Thursday Update

It's been a while since I posted anything with a lot of substance, but work has been keeping me pretty busy lately and travel plans for the Memorial Day weekend kept me away from my computer for a few days when I might otherwise have blogged. Anyway, there's been a lot of chatter about the nomination of Judge Sonia Sotomayor for the U.S. Supreme Court. She has lived with autoimmune-mediated type 1 diabetes since age 8, and I can't really add much to what's already been said about this, but the reality is that it SHOULD be a non-issue. I guess we have a way to go before we can honestly say that diabetes should not prevent anyone from accomplishing their goals, because if that were really true, the press wouldn't keep mentioning it, would they? Maybe someday ...

DiaKine's Lisofylline (LSF) Heads to Trial ... Combo Trials Still Pending

Last year (in May 2008), a partnership was announced for the next phase of INGAP (see here for more background on that, and see the Press Release for the combo trials at https://web.archive.org/web/20130902071938/http://diakine.com/assets/news20090512.pdf). Those trials would test a new combination therapy, consisting of Kinexum/Exsulin's INGAP peptide (which has since been re-branded Exsulin) and DiaKine's anti-inflammatory drug Lisofylline (LSF), and the trials were expected to begin in late 2008, but have apparently been delayed.

Josh Levy's blog has a good overview of the pending Phase 1 human clinical trial for the DiaKine's Lisofylline (LSF) which is meant to to arrest the errant immune response that causes type 1 diabetes. He writes:

"The combination had already given good results in NOD mice. That trial was supposed to start in "late 2008". Kinexum Metabolics has since changed it's name to Exsulin (not INsulin, but EXsulin. Get it?) I can't find any record of the LSF+INGAP trial starting, but each company is testing it's own stuff seperately, so maybe after that, they'll test them together."

Anyway, the first phase of the LSF trials are now underway (well, they begin in June 2008). Note that this is a Phase 1 clinical trial, and it's SMALL, involving a mere 8 people, so I'll contain my excitement for a while. However, as you may have already gathered, the folks at DiaKine (and Exsulin) are closely affiliated with Eastern Virginia Medical School's Diabetes Institutes Foundation and the Strelitz Diabetes Institute, so if the DiaKine drug works as hoped, there are definitely plans to then combine this autoimmunity treatment with INGAP (see here for more background on that) to regenerate islets in those who have no islets remaining thanks to a faulty immune response. In theory, that would address the key elements (autoimmunity and beta cell replacement and/or regeneration) that most experts now believe are required to actually cure type 1 diabetes (the consensus is that there will be several distinct components to any "cure").

It's still quite early, but the real hope is for the next step (assuming LSF works as expected) to try the combo therapy out on real patients with established type 1 diabetes (newly-diagnosed patients need not apply - an unusual change!), thus these trials (I guess we can't run before we can walk). What is not known (at least by me) is whether either or both legs of this treatment protocol would be required on an ongoing basis, and if so, how often, etc. However, I think we can safely conclude that this method of treatment would likely result in far better glycemic control than an artificial pancreas could, as the consensus seems to be that the algorithms in closed-loop systems are still are nowhere near as robust, and therefore will likely still require some patient input (such as entering a carbohydrate count for a meal) to function, as current CGMS sensors aren't functional enough to identify whether a blood glucose spike is coming, and if that is due to a meal, or something else, thus the need for patient input.

As I've noted before, "inflammation" treatments are a HOT area of research, in part, because there's currently not many targeted treatments for this (most treat ALL forms of inflammation, not one which which targets a specific type of body tissue or protein), but we should be seeing more in the not-too-distant future, including an CD-3 antibody treatment from the Eli Lilly & Co./Macrogenics partnership. So far, Novo Nordisk's Seattle investment hasn't yet yielded anything (its been in place for less than a year), and I suspect the company's investment was mainly because it didn't want to risk being left behind if any of these treatments prove fruitful, but I'm not expecting much to come from Novo, which clearly has a financial interest to keep churning out more insulin (and let's not forget incretins for type 2 diabetes, although the company's GLP-1 peptide liraglulitide (branded as "Victoza") has yet to get FDA approval. In any event, as far as inflammation treatments, you may recall that I have referred to a chart (see here) on drug category development over time that was created by Boston Consulting Group.

As I noted last year, we are entering a new era, and we may well see more inflammation treatments, possibly several different ones, which may one day present doctors with a choice of how best to arrest autoimmune attacks which cause type 1 diabetes. All of this is exciting stuff, but I should note has been in the pipeline for some time now, so its nice to see a steady progression.

What else?

Hmmmm, let's see ...well, there is some relevant news on the Federal Agency I love to hate most, the U.S. FatalFood and Drug Administration/FDA (if you look back to my posts throughout the last year, you'll find plenty of evidence why I feel this way). The good news, for a change, is that recent FDA news actually seems positive!

An important leadership change at the FDA has been long overdue, but already, we're seeing the first example, highlighted in an editorial published on Tuesday in The New England Journal of Medicine relative to the U.S. Food and Drug Administration (FDA).

The recently-approved new FDA Chief Dr. Margaret "Peggy" Hamburg and her colleague, FDA deputy commissioner Joshua Sharfstein, wrote that the agency's success shouldn't be measured by the number of drugs approved, or the number of facilities inspected. Instead, they assert, that the agency's success should be measured by its ability to promote public health. Good, at least they have their priorities right. The last FDA chief left and in his parting e-mail, he wrote to FDA employees to take the FDA back!

According to the Hamburg/Scharfstein leadership team, the ability to promote public health means that the agency should use its regulatory powers more aggressively, and I hope that proves true. The agency has demanded little from the pharmaceutical and biotech industries in terms of post-marketing analysis, and far too many drugs have later proven dangerous. We can cite Vioxx and the type 2 diabetes medication Avandia as two prominent examples, but there are surely countless others which haven't been identified because we don't systematically gather aftermarket data, generally.

The new FDA leadership have their work cut out for them. In recent years, the FDA's role in promoting public health has been badly tarnished. I have chronicled the agency's repeated failures, which range from bad drugs, biopharmaceuticals, shady clinical trials, cover-ups, to food-borne illness outbreaks. The FDA has been criticized by even it's own employees, as putting the interests of industry ahead of public safety, and there have been repeated examples where the FDA was too slow to halt problems even once discovered. What's more, the agency has been accused of making decisions based on political considerations, rather than based on science (consider the the repeated delays of the Plan B "morning-after" pill, an emergency contraceptive), and accusations of getting too cozy with industry, with many of the agency's key positions filled by drug industry people who have a fiduciary responsibility for drug company shareholders, rather than subject matter experts, although rules on share ownership were supposed to resolve that issue, one must question whether someone with friends in the industry is really any less biased than someone without stocks in those companies.

Dr. Sharfstein, who has been acting commissioner since March 30, said last week he was eager for Dr. Hamburg to take over (one can't really blame him). During his very brief tenure, he's dealt with numerous problems, including voluntary recalls of pistachio products and a widely-sold antipsoriasis drug; problems with an independent review board that had been overseeing patient safety in hundreds of clinical trials; and of course, the outbreak of swine flu.

Perhaps more than anything, however, the morale at the FDA is in the dumpster. Last year, an anonymous website established by current and former FDA staff members called Thoreau-FDA.com that was highly critical of the agency and, in particular, former FDA commissioner Andrew von Eschenbach, who was accused of oppressing FDA employees and preventing them from doing their jobs properly. The website, which is anonymously crafted, was allegedly the brainchild of an unknown number of current and former agency employees.

Incidentally, in their editorial, Drs. Hamburg and Scharfstein admit they walk a tightrope between approving drugs/medical products too slow and preventing new treatments from reaching patients who need them and too fast and harming people in the process. But the focus has been on expediency in recent years, with the staff at the FDA ballooning in new drug approvals, with almost no new staff (in fact, a reduction) in the staff responsible for post-marketing analysis. In addition, there is a cloak of secrecy, with clinical trial results submitted to the FDA never released in order to protect the pharmaceutical industry. In their editorial, the new FDA leadership acknowledges this to some extent:

"Transparency is a potent element of a successful strategy to enhance the work of the FDA and its credibility with the public. Whenever possible, the FDA should provide the data on which it bases its regulatory decisions and other guidance and explain its decision-making process to the public."

Perhaps the clinical trial results will be made available to the public after some period of time as the European Medicines Agency (EMEA) does. There is even talk of addding new fees (on the industry) to facilitate post-market analysis, which could help clean up an industry which has effectively "cleaned up" financially, largely at taxpayer expense, in recent years with such corporate welfare programs as the Medicare Drug Benefit which was signed into law a few years ago.

Obviously, these two have their work cut out for them, and there's now talk in Congress of having the FDA regulate tobacco, too, as if they needed anything else to worry about?! Anyway, at least we can see subtle signs of a culture shift at the FDA, and this is a critical but positive sign.

Should We Be Questioning the Current Leadership at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)?

In other government-related news on diabetes, I have to admit that I'm not really a big fan of the current leadership for the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), which is one of the National Institutes of Health (NIH). The current Director is Dr. Griffin P. Rodgers, who was named as the ACTING Director of the NIDDK in March 2006, and about a year later, was named as Director.

My main reason is because he is leading an Institute that addresses medical specialties which are not related to his own medical training and education, yet he is responsible for leading an institute responsible for research impacting the health of millions of lives. His own background is NOT endocrinology or nephrology (although he IS board certified in Internal Medicine), his specialty is hematology (the study of the blood). Based on that, he would be a far better fit for the NIH's National Heart, Lung, and Blood Institute. However, I question whether he's the best choice to lead the Institute that is responsible for Diabetes and Digestive and Kidney Diseases.

He may well be an effective administrator, but he's really not a suitable replacement for the previous leader, Dr. Allen M. Spiegel, who was an endocrinologist, but since no one else was clamoring for the job and he was willing to take over on an interim, he got it. We really need to have a leader for this organization who specializes in the activities the NIDDK funds, not a completely different medical specialty. After all, its not really appropriate for an oncologist to be leading a dermatology organization, unless it pertains specifically to skin cancer! The same is true here. What's more, the NIDDK's participation in cross-Institute research, such as the NIH Autoimmune Diseases Coordinating Committee (ADCC) is, from what I can tell, virtually non-existent, even though a cure for type 1 diabetes is very much contingent on research into autoimmunity, and the NIDDK could benefit by becoming an active participant.

Now, keep in mind, as a government agency, its not like Dr. Rodgers can radically shift the direction of the NIDDK. Have a look at the NIDDK's annual report of sorts, the NIDDK "Recent Advances & Emerging Opportunities", and you can get an idea of where the Institute is going. But with news that the type 1 incidence estimate that is so often cited "5% to 10%" is not based on quantifiable fact, and JDRF and the ADA have started to use the 10% figure exclusively, an acknowledgment that the CDC confirmed with the (jointly funded with JDRF) SEARCH for Diabetes In Youth study proved that estimate was too small, even with the rapid growth in type 2 diabetes diagnoses, we are entitled to someone who is reasonably familiar with the disease etiology to be leading the Institute. Also, there's new evidence from the Lancet medical journal that the number of European children under 5 with type 1 diabetes could double by 2020. It is expected this is indicative of what is happening in North America, too. In a commentary, Dr. Dana Dabelea of the University of Colorado in Denver wrote:

"I think that these data from Europe are telling us what is going to happen in the United States. We know is that these rates don't seem to be increasing because of genetic susceptibility." Dabelea said. She also said in a telephone interview that Europe has very good data on diabetes but good statistics on the rate of type 1 diabetes are lacking for many countries, including the United States. (The U.S. Centers for Disease Control [CDC] and the National Institutes of Health do track the incidence of diabetes, but both fail to track by diabetes TYPE, so they must rely upon estimates derived from other research.)

Regardless, we should remember that the Institute IS responsible for administering the Special Statutory Funding Program for Type 1 Diabetes Research. Also, the NIDDK has been responsible for many groundbreaking research findings advancing the understanding of both type 1 and type 2 diabetes, and it strikes me as peculiar why we have a blood specialist running a diabetes and kidney research institute, we should have a subject matter authority running that particular Institute. Other Institutes in the NIH have people who specialize in their respective fields, so why doesn't the NIDDK? Surely, we should have someone with more direct expertise running the NIDDK so that person can effectively advocate for budgets, priorities, etc.

If you agree with me, write to your Congressman/woman. You can locate these people at http://www.usa.gov/Contact/Elected.shtml.

Anyway, that's all for the moment. I have lots of subject matter for future topics, and when time permits, I'll post them. For example, there's a group to push CVS/Caremark to properly package insulin in temperature-controlled packaging, which they aren't doing now ... I had my own Caremark nightmares a while back, but new healthcare plans have kept that in a constant state of flux. Luckily, I don't anticipate having to deal with Caremark for the next 12 months, but the subject is still ripe for advocacy. Anyway, I'll be back, but I can't promise exactly when!

Regards!