike complain is unacceptable dosing precision. I won't go into that here, but my posts on Lilly's Humapen Memoir have covered that issue in detail.

In Sanofi's recent investor presentation, the company announced plans to introduce a new, disposable insulin pen to be branded SoloSTAR®. While the rationale for this pen was never addressed, the fact that Sanofi is the only one of the "big 3" insulin manufacturers who does not offer a disposable pen, and perhaps some of the complaints I described previously may have contributed to this decision.


While American consumers may have a slightly longer wait, today, Sanofi-Aventis announced it would introduce the SoloSTAR pen in Europe starting in April. The first launch of SoloSTAR insulin pen is planned in Germany in April 2007. Lantus® SoloSTAR and Apidra® SoloSTAR previously received European Commission approval, although FDA status is still undetermined at this time. Sanofi-Aventis is reporting that the company is currently building significant manufacturing capability to support worldwide launches, so the U.S. is likely to be announced sometime later this year. The pens themselves are made by a Swiss company. The product is aimed squarely at the vast type 2 market, as the company's blockbuster Lantus will be the first insulin to see the new pen, and they are touting the fact that the pen has the highest dose range of any disposable pen on the market, going up to 80 units in a single dose. Most type 1 patients would probably die from such a large dosage, as the total daily dose for most type 1 patients is usually less than half that maximum. Regardless, the news is likely to be welcomed as a big convenience for Apidra and Lantus users everywhere (or those considering these insulins).

According to the press-release, "SoloSTAR is a new, easy-to-use disposable pen for administration of Lantus and Apidra. SoloSTAR reduces the injection force by 30% or more in comparison to other leading disposable pens. This is beneficial for all people with diabetes and in particular for those with lower grip strength and the estimated up to 58% of individuals with limited joint mobility of the hand. SoloSTAR has the highest dose range of any disposable insulin pen with doses up to 80 units adjustable in 1 unit steps. To help with correct insulin identification and differentiation SoloSTAR is also the only disposable insulin pen with a completely different pen colour for each different insulin."

The color-coding feature is quite useful, as similar-looking pen devices can be easily confused otherwise. While the SoloSTAR pen may not be the answer patients have always waited for, it does put Sanofi-Aventis' insulin portfolio on a more competitive footing with rivals Novo Nordisk and Eli Lilly and Company. Now, if anyone speaks French, perhaps they can work with me on contacting company headquarters in Paris about 1/2 unit dosing?!

http://www.medicalnewstoday.com/medicalnews.php?newsid=65482&nfid=crss

FDA Indicates Biotech Knockoffs Might Have Different Status Than "Generics"

Pharmacy benefits managers would not be able to simply subsitute generic biopharmaceuticals for the brand-name products without consent.

Continuing my ongoing coverage on this topic (including my original post, a follow-up based on NYT coverage, recent news that legislators have finally introduced a bill that would enable the FDA to approve generic biopharmaceuticals, and my post on the Express Scripts study that suggested that generic insulin could save $797+ million in the first year, and in excess of $16 billion over 10 years), today's Associated Press featured an article that I think should address anyone's remaining concerns about opening the door to generic biopharmaceuticals (or as the FDA prefers to call them, "follow-on" protein products) such as insulin. Its important to note that the pending legislation would enable the FDA to require additional clinical trial results if the agency feels they are necessary to approve a generic biopharmaceutical.

But by classifying follow-on protein products as something other than generics, the FDA is indicating that generic biopharmaceuticals would not exactly be considered generics, which are identical, or bioequivalent to the brand name drug in dosage form, safety, strength, route of administration, quality, performance characteristics and intended use and are therefore interchangable with the brand name. Instead, follow-on protein medicines would be considered similar enough to be used in place of a brand-name, but not quite interchangable. The bottom line is that pharmacists would not be able to subsitute a cheaper generic version without telling you. This is basically the situation with insulin today. Sure, Humalog, Novolog and Apidra are rapid-acting analogs, but a patient cannot necessarily switch from one brand to another without making adjustments. I think the Associated Press calling them a "lower" status than a generic is a misnomer, rather it would be a different status than a generic, meaning it can be used to treat the same condition, just not interchangably with the brand-name version -- adjustments might need to be made. This would provide patients with access to lower-cost insulin, but would not force them to switch simply because their healthcare provider wants you to take the cheaper version.

For more complete details on this subject, please see the article that follows, as well as the links above.

FDA: Biotech Knockoffs Earn Lower Status
By Andrew Bridges, Associated Press
March 15, 2007

WASHINGTON -- Copycat versions of pricey biotech drugs may be relegated to a status below that of generic versions of traditional chemical drugs, the head of the Food and Drug Administration suggested Thursday.

Dr. Andrew von Eschenbach told pharmaceutical executives that such knockoffs would be considered only "similar" to brand-name drugs. The FDA commissioner later told The Associated Press that would mean knockoffs would not be interchangeable, or able to be substituted.

That definition mirrors one used by the European Medicines Agency, the FDA's European counterpart. It would draw a distinction between biotech knockoffs, which the FDA says it still lacks the legal and scientific frameworks to approve, and the generic versions of traditional drugs already available.

Today, traditional drug knockoffs or generics are identical to their brand-name versions and can be swapped or substituted for one another. That would not be the case with a knockoff biotech drug deemed only "similar," even though its effect on patients would be the same.

"We recognize that the end point would be what could be best described as similarity. Similarity in the sense that when a doctor gives you the product -- delivered it to a patient -- it will achieve an effect that is similar to the effect that we expected from the innovative ... compound," von Eschenbach told the annual meeting of the Pharmaceutical Research and Manufacturers of America, the drug industry group.

Unlike traditional chemical-based drugs, biotech drugs -- also called biologics or biopharmaceuticals -- are made from proteins taken from living cells. Generally, biotech drugs are far more costly and complex than traditional drugs to both make and copy.

Because of that complexity, the FDA and the brand-name drug industry both maintain it would be difficult to ensure the safety and effectiveness of the knockoffs, sometimes called follow-on protein products.

A bipartisan group of lawmakers recently renewed the push to give the agency that legal authority. The FDA says it continues to develop the scientific guidelines required to consider applications from would-be manufactures of the copycat biotech drugs.

The Generic Pharmaceutical Association says the FDA already has the scientific knowledge to approve knockoffs, just as it now can sign off on the changes made by brand-name biotech companies in how they produce their drugs.

"The commissioner is acknowledging that when brands make changes to their products, they are no longer identical to the approved product, but FDA follows sound science to review and approve these changes. This same sound science will be used to review biogenerics for safety and efficacy," said Kathleen Jaeger, the generic drug industry group's president and chief executive officer.

This article originally appeared at:
http://www.washingtonpost.com/wp-dyn/content/article/2007/03/15/AR2007031501650.html

Lilly Responds

As a follow-up to yesterday's post, I am pleased that J. Scott MacGregor who handles public relations for the Humalog brand at Eli Lilly and Company, actually contacted me to share the company's official perspective on the question I posed, and I felt it was worthy of sharing that response with my readers, so here it is:


The development of Memoir spanned 7 years and cost millions of dollars to bring to market here in the U.S. The task of developing the sophisticated electronics -- and then determining how to fit the chip into a pen device that would be both accurate and reliable, dose after dose, and then manufacturing it on a broad scale -- was a daunting hurdle overcome by top-flight device engineers and scientists, both at Lilly and our partner in development, Battelle Medical Device Solutions in Columbus, OH. This was no standard task, and Memoir is no standard pen. Its electronics and memory feature are unlike any pen on the market for the delivery of insulin.

Developing a pen with a memory feature was the direct result of feedback from patient research. Patients told us they wanted an insulin delivery device that would deliver simple and accurate dosing and could help them simplify the daily management of diabetes by easing the burden with a memory feature. Our engineers then set out to deliver on those patient needs, and we're pleased that patients who use Humalog here in the U.S. can now benefit from this innovation.

Could these same engineers design a device with memory that could dose in half-unit increments? Possibly, yes, in the future. But that will require additional years of development, and we didn't want to delay the introduction Memoir to patients here in the U.S.

Clearly, there are some people using insulin who may benefit from half-unit dosing -- in particular, we believe a half-unit pen may be attractive to people who don't need large amounts of insulin or parents of some children with diabetes. HumaPen Luxura HD was developed to fill this need. We're very pleased to be launching Luxura HD in April, and recognize that some people may benefit from a half-unit pen and others from a device with memory such as Memoir.

In the end, the answer is simple: we listen to patients and try to develop new devices that will meet their needs. But the story of the development of these two pens is not nearly as simple as it may seem.

One additional clarification -- Memoir is manufactured in Clinton, MA. The Luxura HD is manufactured in Wisconsin by a different manufacturer.



First, I would like to extend my sincere appreciation to Scott MacGregor for sharing that with us. It certainly clarifies the company's thought process and what led to the two pen delivery device products that Lilly is now introducing. However, I would like to call attention to a few elements.

If Lilly began development of the HumaPen Memoir 7 years ago, yet researched the wants and needs of patients in January 2007, there is something of a disconnect unless other research was done during the product development phase. It would appear that the research was done to prove there was a need for the product and its features, rather than investigating what patients actually wanted or needed. In other words, the horse was put before the cart.

To be sure, the Memoir was a great idea, and there is no doubt that Lilly spent considerable time and resources developing it in order to better meet the needs of patients, but it seems painfully evident that the needs of patients with type 1 diabetes, most of whom remain sensitive to small changes in dosage, have fallen behind the massive type 2 market in the eyes of company management. The real question is whether this is the wisest choice for the management of the Humalog franchise?

In terms of overall patients, type 1 patients remain a key constituency for the insulin franchise, and one I would argue that the company can no longer afford to ignore or consider as secondary to the massive type 2 market. Why? There is no doubt that insulin-using type 2 patients buy much more insulin -- some type 2 patients are so insulin resistant that they require U-500 insulin vs. the standard U-100 -- but their purchase volume does not align quite so well with the overall number of buyers. There are an estimated 4 million insulin users in the U.S., and we know that all 1.1 million type 1 patients are included among them. That means that while the type 1 market consumes less insulin volume overall, they still account for 27.5% of all the people who actually buy insulin. It is already well documented that most type 2 insulin users have far less risk of hypoglycemia than patients with type 1, therefore a half-unit difference in dosage is unlikely to have a material impact. But for many type 1 patients (including many adults), a half unit can literally mean the difference between hyperglycemia and hypoglycemia.

Clearly, many type 1 patients choose an insulin pump because it delivers insulin with a level of precision that they cannot obtain in any other way. Pen devices are clearly aimed at patients who do not pump insulin, whether by choice or due to economics, or because they are recently diagnosed. But the number of new users with type 1 is increasing almost as quickly as the type 2 market. Why? For the type 2 market, many endocrinologists see the hyperinsulinemia which is a symptom of many type 2 patients as part of the problem, rather than the solution. After all, excessive insulin contributes to inflammation as well as elevated lipids and blood fats and other co-morbidities associated with the metabolic syndrome. Among type 2 patients, insulin sensitizer drugs such as metaformin will always be a first-line treatment because they are effective yet inexpensive. As more modern treatments including incretin based treatments like exenatide (Byetta) which Lilly co-markets with partner Amylin Pharmaceuticals emerge, insulin will decrease in relative importance for treatment among the type 2 market. Lilly has been a key beneficiary of this trend (as the marketer of Byetta), but it also suggests that the ever-expanding treatment options for the type 2 market will further erode the need for insulin among this group except among patients with long-standing type 2 diabetes.

While the HumaPen Luxura HD does put Lilly on a more competitive footing with rival Novo Nordisk (and they've lost a LOT of market share to Novo Nordisk in the last 5 years), it really does little to differentiate Humalog or to make prospective users say "I really want to use Humalog because Lilly's pen device helps me in a way that Novolog cannot". And then there is Sanofi Aventis' Apidra, the newest rapid-acting insulin analog. Apidra will clearly continue growing from its tiny sliver of the insulin market, but the real question is where the growth will come from. Although Sanofi's OptiClick pen is not much of a threat today, that could be modified fairly easily. Its painfully evident that more precise dosages were obviously an afterthought for the product developers, not something that was incorporated right from the very beginning. Yet in spite of the Lilly's research, which included both type 1 and type 2 patients, which revealed that 84% said a memory feature would be valuable, and fully 94% said its important to know if they missed an insulin dose, the HumaPen Luxura HD fails to address these needs -- a lost opportunity at establishing customer loyalty.

The most important take away is that while the type 1 market may be smaller in terms of purchase volume for insulin, insulin manufacturers simply cannot afford to overlook the fact that they remain very large in terms of number of overall users. That's something that a company selling insulin cannot afford to overlook.

HumaPen LUXURA™ HD: What The Hell Is Lilly Thinking?

The following press release was in today's news. While the portion about Lilly's HumaPen MEMOIR™ is old news at this point, starting in the third paragraph of this release is news pertaining to the HumaPen LUXURA™ HD, which will apparently be available by prescription starting in April 2007. As I've noted previously, the device (the HumaPen LUXURA™ HD) will enable delivery of anywhere from 1-to-30 units of Humalog in 1/2 unit increments (beginning after the first unit). However, as the following photos will demonstrate, I wanted to pass along the following piece of additional information that I received from Lilly's PR firm:

"I wanted to clear up any lingering confusion about the HumaPen LUXURA™ HD's features - currently, it does not have the memory function that the HumaPen MEMOIR™ has."

Its very unclear why on earth Lilly would choose NOT to enable the memory function in a pen that doses in 1/2 unit increments, and I would dare suggest that the price would need to be significantly lower before patients are willing to rush out to buy a pen like this. It seems that this was obviously an afterthought, not an integrated piece of the company's marketing strategy, which it really needs to be.

As you can see in the photograph below, the HumaPen LUXURA™ HD is the teal-colored device and notice that it does NOT have an LCD screen which does appear as a part of the HumaPen® MEMOIR™ (pictured immediately below).


A photograph of the Lilly HumaPen LUXURA™ HD is pictured above. Note the absence of an LCD screen, which indicates that this pen device lacks the memory function.

By comparison, the Lilly HumaPen MEMOIR™ is pictured here, and as you can see, the LCD screen is where patients can access information on their recent dosages.

I'm not a pharmaceutical analyst for Wall Street, but I would say that Lilly has some additional work to do if they believe these new pen devices are going to help turn its floundering insulin business around any time in the immediate future. The new pens are attractive and appear to be solid and well-made (they are manufacturered, according to the press, in Clinton, Massachusetts, rather than in China as virtually all glucose meters and most test strips are). Still, if there is no memory function, then the HumaPen LUXURA™ HD has few advantages over Lilly's disposable insulin pens other than having the ability to deliver more precise dosages and being more attractive, but is it worth the price? I would suggest a far less costly option might be to consider a Wright Pre-filled Syringe Case instead.

All I can say is what the hell was Lilly thinking? What's so difficult about having a pen that can dose in 1/2 unit increments AND capture the date, time and amount of the last 16 dosages? Its not rocket science here, it involves having a finer thread on the piston in the pen device, and developing a chip that can count in 1/2 unit increments rather than full unit increments. While Lilly notes that 4 million Americans use insulin, I would just note that approximately 1.1 million of them (or about 27%) are insulin-sensitive type 1 patients who are likely to need greater dosing precision.

Also in today's news, Representative Henry A. Waxman, Democrat of California and chairman of the House Oversight and Government Reform Committee sought information about allegations of inappropriate marketing by Eli Lilly and Company.

The letter to Eli Lilly requested information about a schizophrenia drug, Zyprexa, citing allegations that the company "misled physicians and inappropriately promoted off-label uses" of the drug. The company's efforts to encourage Zyprexa for off-label uses like treating dementia was the subject of an article last year in The New York Times.

He asked Lilly for lists of studies conducted on Zyprexa as well as documents related to marketing plans, among other information.

Meanwhile, the afforementioned press release follows.

Lilly Introduces World's First Digital Insulin Pen With Memory
March 13, 2007

Eli Lilly and Company today announced the launch of the first insulin pen with memory, HumaPen® MEMOIR™, to help simplify the daily management of diabetes.

MEMOIR is designed to meet the needs of people with diabetes who take several shots of mealtime insulin each day. It presents sophisticated technology and features in a consumer-friendly "push-to-know" digital display that allows patients to record and review their last 16 insulin doses, including the priming doses.

Many insulin users need multiple shots per day, so the ability to record doses and the time of the dose may help simplify the daily management of diabetes. This is especially important for both patients and physicians when developing a diabetes treatment plan that utilizes accurate recording of mealtime doses. MEMOIR is now available by prescription in pharmacies nationwide for use with Humalog® (insulin lispro injection [rDNA origin]), the most-prescribed mealtime insulin in the United States.

Lilly also announced today that it will launch an insulin pen that delivers Humalog in smaller increments, HumaPen® LUXURA™ HD, in April 2007. LUXURA HD is a reusable pen that can deliver from 1-to-30 units of Humalog in half-unit increments, beginning after the first unit. This type of pen may be attractive to people with diabetes that do not need large amounts of insulin, or parents of some children with diabetes. LUXURA HD will require a prescription.

Insulin pens were developed on the premise that delivery devices that are more acceptable to patients could improve patient compliance and make a positive contribution to long-term diabetes control.1 Unlike traditional insulin pens or vial and syringe, MEMOIR doesn't resemble a medical instrument. MEMOIR, which is reusable, is sleek and designed to resemble a writing pen, enabling the potential for more discreet injections in public compared to using a vial and syringe.

In a clinical study of experienced pen users, 81% of patients preferred MEMOIR over the pen they were using before joining the study. MEMOIR was considered easier and more convenient to use than the pre-study pen and rated higher for certain pen features and most tasks related to dosing. MEMOIR was developed in partnership with Battelle Medical Device Solutions, a leader in device innovation based in Columbus, Ohio.

Of the 21 million people with diabetes in the United States, more than four million currently use insulin to help manage their blood sugar.

"I see real advantages in a new tool such as MEMOIR that remembers recent insulin doses, including the priming doses. The daily routine of balancing meals and blood sugar readings with multiple insulin injections can be cumbersome and overwhelming for patients," said Linda Siminerio, PhD, assistant professor of medicine and executive director, University of Pittsburgh Diabetes Institute. "Anything that helps simplify the management of this disease and puts patients in a better position to self-manage is beneficial."

"As a busy college student, I'm not always thinking about how much insulin I took at my last meal," said Reuben Bresler, a 20-year-old from Columbus, Ohio, with type 1 diabetes and one of the first people in the U.S. to receive a MEMOIR pen. "MEMOIR helps me keep track of my insulin doses if I forget whether I've taken it - or how much I took. I also like that it looks like a writing pen instead of a medical instrument. I can just take it out, use it and not feel self-conscious."

Patient Needs Drive Innovation in Device Technology

Precise meal-by-meal blood sugar management is important in diabetes management. However, despite new treatment options that have become available during the past few years, the American Diabetes Association's recommended blood sugar goal - an A1C level of less than 7% - remains elusive for many with diabetes (A1C is a measure of average blood glucose levels over a two-to-three-month period). Fewer than half (43%) of Americans who have been diagnosed with and are being treated for diabetes are actually achieving this A1C target. [Editor note: as my 2006 year-end review indicates, this is a slight misrepresentation of the data. Although the actual number is correct, as the Quest Diagnostics Health Trends™ Diabetes Report indicates, among patients who regularly see their doctors and have hemoglobin A1C's done by a lab, control has actually improved.]

To understand current behaviors and how specific pen features could help patients manage their diabetes, Lilly sponsored a national, 1,000-person telephone survey of people with diabetes who inject insulin at least once a day. The survey, conducted by Kelton Research in January 2007, showed that, not surprisingly, respondents were interested in new tools that could help them better manage their disease:

Memory can help

-- Two-thirds of respondents said a reusable pen that tracks the date, time and dose of insulin would be valuable.

-- One-third of patients reported that they forgot whether they took their insulin dose at least once a month; of these, 84% said a memory feature would be valuable.

-- More than 9 in 10 (94%) said it is important to know if they missed an insulin dose

Looks matter too: Style and design considerations

-- 58% of those surveyed said they would be interested in using an insulin delivery device that looked like a writing pen instead of a medical instrument.

-- More than four in 10 said that a stylish looking pen would make them feel more comfortable injecting insulin in a public place.

"Individuals with diabetes face unique challenges in managing this highly complex and personal disease. Practical and innovative solutions such as Lilly's new MEMOIR pen can help ease the management of diabetes at mealtimes," said Matt Beebe, Humalog brand team leader, Lilly USA. "Our goal is to help patients more accurately and discreetly manage their use of mealtime insulin such as Humalog."

Lilly continues to develop new insulin delivery devices to meet the needs of people with diabetes. To learn more about Humalog and HumaPen MEMOIR, visit Humalog.com.

Indication

Humalog is for use in patients with diabetes to control high blood sugar and should be used with a longer-acting insulin, except when used in combination with sulfonylureas in patients with type 2 diabetes.

Important safety information for Humalog

Humalog should not be used during episodes of hypoglycemia and in patients sensitive to Humalog or one of its excipients. Safety and effectiveness in patients less than three years of age have not been established. There are no clinical studies of the use of Humalog in pregnancy or nursing mothers. Potential side effects associated with the use of all insulins include low blood sugar, weight gain, low blood potassium, changes in fat tissue at the site of injection, and allergic reactions, both general and local. Starting or changing insulin therapy should be done cautiously and only under medical supervision.

Humalog starts working quickly because it is absorbed quickly. That's why you should use it at mealtime and take it within 15 minutes before or immediately after your meal. Because Humalog is a mealtime insulin, you may also need a longer-acting insulin to get the best blood sugar control (except when using an insulin pump).

For complete user instructions for HumaPen MEMOIR, please refer to the full user manual provided with the pen. Humalog, HumaPen MEMOIR and HumaPen LUXURA HD require a prescription.

For additional important safety information, visit http://www.humalog.com.

About Diabetes

According to the Centers for Disease Control and Prevention, diabetes affects nearly 21 million Americans; of that, nearly one-third, or approximately six million people, do not know they have the disease. Diabetes is the sixth leading cause of death in the United States and costs approximately $132 billion per year in direct and indirect medical expenses.

About Lilly Diabetes

Through a long-standing commitment to diabetes care, Lilly provides patients with breakthrough treatments that enable them to live longer, healthier and fuller lives. Since 1923, Lilly has been the industry leader in pioneering therapies to help health care professionals improve the lives of people with diabetes, and research continues on innovative medicines to address the unmet needs of patients. Lilly also strives to recognize the personal and professional contributions of those with and without diabetes through the annual LillyforLife™ Awards. For information about the Awards program, visit www.lillyforlife.com. For more information about Lilly's diabetes products, visit http://www.lillydiabetes.com.

About Eli Lilly and Company

Lilly, a leading innovation-driven corporation, is developing a growing portfolio of first-in-class and best-in-class pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Ind., Lilly provides answers - through medicines and information - for some of the world's most urgent medical needs. Information about Lilly is available at http://www.lilly.com.

Humalog® is a registered trademarks of Eli Lilly and Company. HumaPen® MEMOIR™ and HumaPen® LUXURA™ HD are trademarks of Eli Lilly and Company.

Article URL:
http://www.medicalnewstoday.com/medicalnews.php?newsid=65096

Successful Islet Cell Transplant Without Immunosuppressive Therapy In Mice With Type 1 Diabetes

This was another interesting article which incorporates some of the issues identified in my post this weekend, this one coming from researchers in New York.

Successful Islet Cell Transplant Without Immunosuppressive Therapy In Mice With Type 1 Diabetes
Medical News Today
Mar 12, 2007

Scientists at Weill Cornell Medical College may have reached a breakthrough in the search for a lasting cure for type 1 diabetes.

Reporting in the Feb. 20 issue of the Proceedings of the National Academy of Sciences, the team greatly boosted the number of immune T-cells able to shield transplanted pancreatic islet cells from attack by the immune system. Insulin-producing islet cells are deficient in type 1 diabetes.

"If we can replicate this in humans, we might someday do away with the lifelong use of powerful immunosuppressive drugs that patients must take after islet cell transplant -- drugs that we believe also do harm to islet cells over time," explains the study's senior author Dr. Manikkam Suthanthiran, chief of the Division of Nephrology and Hypertension at Weill Cornell Medical College and chief of the Department of Transplantation Medicine at New York-Presbyterian Hospital/Weill Cornell Medical Center.

Type 1 diabetes is an inherited disorder in which the body's immune cells attack islet cells in the pancreas, reducing or eliminating the body's ability to produce the blood-sugar hormone. It is distinct from the much more common type 2 form of diabetes, where obesity and other factors cause a gradual decline in cells' sensitivity to insulin.

Scientists have sought to reverse type 1 diabetes by transplanting new islet cells. The procedure has met with some success -- in fact, Dr. Suthanthiran's team at New York-Presbyterian/Weill Cornell performed the first successful islet transplantation in the tri-state area in patients with type 1 diabetes in 2004.

However, problems remain. "To stave off the destruction of transplanted cells, patients must be placed on lifelong immunosuppressive therapy," Dr. Suthanthiran explains. "Besides having powerful side effects, we're learning that these drugs can be toxic to islet cells, too."

Now, an innovative biochemical manipulation of immune cells may get around that problem.

Working in collaboration with researchers at The Rockefeller University, the research team focused on immune system regulatory T-cells (T regs). These cells help the immune system decide which entities are "enemies" and which are "friendly" and should be left alone.

"Specifically, there are a subset of T-cells with cell-surface proteins CD4 and CD25, which are called natural regulatory T-cells," Dr. Suthanthiran explains. "These cells express a key factor called FOXP3, and the CD4+CD25+Foxp3+ regulatory T-cells suppress the runaway immune response to islet cells. Without Foxp3, the suppression of the islet destructive response cannot take place."

Unfortunately, Foxp3-positive T-cells make up a paltry 2%-5% of the total T-cell population, so they have little impact in shielding transplanted islet cells from harm.

However, working with the standard mouse model for type 1 diabetes, the researchers were able to convert the much more common form of CD4+ CD25- T-cells into CD4+CD25+ T-cells that did express protective FOXP3.

"We did so by a two-pronged approach," Dr. Suthanthiran says. On the one hand, the research team exposed the much more common form of CD4+ CD25- T-cells to transforming growth factor-beta (TGF-b), which helps switch the T-cell over to a Foxp3 expressing cell.

But TGF-b on its own is too blunt an instrument.

"If we turn all of these T-cells into random immune suppressors, that could lead to more cancers and other problems," the researcher explains. "So, we used another immune system signaler, the dendritic cell, to target Foxp3 activity much more specifically and shield only the islet cells from immune system attack."

Study co-researcher Dr. Ralph Steinman of The Rockefeller University actually discovered the dendritic cell and its role in immune system signaling, and was instrumental in this research, Dr. Suthanthiran says. Dr. Steinman's group has shown that dendritic cells are highly efficient in turning on natural regulatory cells into islet protective cells.

"When CD4+ CD25- T-cells came into contact with both TGF-b and the specific antigen-presenting dendritic cells, they switched over to the immunosuppressive FOXP3 variety," he says. "The dendritic cells made sure that this protective immunosuppression was targeted to islet cells, specifically."

The result: successful islet transplantation in diabetic mice without any pharmacologic immunosuppression; the transplanted islet cells stayed healthy and produced insulin over the full nine weeks of the study.

And there was a bonus: "We also determined that this approach shields the pancreas' own islet cells from harm," the researcher says. "That's important, because newly diagnosed type 1 diabetes patients often have some percentage of working islet cells remaining. This strategy might protect those cells, as well as the transplanted cells."

According to Dr. Suthanthiran, there's no reason to believe this approach wouldn't also protect other types of transplanted cells or organs, including lung, kidney and hearts transplants.

"It's also important to note that we were treating established diabetes in this mouse model," Dr. Suthanthiran says. "Most of the success so far has been in preventing disease before it sets in, but this is akin to going into a house and putting out the fire after it has already started."

Of course, it remains to be seen if success in mice will translate to success in human type 1 diabetes. But Dr. Suthanthiran says he is optimistic.

"We want to create a transplant situation where we don't have to deliver any outside immunosuppressive drugs," he says. "That would truly be the best kind of cure."

This work was funded by the American Society of Transplantation, the Juvenile Diabetes Research Foundation and the U.S. National Institutes of Health.

Co-researchers include lead author Dr. Xunrong Luo, formerly at Weill Cornell Medical College, now at Northwestern University, Chicago; Dr. Hua Yang and Dr. Ruchuang Ding of Weill Cornell Medical College; Samantha L. Bailey and Kathryn Pothoven of Northwestern University; and Dr. Kristin V. Tarbell (co-lead author) and Dr. Ralph M. Steinman of The Rockefeller University, New York City.

Weill Cornell Medical College

Weill Cornell Medical College -- located in New York City -- is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine. Weill Cornell, which is a principal academic affiliate of New York-Presbyterian Hospital, offers an innovative curriculum that integrates the teaching of basic and clinical sciences, problem-based learning, office-based preceptorships, and primary care and doctoring courses. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research in such areas as stem cells, genetics and gene therapy, geriatrics, neuroscience, structural biology, cardiovascular medicine, AIDS, obesity, cancer and psychiatry -- and continue to delve ever deeper into the molecular basis of disease in an effort to unlock the mysteries behind the human body and the malfunctions that result in serious medical disorders. Weill Cornell Medical College is the birthplace of many medical advances -- from the development of the Pap test for cervical cancer to the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., and most recently, the world's first clinical trial for gene therapy for Parkinson's disease. Weill Cornell's Physician Organization includes 650 clinical faculty, who provide the highest quality of care to their patients.

New York-Presbyterian Hospital
425 East 61st St., Fl. 7
New York, NY 10021
http://www.nyp.org

Article URL: http://www.medicalnewstoday.com/medicalnews.php?newsid=64976

Penn Researchers Identify New Molecular Path To Fight Autoimmune Diseases

Type 1 diabetes, rheumatoid arthritis and multiple sclerosis are a few of the different autoimmune diseases that are aggravated when a certain type of white blood cell (the immune regulatory cell) fails to work properly. A cause of this malfunction in humans is when a mutation in the FOXP3 gene disables the immune cells' ability to properly function, in effect, disabling the immune system's ability to identify self vs. non-self. Although FOXP3 has been known about for several years, the manner that it functions was not. But in a brand new study published online in the Proceedings of the National Academy of Sciences, researchers at the University of Pennsylvania School of Medicine have apparently discovered a way to modify how enzymes act on the FOXP3 protein, in essence, enabling them to re-educate how the regulatory immune cells actually work. It is possible that these findings could have dramatic implications for treating a variety of different autoimmune diseases, including type 1 diabetes.

"We have uncovered a mechanism by which drugs could be developed to stabilize immune regulatory cells in order to fight autoimmune diseases," says senior author Mark Greene, MD, PhD, the John Eckman Professor of Pathology and Laboratory Medicine. "There's been little understanding about how the FOXP3 protein actually works." First author Bin Li, PhD, a research associate in the Greene lab has been working on elucidating this process since FOXP3's discovery almost 5 years ago.

Li discovered that the FOXP3 protein works via a complex set of enzymes. One set of those enzymes are called histone deacetylases, or HDACs. These enzymes are linked to the FOXP3 protein in association with another set of enzymes called histone acetyl transferases that modify the FOXP3 proteins.

Li found that when the histone acetyl transferases are turned on, or when the histone deacetylases are turned off, the immune regulatory cells work better and longer. As a consequence of the action of the acetylating enzyme, the FOXP3 protein functions to turn off pathways that would lead to autoimmune diseases.

"I think this simple approach will revolutionize the treatment of autoimmune diseases in humans because we have a new set of enzymatic drug targets as opposed to the non-specific therapies we now use," says Greene. Non-specific therapies include the use of steroids and certain chemotherapy-like drugs that act on many cell types and have significant side effects.

"Before this work, FOXP3 was thought essential for regulatory T-cell function, but how FOXP3 worked was not known," says Li. "Our research identifies a critical mechanism. Based on this mechanism, treatments could be developed to modulate this regulatory cell population."

"In this line of investigation, we have learned how to turn on or off this regulatory immune cell population - which is normally needed to prevent autoimmune diseases - using drugs that are approved for other purposes, but work on these enzymes" notes co-author Sandra Saouaf, PhD, a research associate at Penn.

Li, Greene, Saouaf and Penn colleagues Wayne Hancock and Youhai Chen are now extending this research directly to several mouse models of autoimmune diseases.

Source:

Bin Li, Arabinda Samanta, Xiaomin Song, Kathryn T. Iacono, Kathryn Bembas, Ran Tao, Samik Basu, James L. Riley, Wayne W. Hancock, Yuan Shen, Sandra J. Saouaf, and Mark I. Greene; "FOXP3 interactions with histone acetyltransferase and class II histone deacetylases are required for repression"; PNAS published March 7, 2007, 10.1073/pnas.0700298104 (Immunology).

http://www.pnas.org/cgi/content/abstract/0700298104v1

Health Findings From Institute To Be Free Online

The following was posted in this morning's Washington Post, and is what I would describe as a major victory for U.S. taxpayers. At present, the results from the $600 million spent on biomedical research studies at the Howard Hughes Medical Institute, even those funded by the National Institutes of Health (NIH), have not always been made readily available to taxpayers. However, there has been pressure to change this and it looks like taxpayers have scored a recent victory.

Some relevant background info: As you may be aware, research activity at NIH is divided into two parts: the "extramural" parts consist of funding of biomedical research outside of NIH, while the "intramural" parts of NIH conduct research within the 27 "institutes" that comprise the NIH. The biggest issue has been with extramural research, as this is funded by taxpayers even though the actual research is done elsewhere, but the results of this research has not always been made available to taxpayers. A major recipient of NIH extramural research dollars has been the Howard Hughes Medical Institute (HHMI).

The HHMI is a U.S. non-profit medical research institute originally founded by the aviator and engineer Howard Hughes in 1953. Initially, the institute was formed with the stated goal of basic research including trying to understand, in Hughes' words, "genesis of life itself". However, despite its lofty objective, in the early days, HHMI was seen as being a tax haven for Hughes' huge personal fortune.

In 1976, Howard Hughes died in without a will. Following a number of lengthy court proceedings, the HHMI received huge sum of money from the Hughes fortune enabling it to dramatically increase its research budget. During that same period, HHMI refocused its mission primarily on genetics, immunology and the rapidly growing field of molecular biology. The work in immunology holds a great deal of interest to patients with type 1 diabetes since it is an autoimmune disease.

To date, HHMI has only selectively made available its research results, even that which is funded by U.S. taxpayers. The NIH has been pressuring HHMI to release the results of the studies it has funded, and today, HHMI finally agreed to do just that. Even more compelling, however, is that Sen. John Cornyn (R-TX) is expected to reintroduce legislation that would require free posting of all government-funded research. Congress has been considering adding that requirement to the National Institutes of Health appropriations bill.

Regardless, this article was in today's Washington Post, and may be of interest.

Generic Insulin Could Save $797+ Million According to Express Scripts Study

According to a recent study (see HERE) undertaken by pharmacy benefits manager Express Scripts Inc., some estimates of the potential savings generated by the pending bill now in Congress (S. 623/H.R. 1038, the "Access to Life-Saving Medicine Act of 2007") on prescription expenditures have been forecast. As part of that study, the potential savings on insulin has also been computed. Although the savings for generic insulin is factored into the savings calculation, out of an estimated total of $71 billion in savings over 10 years that the Express Scripts report found, the study assumes that biggest savings will come from anemia treatments, followed by human growth hormones, then treatments for MS, with insulin generating the least savings of the drug classes examined. When the other treatment categories are subtracted from the total estimated savings, the relative savings for insulin is comparatively small, but still noteworthy at $797 million in the first year, and totaling in excess of $16 billion over 10 years! Another study was done for the Pharmaceutical Care Management Association (PCMA), which represents pharmaceutical benefit managers, reached a similar conclusion on the potential for savings that this legislation might create, although their study did not disclose savings by drug class.

As might be expected, the Biotechnology Industry Organization (BIO), which represents such companies as Novo Nordisk, Eli Lilly and Company and Sanofi Aventis immediately disputed the Express Scripts estimates, adding that they doubted the validity of both the Express Scripts study and the PCMA study.

"As a result of numerous flawed assumptions, and the lack of any credible evidence to support these alleged savings, we believe these studies should be rejected as unscientific and unreliable," stated BIO President and CEO Jim Greenwood.

A closer look at the "flaws" cited indicates that the claims BIO is making are no more convincing than the the Express Scripts study, suggesting that the debate is really little more than arguments being made by a trade group who is trying hard to prevent any competitors from entering the market.

In a similarly predictable response, Kathleen Jaeger, the president and chief executive of the Generic Pharmaceutical Association, said that even if generic biologics were only 25% less than their brand-name counterparts, it would be a huge savings for consumers.

The underlying assumptions of the Express Scripts study are as follows:

Express Scripts conducted the study by taking a 25% discount off brand-name medicines in four classes of drugs that would already have generic competition because of patent expirations if copycat biologics were allowed. Express Scripts decided on that discount because it said that the generic version of human growth hormone sells at a 25% discount to its brand name counterparts in Europe.

They also assume that 25% of patients on insulin would ultimately switch to generics, which seems to be a conservative yet realistic estimate, and is significantly smaller than the estimates that generics will capture for the other major drug classes evaluated. As I previously wrote, the reason is because although human insulin (basically, everything but analogs) still has a large share of total insulin sales, growth for human insulin formulations has essentially ground to a halt since the introduction of analogs, and their share is expected to show little if any growth for the foreseeable future. Of course, much of this is attributed to aggressive sales and the effort to migrate patients to more expensive, patented insulin analogs rather than any scientifically-proven clinical benefit. However, there is no denying that patients and physicians have adopted widespread use of insulin analogs and this study's conservative estimates appear to reflect this, as they show insulin analogs losing little if any market share to generics and most of the loss will come from Regular, NPH and 70/30 formulations. More details on the Express Scripts study can be reviewed here or here.

I think its clear that some savings will undoubtedly result from the introduction of generic insulin, the main question is how much? I believe that the Express Scripts study provides a conservative estimate for the potential cost savings we can expect to see on insulin assuming that this legislation is passed into law. Express Scripts substantiated their assumptions with the logic behind them. One of the "flawed" assumptions that BIO is citing is the presumption that a pathway under one law would generate savings for products approved under another makes the assumption invalid. But in the absence of having an approved pathway, Express Scripts had few other options other than to base their assumptions on the current pathway. Is it completely precise? No, but thats what make it an estimate! But the claims of flawed assumptions in the Express Scripts study made by Biotechnology Industry Organization (BIO) are really quite weak. Instead of trying to poke holes in sound studies and estimates, BIO would do far better to address some of its own industry's weaknesses, such as having its members develop a more precise methodolgy of actually dosing insulin. Every patient with type 1 diabetes knows that dosing insulin is as much an art as it is a science -- a complex and seemingly random theory of chaos guided by a handful of known variables. If BIO is really as concerned about patient safety as they claim, perhaps they would consider examining the safety record of existing insulins made by its own members, which are responsible for some 56,000 "adverse effects" requiring patient emergency room treatment each year, making it the medicine with the highest levels of adverse effects according to a recent Journal of the American Medical Association (JAMA) study.

Generic biotech drugs would be safe, cut costs, coalition says

Continuing the ongoing coverage I have given to the issue of legislation to support the introduction of generic insulin (including my original post, a follow-up based on NYT coverage, and the recent news that legislators have finally introduced a bill that would force the FDA to permit generic biopharmaceuticals where patents had already expired, as is the case with human insulin such as Humulin R and N or Novolin R or N), yesterday, several of the biggest private insurance providers were in Washington lobbying for support of the recently introduced legislation.

Generic biotech drugs would be safe, cut costs, coalition says
By Justin Blum, Bloomberg News
March 5, 2007

General Motors and Aetna were among companies that sent executives to Washington, D.C., on Monday to press for legislation allowing copies of medicines made from biotechnology as a way to reduce drug costs.

The companies planned meetings with White House aides and congressional staff to make a case that generic versions of gene-based biotech medications can be made safely. Biotech-drug makers are telling Congress that copies may pose health risks.

Generic biotech drugs could reduce prices by almost a third and cut into the profits of brand-name biotech companies such as Amgen and Genentech, analysts said. Some of the medications are among the costliest on the market and include treatments for cancer and arthritis.

"You can give great care but at a substantially reduced cost," Steve Miller, chief medical officer for Express Scripts, a manager of prescription-drug benefits based in Maryland Heights, MO, said at a news conference Monday in Washington.

The companies in the lobbying effort belong to the Coalition for a Competitive Pharmaceutical Market.

The group, which includes GM, the biggest U.S. purchaser of health care outside the government, says biotech generics would result in significant savings for companies that provide drug benefits for employees.

The company representatives will deliver their message on cost and safety in meetings at the White House and on Capitol Hill, coalition chairwoman Annette Guarisco, a GM executive, said in an interview.

The coalition also includes companies that make generic versions of conventional drugs, including Hospira and Barr Pharmaceuticals.

"Biogenerics represents a logical next step given the business we're already in," Edward Ogunro, a senior vice president for Hospira, said at the news conference.

Developing generic versions of some biotech medications might cost $10 million, compared with the $400 million to $800 million that brand-name manufacturers pay for the original versions, Ogunro said.

The Biotechnology Industry Organization, a trade association for biotech-drug makers, says the legislation could lead to sales of products that have harmful side effects and aren't as effective as the original version. The trade group made its case last month in a briefing for congressional staff.

U.S. law allows the Food and Drug Administration to approve generic versions of conventional drugs, made mostly through chemical synthesis, after their patents expire. There is no similar legal process for most biotech medicines, genetically engineered versions of human proteins such as insulin or growth hormone.

House and Senate members introduced legislation last month that would for the first time routinely allow copies of medicines made using biotechnology. Sponsors of the measure include U.S. Rep. Henry Waxman, D-CA, and Sen. Hillary Clinton, D-NY.

Biotech drugs generated revenue of about $32.8 billion, or 13% of the $251.8 billion in prescription sales to U.S. pharmacies in 2005, according to market-research firm IMS Health.

Generic versions of biotech medications may lower prices by 20% to 30%, according to Citigroup.

Companies that pay for insurance plans are eager to find ways to reduce costs of biotech medications, said Steven Meholic, head of pharmacy management for insurer Aetna.

"It's something our customers are very focused on," Meholic said.

URL for this article:
http://www.bloomberg.com/apps/news?pid=newsarchive&sid=afymxnDNIGXs