Possible Cures for Type-1 in the News (April)

LCT Will Start Phase-II Clinical Trials in New Zealand
LCT Publishes results from Phase-I Clinical Trials in Russia
Background: http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials#DiabecellbyLivingCellTechnologies
Blogging: http://cureresearch4type1diabetes.blogspot.com/search/label/LCT

Two pieces of good news from LCT, who are trying to cure type-1 diabetes by implanting encapsulated pig beta cells.  First, they have got permission from New Zealand to start a phase-II clinical trial.  Second, they published 18 month follow up results from the eight patients they treated as part of their phase-I trial in Russia.

Phase-II Permissions
Basically, they are half way done with their New Zealand phase-I study, but they can now call the second half the start of a phase-II study.  There is a clear progression here.  The first guys in Russia got about 5ku/kg, while the second half got 10ku/kg.  The first half of the New Zealand patients also got 10ku/kg, but the second half (the phase-II part) are getting 15ku/kg.  Right now, they have 8 patients as part of the Russian phase-I and 4 more as part of the New Zealand phase-I.  The second half of the New Zealand trial (the phase-II part) is 4 patients.  I don't think that is even close to enough people to finish a phase-II.  (80 or more people is normal for a phase-II.)  But it does get them started. And milestones are all about getting things started.

Congratulations to LCT for moving from phase-I to phase-II clinical trials!

Phase-I Results
I'm sorry that I don't have time to discuss their results, but I don't think they are radically different from the previously released data.

Press release: http://www.news-medical.net/news/20100330/LCT-receives-approval-for-New-Zealand-Phase-II-human-trial-of-DIABECELL.aspx
Clinical Trial Record: http://clinicaltrials.gov/ct2/show/NCT00940173


Atorvastatin (Lipitor) completes enrollment of Phase-II Trial

Background: http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials#AtorvastatinbyWilli

Blogging: http://cureresearch4type1diabetes.blogspot.com/search/label/Atorvastatin

Dr. Willi at Children's Hospital of Philadelphia is running an experiment where he gives Atorvastatin (Lipitor) to newly diagnosed type-1 diabetics.   I would summarize the rational behind this trial as "it worked in mice, and the drug is already approved, so let's try it".  This is the more official version from the study:

Preliminary studies have shown that members of the statin family of medications, including atorvastatin (Lipitor®), preserve beta cell function in a mouse model of type 1 diabetes. These finding suggest that use of atorvastatin in combination with insulin therapy may delay and potentially reverse the destruction of beta cells in patients who have recently developed type 1 diabetes. Atorvastatin (Lipitor®) is approved for use in adults and children (>10 years of age) who have elevated blood cholesterol levels. This study will examine whether atorvastatin (Lipitor®) may also help the body preserve insulin production in patients with newly diagnosed (within 8 weeks) type 1 diabetes.

In Feb 2010, this study finished enrolling patients.  This is important, because it is now possible to predict when they will finish collecting data.  (This study runs for a year, so they should have data collected by Feb 2011.)

More on GAD and Diamyd
I'm not big on posting links to other sites.  I figure if you want information from the net, you will go find it.  And since you know exactly what you want, and I don't, you will do a better job find links that you want to read, than I will.  However, I thought the link below was a particularly good overview of the history of Diaymd's drug (currently in phase-III trials - honeymoon only - and in the lead for eventual FDA approval):

http://www.diabeteshealth.com/read/2010/03/23/6611/the-story-of-gad/

My Web Page is Finally Updated
In addition to this blog, I have a web page where I try to keep status information on each treatment currently in clinical (human) trials.  However, this web page had gradually become out of date.  However, I have recently put a lot of time into updating it:
http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials

One of my major goals for this update is so that when I blog about a particular piece of research, I don't need to include basic information on that treatment.  Instead, I just have a link back to the web page, which describes how each treatment is expected to work.  You can see that philosophy in action, below.  Although I've made many improvements to the web page, it still has a ways to go.  Several of the descriptions of specific trials need more information and organization.


News on Animal Trials
Remember always: even successful animal trials usually don't result in human trials.  And even if they do, it is over 10 years from start of human trials to market approval, and none of the treatments discussed below have even started human trials, yet.

Leptin
Leptin is a hormone which has treated type-1 diabetes in NOD mice, and I've blogged on it before.  But the last time, I thought that an injection of leptin cured type-1 mice.  However, that was not true.  (My mistake.)  Instead, the mice were given a gene which caused them to generate their own leptin from that point onward, and they did not need insulin after that.   So the goal of this research is to use Leptin as a treatment for type-1 diabetes.  For mice it replaced insulin, but for people it might replace insulin or a combination of leptin and insulin might be a better treatment that insulin alone.  But in any case, leptin is being tested as a treatment for type-1 diabetes, not a cure.


I think the biggest news now is this paragraph:

Unger's team first asked permission to start human trials almost a year ago, he said. The hospital is prepared, they have an ample supply of potential volunteers, and they've lined up funding. What's holding the process up, Unger said, is getting the manufacturers of leptin to set up the logistics to guarantee the supply.

Usually, people are complaining about lack of money, not lack of drug.  So I think it is very likely that a clinical trial will start soon.  I know of one other Leptin study that has been running for years, (at Columbia) so maybe Dr. Unger's team can ask the Columbia team about their supplier. :-)


Newspaper: http://www.dallasnews.com/sharedcontent/dws/news/healthscience/stories/030210dnmetdiabetesstudy.1668e2147.html

I'm not sure that I will cover this moving forward.  It is interesting and unique and new, but I don't think it is a cure.

CureDM
These guys are working on a protein which stimulates the growth of beta cells (so much like Exsulin).  They cut a big deal with Sanofi-Aventis.  They will get millions of dollars, based on making development milestones, and (if successful) Sanofi-Aventis will market their new drug and pay royalties.   They hope to start human trials later this year.  The headline for this news article, which I think sums up the situation perfectly is this:  Sanofi-Aventis Places Large Bet on Diabetes Drug Candidate.

News article: http://www.medicalnewstoday.com/articles/185008.php
Press release: http://www.curedm.com/news/2010.04.08_curedm_press_release.pdf 

I do not think that simply growing more beta cells will -- by itself -- cure type-1 diabetes, because the broken immune system will attack the new beta cells same as the old.  But I do think it could be part of a cure: http://joshualevy.pbworks.com/ConceptsAndBackground#RegrowingBetaCells

New Cure in Mice (by Dr. Pere Santamaria)
Vaccine-like cure works in mice.  Remember: mice cures seem to be found about 4 times a year (over 145 so far), and so far none of these has led to a cure.  So this is good news, but not break-through news.

News article: http://www.businessweek.com/lifestyle/content/healthday/637852.html

I usually include a link to the abstract, and here it is:
http://www.cell.com/immunity/retrieve/pii/S1074761310001226
but it was so technical and dense that I had trouble understanding it, although it was written in English. 

Joshua Levy

All the views expressed here are those of Joshua Levy, and nothing here is official JDRF news, views, policies or opinions.

ToleRx Publishes Phase-II Data, 4 Year Follow Up

ToleRx In The News
Overview of what TolerRx is doing: http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials#OtelixizumabbyToleRx
Previous blogging: http://cureresearch4type1diabetes.blogspot.com/search/label/ToleRx

In January, ToleRx announced that their phase-III clinical trial of Otelixizumab was completely enrolled (which I previously reported on).  Now ToleRx has two more important pieces of information:

1. They are going to start a second phase-III clinical trial, called DEFEND-2.
2. Publishing 4 year follow up data on an earlier phase-II clinical trial (called TTEDD).

The second phase-III clinical trial is important because you need two successful trials for US FDA or EU EMEA approval.  So the sooner they start that second trial the sooner they can get approved. 

The 4 year follow up data is important, because it can tell us how well it works.  Remember that the goal of TTEDD was to determine the best dosing system for the phase-III trials, so we should expect better results from the phase-III trials, and lower side effects, then reported on here:

Treatment with ChAglyCD3 delayed the rise in insulin requirements of patients with recent-onset diabetes and reduced its amplitude over 48 months (+0.09 vs +0.32 U/ kg/ day in the placebo group). Using multivariate analysis this effect was correlated with higher baseline residual beta cell function and a younger age.

For an example of what this means,  if you assume a kid who weighs about 50kg, at the end of 4 years, they might have increased their insulin usage by about 16 units.  However, those that received the treatment only increased their usage by about 5 units.  Both went up, but the untreated patients went up a lot more.

Another issue for new drugs is safety, and here the news is good:

In this reported study, otelixizumab administration was associated with transient symptoms during dosing including flu-like syndrome and transient perturbation of Epstein Barr Virus (EBV).  During the 48 months of follow-up there were no EBV related symptoms, no higher incidence of infections, and no lymphoproliferative or other types of cancer observed.  Following the 18 month efficacy results of the present study, Tolerx has optimized the otelixizumab dosing regimen to minimize adverse events, with encouraging data on clinical effect.

Which I translate as: some people got flu like symptoms during treatment, but there were no long term side effects at all. Note that about 40 people were treated, and this was a 4 year follow up, so this will not close the book on safety issues, but it is clearly good news.

One interesting tid-bit is that the TTEDD study is not limited to honeymoon diabetics, although the follow on (DEFEND-1 and DEFEND-2) studies are.  Because the earlier study is open to non-honeymooners, but the later studies are not, I think it is reasonable to assume that this treatment did not work well for non-honeymooners.  However, it would interesting to see compare the TTEDD data for honeymooners vs. non-honeymooners.  The TTEDD study is still recruiting new patients.

Abstract: http://www.springerlink.com/content/p3572576j25l2640/
Press Release: http://www.prnewswire.com/news-releases/single-short-course-of-tolerxs-otelixizumab-provides-prolonged-preservation-of-beta-cell-function-87773937.html
Company Blog: http://www.tolerx.com/index.php?page=greenchair
Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT00451321

Joshua Levy
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF news, views, policies or opinions.

Possible Cures for Type-1 in the News (March)

Below are some generate updates on progress to a cure for type-1 diabetes, and other related news.  

LCT Gets Russian Approval for Encapsulation Technology 
LCT is in phase-I with their cure for type-1 diabetes, which is pig beta cells encapsulated so that the body's autoimmune attack can not get them.

LCT has received Russian government approval to market their encapsulation technology.  This approval does not cover the porcine beta cells inside LCT's encapsulation tubes, but it does cover the tubes themselves.  A future approval will be done for the porcine beta cells themselves.  This is continued strong progress towards LCT's stated goal of general availability of their treatment in Russia by 2011.


To put it bluntly, this puts LCT one approval away from being able to sell their treatment in Russia.  Now, at the moment, their treatment is not something that I would consider a cure.  However, I do believe that they will continue to improve their treatment, and I think it is possible that in 5, 10, or 20 years it will grow into something that I would consider a cure.


Note: whenever I blog about LCT, I get asked "how much will it cost?".  And the answer is: I don't know. LCT has not announced it, and it may not be decided as yet.  The whole idea of discussing the price of a treatment which you can not yet buy, for me, is putting the cart before the horse.  There are many other questions about this treatment that I think are more important, especially: what percentage of patients will be cured?  And, how long will the cure last?   Plus there is the issue of safety of something which has not gone through either US FDA or EU EMEA approval.
 

VUCCC
These guys published a press release recently, and so have been in the news.  The press release was issued because they filed to get patient on their technology.  The press release claims an 80% success rate but does not describe the treatment in any way.  They do say that whatever it is, it will be available commercially in Germany in 2010, and other places after that.

Personally, I'll be ignoring this press release, because I can not find a single study in the scientific literature, which reports on their treatment, or it's success rate.  I can't even find a reference to VUCCC prior to this press release.


press release: http://www.forbes.com/feeds/businesswire/2010/03/03/businesswire136160731.html

I'd like to thank Ellen for emailing VUCCC and posting their reply, which you can read here: http://islet.org/forum/messages/53711.htm
They make a number of claims which I find hard to believe.  For example: they started phase-I human trials in 1990.  They have completed phase-III trials (in 1996), and have since done two phase-IV trials (IV generally means more/new testing on already approved treatments) since then.  They claim to have cured outright ("disease free") over 10,000 people (none of whom have ever posted to a public forum, of course....) They claim to have three papers written (one in 1996, another in 2002, and the third 2006) just waiting for the patient so they could be submitted to "Nature or a Journal of similar stature".   So the authors of that first paper just sat on it for 14 years?


This is their description of their technology, starting with the fact that in type-1 diabetes, the body's own immune cells attack the body's own beta cells:

These haywire immune cells are produced by hibernating virus particles found in all Diabetics' islet cells. ... The goal of our treatment is to stimulate the islet cells to express these hibernating virus particles and enable the body to eliminate the cells carrying the hibernating particles once and for all which rids the body of these "bad" immune cells and replaces them with low physiological levels of inactive memory cells that can no longer attack the islet cells - thus stopping beta-cell damage and restoring proper immune function.

That first sentence about hibernating virus particles is nothing I've ever heard before, so I"m not tempted to put much faith in the rest.  (Plus it sounds like quack treatments I have heard of in the past.)  And without published results, faith and wishful thinking is really all there is.  But if anyone flies to Germany this year and gets cured, please do tell! :-)

INGAP/Exsulin Update
INGAP (now called exsulin) is a treatment that is undergoing phase-II human trials, and is hoped to trigger the body to regrow lost beta cells.

First, a couple of researchers have found a way to make rINGAP (recombinant INGAP).  The surprise was that rINGAP was approximately 100x as powerful as INGAP in test tube testing.  If borne out in live animal (and later human) testing, this would be even better news.  Exsulin has long complex history, so if you want more details, please ready my previous blog entries on it:
http://cureresearch4type1diabetes.blogspot.com/search/label/Exsulin

Abstract: http://www.ncbi.nlm.nih.gov/pubmed/19635567


Second, Exulin has started another round of phase-II clinical studies.  This is the study I had previously discussed here: 
http://cureresearch4type1diabetes.blogspot.com/2009/11/possible-cures-for-type-1-in-news-nov.html
The update is two fold: first, they started enrolling patients in Nov 2009, and second, they hope to complete the study by August 2010.


Clinical trial record: http://www.clinicaltrials.gov/ct2/show/NCT00995540


Change in Blogging Policy
My policy is to blog on research "in human trials now, or has been in the past, or is expected to be within the next two years" which is aimed at curing type-1 diabetes.   So in the past, I have included any research where the researcher claimed they would start a human trial within the next two years.  Unfortunately, many researchers claimed this, but never started a clinical trial, even after many years.  So I'm changing my policy, and will now only blog on research that has started the paperwork required to start a clinical trial (even if they have not yet quite started the trial itself).  So if they have started the paperwork for a phase-I trial, or submitted the US FDA's IND paperwork, or anything similar to that.  I also plan to drop coverage of any treatment which was in human trials, but has not been in human trials for a three year period of time.  I expect these policy changes to give me more time to focus on more promising research.

Reminder About Terminology
Remember that many words are used differently by professionals, than by the rest of us.  For example, if you ask people what it means to be a "honeymoon diabetic" most would say "Someone who was just recently diagnosed".  But if you asked a researcher that same question they would say "Someone who is still making their own insulin (as shown by a C-peptide test, for example)", and the two are not the same thing.

Also, "vaccine".  If you ask a bunch of random people what a "vaccine" is they would say "something which you give to healthy people to prevent them from getting a disease".  But a health professional uses a different definition that sometimes includes treatments given to people who are already sick.

In general, I use the definitions used by parents and patients.  The "general population" definitions, and not the health care professional's definitions.

Joshua Levy
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF news, views, policies or opinions.

Diamyd Combo Phase-II Trial Scaled Back

Back in Feburary 2009 I blogged on a very promising clinical trail that was combining the Diamyd treatment to stop the autoimmune attack and two drugs which were already approved for use in the USA.  This is an update for that research.

Diamyd Combo Phase-II Trial Scaled Back 


This Phase II study combines regenerative agents (lansoprazole and sitagliptin) and Diamyd. The regenerative agents are both marketed drugs in the US.  Diamyd is a vaccine like drug which trains the body's autoimmune system not to attack it's own cells.  Sitagliptin (Januvia) is a dipeptidyl peptidase-4 (DPP-4) inhibitor, and is used for type-2 diabetes.  Lansoprazole (Prevacid) is a proton-pump inhibitor (PPI) which prevents the stomach from producing gastric acid. The researchers hope that both lansoprazole and sitagliptin will help reverse beta cell damage or develop new beta cells.

This trial has been scaled back is a big way.  Originally, the researchers were hoping to screen about 160 people and include about 80 of them in the trial.  However, just after the study enrolled it's first patient, there was a major funding cut at NIH (the part of the US government were the study was being done).  At the same time, the primary investigator (Dr. David Harlan) got a new job at UMass at Worster, and so left NIH.  This double setback caused the study to shrink and be redesigned.  

Instead of 80 people in a placebo controlled, randomized trial, they ended up with 3 people in a pilot study where everyone was treated (so no control group).  Now the good news is that the trial is fully enrolled, so they will have all their data by October 2012.  However, the bad news is that the results will be hard to interpret (maybe impossible).  Because this study is using honeymoon type-1 diabetics, there is natural fluctuation in the amount of insulin used.   So with only 3 people and no control group, it will be hard to tell if any improvements are caused by the treatment or random fluctuation during the honeymoon.


Some Personal Opinions


Obviously, I'm hopeful that Dr. Harlan will restart this experiment once he gets settled at UMass Worster.  As far as I know this is the only clinical trail combining a treatment to control the autoimmune attack and a treatment to help the body generate more insulin.  I think combination like this represent one very promising approach to a future cure to type-1 diabetes. It's very disappointing to have it scaled back so much, and for reasons so unrelated to safety or effectiveness.

Clinical Trials site: http://www.clinicaltrials.gov/ct2/show/NCT00837759
NIH page: http://clinicalstudies.info.nih.gov/detail/B_2009-DK-0056.html
Unofficial Diamyd blog: http://diamyd.blogspot.com/

Joshua Levy
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF news, views, policies or opinions.

Possible Cures for Type-1 in the News (Feb)

Tolerx Completes Enrollment in Phase-III Otelixizumab Trial

On Jan 7, 2010 Tolerx announced that they had completed enrollment of their DEFEND-1 clinical trial. This is a phase-III study which is randomized, placebo-controlled and includes 240 patients at over 100 sites all over Europe and North America. Because each patient is followed for a year, we can expect results from this study after January 2011.

The study is designed to evaluate whether a single course of otelixizumab, administered to type-1 diabetics during their honeymoon phase, will preserve insulin production.

Otelixizumab targets CD3 receptor on a T cell.  The hope is that it will work in patients with type 1 diabetes who have residual beta cells by blocking autoimmune attack, while helping the "good" regulatory T cells that protect against the "bad" T cells, thus preserving the beta cells' ability to make insulin.

Press Release: http://www.prnewswire.com/news-releases/tolerx-completes-enrollment-in-defend-1-a-phase-3-type-1-diabetes-study-with-otelixizumab-80892467.html
Corporate Description: http://www.tolerx.com/index.php?page=trx4
Trial's Public Web site: www.DefendAgainstDiabetes.com

Diamyd Will Apply for Approval of Type-1 Treatment in 2011

Diamyd has announced that they expect to file the paperwork for market approval of their GAD65 targeted, type-1 treatment in 2011, after they complete the phase-III trials they have ongoing right now.  Obviously, the headline is great, but remember these things:

• No results from their phase-III trials have been released, yet.  They've got two different large phase-III trials going on right now.
  
• Applying for approval is great, but it usually takes a year or two to get it, after you apply.
  
• The current phase-III trials are all for honeymoon only, and so this approval will be for honeymoon only.
  

Even with all that, it would be great news to have something new approved for honeymoon type-1 diabetes. (Even if the short term result is likely to be just "uses less insulin" or "has longer honeymoon".)  Right now, we have nothing like that.  When they publish their phase-III results, we're likely to see how much of a cure this is likely to be, and for how many people.

Also, you might have seen a HULIQ headline "Approval of Diamyd's Diabetes Vaccine Set for 2011".  That's an outright mistake.  They expect to start the approval process in 2011, not finish it then.  The process takes a year or two to complete.

Press release: http://www.tradingmarkets.com/news/stock-alert/dmydf_swedish-diamyd-medical-to-apply-for-diabetes-vaccine-approval-2011-737987.html

Novo Nordisk Receives US Approval for Victoza (liraglutide) for the Treatment of Type 2 Diabetes 

This really isn't type-1 news by itself, but Liraglutide just got FDA approval, and this is the same drug that just started phase-II trials for type-1 diabetics, and that I reported on in January.  So there are now at least two drugs (the other is Byetta) which are approved for type-2s and causes them to generate more insulin.  If a treatment is found that ends the autoimmune attack, then these treatments might be paired with it to create a faster, more complete cure. 

I'm optimistic about this approach, because there are now four drugs in phase-III trials which are targeted at ending the autoimmune attack, and at least two already approved drugs,  another in phase-III trials, and several more in phase-II trials, which increase the insulin supply.  So those two treatments together might represent a relatively quick path to a cure, if they both pan out and work well together.

News Article: http://money.cnn.com/news/newsfeeds/articles/marketwire/0580389.htm

Transition Therapeutics Announces Results of a Phase 2 Study of TT-223 in Type 2 Diabetes Patients
  
At one time it was hoped that TT-223 would help type-1 diabetics regrow their beta cells and generate more of their own insulin.  However current testing is limited to type-2s (as in this trial).  The good news is that it worked for type-2s: the treated group A1C dropped by about 1.13, while the untreated group dropped by only 0.22.  

To me, this suggests that if we are successful at stopping the autoimmune attack, then TT-223 might be helpful in helping to regrow beta cells.  But so far, there is no evidence that TT-223 would be helpful as a single treatment for type-1 diabetics. 


Press release: http://money.cnn.com/news/newsfeeds/articles/globenewswire/182542.htm

Joshua Levy
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF news, views, policies or opinions.

Hovorka's Aritficial Pancreas Results

Hovorka's Artificial Pancreas Results

Lancet is publishing a paper on Hovorka's AP work.  This work is funded by JDRF (and several European diabetes charities), but is not part of the recently announced collaboration with Animas.

The basic trial was to take 17 kids and teenagers, and have each use a closed loop system while they slept in a hospital (with a nurse double checking that all was well).  One interesting wrinkle was that some of the patients exercised just before going to bed, others ate a large meal, while others did neither.  The idea was to test some situations which would push the AP into tougher situations.  Testing at night and in a hospital is definitely targeting the easiest time of day in the easiest environment. Commercially available pumps and CGMs were used (Smiths Medical, Abbott Diabetes Care, and Medtronic).

I thought the results were good for a phase-II type trial.  Patients using regular pumps were in range 40% of the time during the night.  But when they used the AP, they were in range 60% of the time.  Even better, the regular pumpers went very low nine times, but the APers never did.   So if you want an AP to prevent "dead in bed" situations, then the results were particularly good.

News articles: http://news.bbc.co.uk/2/hi/health/8498993.stm http://abcnews.go.com/Technology/wireStory?id=9752115  http://www.nytimes.com/2010/02/05/business/05diabetes.html
Abstract: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2809%2961998-X/fulltext
Trial Record: http://controlled-trials.com/ISRCTN18155883

Joshua Levy

All the views expressed here are those of Joshua Levy, and nothing here is official JDRF news, views, policies or opinions.

Why Fund J and J / Animas / DexCom Close Loop Trials?

Note: notes like this [d1] are footnotes to more discussion at the bottom of the posting.

Why Fund J and J / Animas / DexCom Closed Loop Trials?

About two weeks ago, JDRF made a big announcement that they were helping to fund research into a closed loop system.  Basically, they are working with Animas (insulin pump manufacturer and division of Johnson and Johnson) who work with DexCom (CGM manufacturer).  JDRF was putting in about 8 million dollars over about 3 years [d0], and was hoping for clinical trials within a year, and FDA approval of a device (although not a full Artificial Pancreas, or AP) within 4 years. 

So the first thing that popped into my head was "why bother?".  By which I meant, why should JDRF bother?  I don't have any problem with JDRF funding commercial companies [d1].  But Johnson and Johnson (especially) is a huge company which could easily fund it's own clinical trials. And it is clear to me (and many others) that closed loop systems were the next big thing in pump technology.

It so happens that last weekend I found myself talking to two guys who know more about corporate research into type-1 than I do, so I asked them this very question: Why should JDRF fund research that Animas was going to do anyway, when Johnson and Johnson had the money to do it?  Their reply was simple:

Animas would never have started the research into a closed loop trial, without the money and public support of JDRF behind it.

My initial reaction was disbelief.  I pointed out that Animas was in the pump business, and the obvious next step in pump development was a closed loop of some kind.  The first company to market a closed loop pump would have a huge advantage over all the other ones.  Of course they would do a closed loop clinical trial.  It had never occurred to me that any of the pump makers would not do a closed loop clinical trial.

But I was wrong.  As I quickly learned by searching through the FDA's clinical trial site.  In fact, Animas was not doing a closed loop trial; None of the big pump companies is currently doing a closed loop trial without JDRF's involvement. [d2]. There were two reasons why not.  The first reason was pretty simple: no pump company knows how to get a closed loop pump through the FDA approval process.  For one thing, no one's ever done it.  For another thing, a closed loop system would involve both a drug and a device.  In the world of the FDA, drugs have one set of rules (and are governed by one part of the agency) while devices have a completely different set of rules (and are governed by a completely different part of the agency) and of course the rules are not coordinated, and the two parts of the agency don't talk to each other much.  So there is a lot of uncertainty about exactly what sort of testing will be required [d3].  How long it will take, and so on.  And uncertainty can be fatal to big company research.  If J and J puts 10 million of their money into it, they will not know if it will take 3 years or 10 years to get through the regulatory process.  And that's a big difference when your stockholders want quarterly profits.

The second reason was simple: if no one does it, then no one has to do it.  This is the downside of capitalism when there are only a small number of companies.  There are only a few companies that market pumps in the US.  And they are all big and highly regulated, and they know pretty much what each other are doing.  So as long as they know that none of their (limited) competition is developing a closed loop system, they don't have to develop one [d4].

So here are some reasons why funding a closed loop clinical trial is a good thing for JDRF to do:

1. It (hopefully) gets one closed loop approved, so people can use it.
I'll put together another post on why closed loop is a good thing, even if it is not a cure.  It's too big a subject to put here, but as a quick summary: an AP is likely to lower many (if not all) of the long term complications of type-1 diabetes.  An AP is likely to be easier to use than a pump, and require much less work on the part of the diabetic.  An AP is likely to prevent the worst single complication of type-1 diabetes: "dead in bed". And an AP may well be required by the eventual cure, because excellent BG control from an AP may be required to regrow beta cells as part of an eventual cure.

2. It might motivate other big pump companies into starting their own clinical trials.
Capitalism is based on competition between companies.  So having JDRF work with one company is likely to motivate other companies to start, hurry, or continue their own research.  So putting money into Animas helps them directly, but also motivates Medtronic and Omnipod to put more of their money into similar research, or to work with JDRF themselves [d5].

3. Once one closed loop system is approved, it will be easier for the others.
One of the problems with the FDA approval process (especially for a combined drug/device), is that the first one through the gate pays a big price both in terms of extra work, but more so in terms of extra uncertainty.  So everyone wants to be second through the process.  Let someone else figure out the rules, and once they are known, then just go through.  Let someone else clear the path.  So if JDRF's money helps clear the path (ie. push Animas through the approval process first) it will end up benefiting Medtronics and Omnipod as well.  And in the end, all type-1 diabetics.

Put another way, consider this: If you have a problem, then you have a problem.  But if you can solve that problem with money, then you merely have an expense.  Companies don't like problems, but understand expenses very well.   Right now, getting FDA approval for an AP is a problem; no one knows the details of how it will be done.  However, if JDRF can spend some money and work with Animas to figure out how to solve that problem, then it will merely be an expense.  And companies know how to deal with expenses.  And an AP will be forthcoming sooner.

More Discussions

[d0] Although a lot of people focus on the money (as I do here), JDRF is bringing more to the table than just money.  They are bringing their previous research (especially previously tested algorithms), and well as a patient recruitment network, etc.

[d1] I think that the goal of JDRF should be to speed development of a cure for type-1 diabetes, and if they think the best way to do that is by funding a researcher at a University, great.  And if they think the best way is to fund a researcher at a company, great.  I don't care where the money goes; I care that it speeds development of a cure.

[d2] This surprised me, but it's true.  Using the FDA's clinical trials database:
There are three studies using Animas, but not a closed loop or feedback study.
There are four studies using Omnipod, but not a single closed loop or feedback study listed.
There are thirty one studies using Metronics, but only one testing a closed loop system and that one is a joint venture of Medtronic and JDRF: http://www.clinicaltrials.gov/ct2/show/NCT00831389
There are thirteen studies covering closed loop devices in diabetes.  One of them is the joint Medtronic/JDRF trial described above.  Of the remaining twelve, all are funded and sponsored by government agencies, hospitals, or universities.  Not one is funded by a company. 

So it is clear to me that the pump companies are not going to fund clinical trials aimed at getting a closed-loop system through the FDA approval process, unless JDRF catalyzes the process.  


[d3] There have been some drug/device combinations improved in the past. For example, drug covered stents.  However it does involve much more uncertainty than either a drug or a device alone.

[d4] This is not a matter of an evil conspiracy, more a case of no one spending money on something they don't have to.   They all think, since none of my competitors is working on a closed loop, then I'll spend my millions on something else.  If one of them does start, then I will start the year after, and still be pretty close to them.  Medical pumps are not a business where being a month (or even half a year) ahead of your competition matters that much, anyway.

[d5] And it is important to remember that JDRF is not playing favorites with companies.  They already have a similar agreement with Metronic, so this one with Animas will be their second, and it shows clearly that JDRF will partner with any company that is moving the research ahead.

This blog posting was unusual in that I asked several people to review it for me and provide suggestions and feedback.  I'd like to thank all of these reviewers.  

Joshua Levy
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF news, views, policies or opinions.