Possible Cures for Type-1 in the News (late June)

Low Dose Naltrexone starts a Phase-I Trial

Background
Naltrexone was approved in 1984 for use in treating heroin addiction, but was never widely used, because of strong side effects.  The low dosage level is one tenth the dose approved, so it is much lower, and doesn't have these strong side effects. Low Dose Naltrexone (LDN) is undergoing several clinical studies aimed at different diseases.

Here is how the researchers describe this trial:

The purpose of this early study is to see if a drug called naltrexone should be studied more in people with Type I diabetes and hypoglycemia unawareness. This study will show whether naltrexone could reduce hypoglycemia unawareness. The study will also show, by using magnetic resonance imaging (also called MRI), whether naltrexone changes the way blood flows in the brain when a person is experiencing hypoglycemia.

Discussion
I'm not sure if I'm going to follow this trial as a potential cure, because it seems to be focused very specifically on "hypoglycemia unawareness", and that is not a cure.  On the other hand I mention it here, because I know that some people are very interested in Low Dose Naltrexone, and it is the first time LDN has been tried on type-1 diabetes.  Unfortunately, they are going going to be measuring blood flow in the brain, and too-low blood sugar events.  Some people think that LDN might result in lower insulin requirements, and producing more natural insulin.  However, this trial is unlikely to detect that (unless they test for more things than are mentioned in their clinical trial record). 


Clinical trial: http://www.clinicaltrials.gov/ct2/show/NCT01053078
Wikipedia: http://en.wikipedia.org/wiki/Naltrexone 
Facebook group: http://www.facebook.com/group.php?v=info&gid=342192490776 


LCT's DIABCELL: Two Year Delay to General Availability

Dr. Elliot (a major player at LCT) said in a public forum:

"We do not anticipate being in the clinic before 2013 and even then in a very limited way."   Source: http://islet.org/forum/messages/53927.htm

This is a two year delay compared to their previous statement (in a yearly report) saying that they hoped to be doing transplants in Russia by 2011.

Also, LCT made a very nice presentation at ADA, which you can see here:
http://www.asx.com.au/asxpdf/20100628/pdf/31r13z624mnx7g.pdf
The really interesting slides start on page 30 and runs to the end (although slides 22 and 27 aren't bad, either).

Artificial Pancreas Photo
Here is a link to a "puff piece" in a Boston newspaper about the "bihormonal" (glucagon and insulin) AP work:
http://www.bu.edu/today/node/11148
The reason I include it is because it starts out with a big photo of a person with this AP.  Notice the five different "sets" on the person's abdomen.  It's a good reminder of where AP is and is not. How far we have come with an AP, and have far we have yet to go.

Dr. Ward's Artificial Pancreas Trials
This newspaper article describes some AP trials being done in Oregon, USA:
http://www.earthtimes.org/articles/press/an-artificial-pancreas-closer,1359773.html

These guys are testing a bihormonal (glucagon and insulin) AP device, similar to El-Khatib's group in Boston, Massachusetts, USA.  However these guys are using a different computer algorithm to control the hardware.  The key achievements include an average BG of 138 and "nighttime hypoglycemia was reduced nearly to zero".  Testing was for a 24 hour period.  I think that 21 people were involved.  (The newspaper article says "21 experiments".)

Stem Cells
I recently came across a group of 8 stem cells experiments (mostly phase-I) which did not require long term immunosupressives.  So those could be part of a future cure.  For example, if Diamyd, DiaPep, or any of the anti-CD3 treatments currently in phase-III trials pan out in honeymoon diabetics, then these stem cells might extend that cure to people with established type-1 diabetes.  I will devote a future posting to these Stem Cells trials.  With the 3 stem cell trials that I already knew about, that's 11 total. 


Joshua Levy
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions.
Blog: http://cureresearch4type1diabetes.blogspot.com
Web: http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials

Three New Treatments Preparing to enter Phase-II or Phase-I Human Trials

This is a "hat trick" of new drugs preparing to enter phase-II trials for type-1 diabetes.  Each one of these has started the paperwork part of a clinical trial, but none of them have started recruiting patients as yet.  The first and last are similar anti-inflammatory drugs already approved for CAPS, while the middle is a immunosuppressive.

 
Canakinumab (ACZ885) Preparing for a Phase-II Trial
Canakinumab is a human monoclonal antibody targeted at interleukin-1 beta, and was approved for the treatment of cryopyrin-associated periodic syndromes (CAPS) by the US FDA and the EU EMEA in  2009. CAPS is a spectrum of autoinflammatory syndromes, and some researchers believe that inflammation is important to the type-1 diabetes process.  It is being developed by Novartis.

There is no location information in the clinical trials entry, but the responsible party is Dr. Jay S. Skyler, so I would guess Miami, Florida, USA.  The plan is to enroll 108 patients and complete in December 2014.  It is honeymooners only, you must enroll within 100 days of diagnosis.  This drug has not previously been tested on type-1 diabetes, but skips phase-I trials because it is already approved for other diseases.  It is currently in use in about 21 phase-II and phase-III clinical trials for about several different inflammation based diseases, especially Gout, Type-2 Diabetes, and Arthritis. 


clinical trial: http://www.clinicaltrials.gov/ct2/show/NCT00947427
wikipedia: http://en.wikipedia.org/wiki/Canakinumab

Alefacept Preparing for a Phase-I Trial
Alefacept is a genetically engineered immunosuppressive drug sold under the brand name Amevive was approved in 2004 for sale in Canada, the United States, Israel, Switzerland  and Australia. But not in the EU.  It is used to control inflammation  in moderate to severe psoriasis with plaque formation, where it interferes with lymphocyte activation.  Since psoriasis is an autoimmune condition broadly similar to type-1 diabetes, it is quite reasonable to try it.  However, the lack of approval in EU is worth noting; it seems to generally suppress the immune system, which can lead to side effects.  Obviously, the perfect drug would suppress the autoimmune attack on beta cells, without suppressing any other autoimmune attacks.  Usually the EU's EMEA approves new drugs (and especially new devices) more quickly than the US's FDA, but that is not the case here.


This study will be run at Emory University (Atlanta, Georgia, USA) and plans to enroll 45 patients and complete in October 2014.  It is honeymooners only, you must enroll within 6 weeks of diagnosis.  This drug has not previously been tested on type-1 diabetes, but is already approved for other diseases, as described above.  It is currently in use in about 37 phase-II, phase-III, and phase-IV clinical trials (several completed) for several diseases, especially Psoriasis.   This study is done in collaboration with Astellas Pharma US, Inc.

clinical trial: http://www.clinicaltrials.gov/ct2/show/NCT00965458
wikipedia: http://en.wikipedia.org/wiki/Alefacept

Rilonacept Preparing for a Phase-II Trial
This drug is has been available since 2008 to treat CAPS under the name Arcalyst.  It is an interleukin-1 inhibitor.

This study will be run at University of Texas Southwestern Medical Center (Dallas, Texas, USA) and plans to enroll 72 patients and complete in June 2012.  It is ultra-honeymooners only, you must enroll within 2 weeks of diagnosis.  This drug has not previously been tested on type-1 diabetes, but skips phase-I trials because it is already approved for other diseases.  It is currently in use in about 12 phase-II and phase-III clinical trials for about several different inflammation based diseases, especially Gout.


clinical trial: http://www.clinicaltrials.gov/ct2/show/NCT00962026
wikipedia: http://en.wikipedia.org/wiki/Rilonacept (but not much here)

Joshua Levy
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions.
Blog: http://cureresearch4type1diabetes.blogspot.com
Web: http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials

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

AAT (Alpha-1 Antitrypsin) Starts Phase-I 
Omni Bio announced that the Barbara Davis Center for Childhood Diabetes has received IND (Investigational New Drug) regulatory clearance from the U.S. Food and Drug Administration (FDA) to start a Phase I clinical trial evaluating Alpha-1 Antitrypsin ("AAT") in patients with type I diabetes.

This is an anti-inflammatory drug, which the body makes naturally, and which is already FDA approved for people who have a rare condition where a person don't make enough of it on their own.  You can read my general comments about all inflammation based cures: http://joshualevy.pbworks.com/ConceptsAndBackground#Inflammation

There is not yet a clinical trials record for this,  but the press release says they will start out with 15 people in a phase-I trial, and will try to expand to a 50 person phase-II study.  This is all being done at the Barbara Davis Center in Denver.  People in the trial will get the drug for 8 weeks, and then be followed for 2 years.  It is not clear if this will be honeymoon only, or established diabetics only, or both.

Press release: http://www.omnibiopharma.com/admin/files/file/OMBP%20IND%20CLEARANCE_JEFFERIES_FINAL%206%208%202010.pdf
Corporate web site: http://www.omnibiopharma.com/

Welcome a new treatment and a new company to the world of clinical trials to cure type-1!

Some Discussion
One of the questions that I often get asked about mice cures is "how long until this is available for people".   My stock answer is "for a new drug, at least 10 years from the start of human testing (clinical trials)".  That's a true answer, but not a complete answer, because they are usually asking right after the announcement of a successful mouse trial, but before any human trials have started.  So part of the answer is how long does it take to go from the end of animal trials to the start of human trials.

This research has taken almost exactly 2 years to make that transition from animal testing to human testing.  So that is one solid data point on how long it takes.  But remember, this drug is already FDA approved for another disease, so it is probably quicker at making the transition, than a previously unapproved drug.

One Year Delay on Dr. Faustman's Results 

In May 2010, Faustman's Lab updated their FDA clinical trial record to reflect these two new dates:
Estimated Primary Completion Date: December 2010  (Previously it had been December 2009)
Estimated Study Completion Date:  February 2011  (Previously it had been Feburary 2010)
No other updates were made.

So this represents a one year delay in completing their phase-I study.  The first date is the "data complete" date, when they hope to have gathered all the data needed for the study.  The second date is the date when everything associated with the study will be completed.  I think it is fair to say that the second date is the earliest possible publication date for the results, although the actual publication date is likely to be months after that.  The only good part of this news, is that we have already waited through a couple months of the delay, so we only have about a year to wait.  (I"m assuming that if the study is complete in February, it will get published later than same year.) 

This is only the latest in a long line of delays for Faustman's phase-I study.  It was originally expected to take 7 months and be completed in July 2008.  After a series of four delays, it is now expected to take about 37 months (if it meets it's December 2010 date).  In late 2007, they thought they were about 7 months away from data completion, and now, in mid 2010, they still think they are about 7 months away from completion.  (Actually, that's closer to 3 years without forward progress.)  One way to look at this, is that they have made no visible progress in completing their phase-I trial in the last 2+ years.

Personal opinion: I think that for any research study where delays have been over four times longer than the original total length of the study (7 months of original length vs. 30 months of delay), that study is in real trouble.  And especially, this study, which only involves studying 25 people for 3 months each.  At it's heart, it is a small, simple study, using an already approved drug.  What could cause it to take 5 times it's original length, and still not be complete?  In a future blog entry I hope to write about what could cause such a delay.  But as a "teaser," I don't see how it could be just one problem.  The worst single problem you might have might double the length of your trial, because you would have to restart from the beginning.  But this trial is about 5 times longer than initially expected.  Also, at least once, the delay occurred after recruiting was complete.  The only way that could happen is there was a problem with the data gathered, so it had to be gathered again, or if the problem was found during data analysis.

Animal Research
The Lee Iacocca foundation is now funding Kineta.  Later this year, Kineta hopes to start human trials on SK-186, which is a inflammation based treatment for type-1 diabetes.   Here is the rational for this drug:

ShK-186 is a potent and highly specific Kv1.3 potassium channel blocker. It is designed to suppress activation of effector memory T cells, which are important mediators of inflammation and tissue damage in MS, type 1 diabetes mellitus and other autoimmune diseases. The drug candidate has been shown to significantly reverse disease in animal models of MS and rheumatoid arthritis. Animal models also have demonstrated that efficacy is achieved without the generalized immunosuppression that occurs with competing therapies.

You'll notice that they don't report any success for type-1 diabetes in animal models.  As above, remember my general comments about all inflammation based cures: http://joshualevy.pbworks.com/ConceptsAndBackground#Inflammation


There are currently four other inflammation based cures in clinical trials (including AAT, above).  Even a few years ago, there were none at all, so this is a growth area of research.


Press release: http://www.kinetabio.com/press_releases/PressRelease03292010.pdf
Corporate web site: http://www.kinetabio.com/
 

Request for Help
I'm trying to track down information on a clinical trial of NI-0401 by NovImmune, a Swiss company.  The company is very specific that a phase-I trial has started in the Netherlands, and I've seen other references to the trial as well.  But I can not find any official record of it.  No clinical trial record, and no registered trials record, either.  Does anyone know anything about this trial?  NI-0401 is supposed to be an anti-CD3 humanized monoclonal, so much like Otelixizumab and Teplizumab.

Joshua Levy
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions. 
Blog: http://cureresearch4type1diabetes.blogspot.com
Web: http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials

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

I didn't quite get this out by the end of May, but it is the May update.....


Andromedia Starts DIA-AID2: Second phase-III Trial of DiaPep 277
Andromedia just (in April 2010) started their second phase-III trial, which will enroll 450 people and is planned to last until March 2014.  Both the EU and the US require two large scale trials for approval of new drugs, so if this study and their earlier DIA-AID trial both work well, then the approval process can start mid-2014.  It usually takes a year or two for marketing approval, so 2015 or 2016.  This treatment has only been tested on honeymoon diabetics.  

Neither this treatment nor ToleRx's (described below) will cure people by themselves.  They are both attempts to preserve some beta cells and so either extend the honeymoon or make the continuing diabetes "less brittle" in terms of fewer quick BG drops.  In both cases, I need to put together a blog posting on exactly how effective they were in their phase-II and early phase-III results.

Andromedia's DIA-AID2 page: http://www.andromedabio.com/clinical_trials.php
Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT01103284


ToleRx Starts DEFEND-2: Second phase-III trial of Otelixizumab
This must be the month for starting second (sometimes called "confirmatory") phase-III trials, since ToleRx is also starting one of these.  The news is just as good as Andromedia.  Actually better, since ToleRx hopes to finish their second phase-III by May 2013.  The study will have 396 people.  The same market approval math works here, so 2014 or 2015, but only if they finish their second phase-III as expected, and with the results they expect.  Both of their phase-III trials are limited to honeymooners only (so any approval would only be for newly diagnosed).  Their phase-II clinical trial (called "TTEDD") did enroll non-honeymooners.  However, it looks like good results were only seen for honeymooners (but I don't have the details handy).  That would explain why their phase-III trials are all honeymooners only.


TolerRx's DEFEND-2 page: http://www.clinicaltrials.gov/ct2/show/NCT01123083
Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT01123083
 

Data from XOMA Phase-I on Behcet's Disease
Previous blogging on XOMA 052: http://cureresearch4type1diabetes.blogspot.com/search/label/Xoma
Current Status on XOMA 052: http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials#Xoma052byXoma

Behcet's Disease is an auto-inflammatory condition, which is rare in the US, but more common in Turkey.  Since XOMA 052 is an anti inflammatory, it is a natural drug to test on the disease.  It's of interest to people with type-1 diabetes because XOMA 052 is also being tested for both type-1 and type-2 diabetes (in separate phase-II trials).  Link to why inflammation might be a cause of diabetes:
http://joshualevy.pbworks.com/ConceptsAndBackground#Inflammation
(but remember that this is a minority opinion).

So, with all that a background, their results are very good (but on a very small group of people).  This trial only included 4 people.  However each person involved showed real improvement to their Behect's symptoms.

My take on this research is as follows: It shows that XOMA 052 has a major impact on inflammation in a situation similar to (but not identical with) type-1 diabetes.  So, if inflammation is a causative factor, or if reducing inflammation allows the pancreas to regrow, then XOMA 052 has a good chance of being successful.

Also, there is news about Xoma's phase-II trial in type-1 diabetics.  They have changed it considerably from the last time I looked.  It is a 24 person study, which started in Feb 2009 and is expected to finish in July 2011.  Since it lasts a year, if they finish enrollment in July 2010, then they will be on track to finish the study a year later.  This trial is open to non-honeymoon diabetics only, but there is only one site: Zurich, Switzerland.

So there are now at least two phase-II trials aimed a curing diabetes via anti-inflammatories, and they will both have results in 2011, so that might be a pivotal year for the whole idea of cures based on anti-inflammatories.

News: http://www.marketwatch.com/story/abstract-published-on-initial-results-from-xoma-052-clinical-trial-in-behcets-disease-2010-05-12?reflink=MW_news_stmp
Abstract: https://b-com.mci-group.com/Abstract/Statistics/AbstractStatisticsViewPage.aspx?AbstractID=19942&ItemsPerPage=20&AppliedFilter=[SubmitterFullName]%20Like%20%27Ahmet%20%%27&ShowOnlyInFinalAcceptance=true


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

El-Khatib's Group Announces Phase-I Results

If you are following Artificial Pancreas (AP) research, this announcement has it all: good experimental design, good results, a bright future, and some interesting side discussions.

First, the study:  These guys are testing an artificial pancreas which uses both Lispro insulin and glucagon.  Other AP projects are only dosing insulin.  Obviously, this gives the AP more control, it can dose insulin for highs and glucagon for lows.  The study was 11 patients none of whom generated their own insulin (so honeymooners excluded).  The study ran 27 hours and included 3 meals.

Second, the results: the 11 patients fell into two groups as far a results go, as described in the abstract:

In six subjects, the closed-loop system achieved a mean BG concentration of 140 mg/dl, ... There were no instances of treatment-requiring hypoglycemia. Five other subjects exhibited hypoglycemia that required treatment; 

So basically in the initial trial, it worked completely for six patients, but only partially for the other five.  So then they "tuned" their software, and got these results:

prevented hypoglycemia in both groups while achieving an aggregate mean BG concentration of 164 mg/dl.

So after tuning there were no more problems with lows, but the average BG was 164.
Now, remember that the current ADA guidelines for BG control is 154.  So the 140 is just within range, but the 164 is just out of range.  (Assuming you have a really accurate BG meter, of course. :-)  So for a phase-I trial this is a great result.

But the actual news is even a little better than averaging 164, because the researchers were able to discover why half the people did so much better than the other half in the first set of results.  The people who did well absorbed lispro insulin in about an hour, while the group that had low BGs absorbed it in about two hours.   One of the things that these researchers found, was that insulin is absorbed at different rates at different times, even by the same person.  So it is not a question that some people absorb it quickly or slowly, it's also that even in the same person, sometimes it will be absorbed quickly and sometimes slowly.  To quote Dr. El-Khatib (per. comm.):

We saw variations in the rate of insulin absorption by as much as 40–50% in some subjects between their first and second visits, as well as in an additional screening test that we ran on each subject.

(Think about this the next time you are wondering why the same dose of insulin has a different effect the next time you use it.)

I saw only three issues in this trial which made me nervous about it's applicability, and two are going to be addressed in research these guys hope to start very soon.  The first issue is activity.  For this test, the patients were lying in bed or sitting in a chair, so that was not realistic.  Second, they were using blood measurements of BG levels, not standard CGM measurements.  Third is the regular use of glucagon.  I discuss these issues below.

Third, the future:  For the one day the experiment was run, for 6 out of 11 people, the algorithm worked.  If these phase-I results carry forward into phase-II, phase-III and general availability, then this algorithm is likely good enough for a commercial AP.  Obviously, I would expect improvements so that phase-II and III would have even better results than these.  But these results by themselves are very good.

This research group is already planning to run follow on trials in Boston.  This first trial was run with very limited activity. But a follow on clinical trial will last longer (two days instead of one), use CGM technology, and more accurately represent real activity.  Patients will be able to move around (although they will be pushing around a pole with equipment on it), and they will spend some time on treadmills to model exercise. After that, there is a third trial, a follow on to the two day test.  In that third trial, people will use the bihormonal AP for a total of 5 days while "out and about" (doing what they would normally do).

Another difference in the future trials will be a partial pre-meal bolus.  This will be based on weight, and given with meals.  The researchers expect that this will keep them below the ADA's BG guidelines, especially patients who absorb insulin more slowly.  So if you know the JDRF "stages" of AP development, this would be a stage 6 AP because it includes glucagon, but a stage 4 AP in that you need to tell it when you are having a meal.  In either case, a big improvement over nothing, which is the kind of AP we (in the US) have now, or stage 1, which is available in parts of Europe.  You can read more about JDRF's stages here:
http://cureresearch4type1diabetes.blogspot.com/2009/09/background-for-artifical-pancreas.html

The use of standard CGM technology, starting in the next trial, is another important step forward, in my opinion.  CGM technology has some real limitations, and one of the big open questions in AP development is this: is current CGM technology good enough to feed a successful AP?  The completed trial doesn't directly address this, because they were using BG measurements from the blood stream, not interstitial spaces where CGMs work.

This work is based on giving Lispro for highs and glucagon for lows.  We have a lot of experience giving people insulin when their BGs are high, but much more limited experience giving people glucagon for lows.  Sure, we all have needles in red boxes, and some have even experimented with "microdoses" of glucagon.  But still, this AP will use glucagon much more than has been done in the past, and that is something that must be tested.

For the software nerds out there: basically, the software to control the pumps has one basic algorithm.  It's this basic algorithm that they are testing, and they are not going to change that. However this algorithm has a couple of parameters which the researchers can change.  Two of these involve how quickly insulin is absorbed, and these are the two that they changed in order to "tune" the algorithm for people who absorbed insulin more slowly.

Finally, a little fantasy of mine:  For one of the big diabetes meetings in 2011 or 2012 (ADA, or EASD, or "Friends For Life") there will be enough successful AP research projects, so the can have a "bake off" right there at the convention.  Each team brings a couple of APs, and some convention goers use them for the duration of the convention.  Then in the last session, they become a panel that discusses the current state of APs from a patient point of view.  Someone can chart their BGs on a couple of slides to get the discussion rolling.   I'd love to get a clinical trial number for that......

Research web site: http://www.artificialpancreas.org/
Abstract: http://stm.sciencemag.org/content/2/27/27ra27.abstract
Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT00811317
Full paper: http://stm.sciencemag.org/content/2/27/27ra27.full.pdf?keytype=ref&siteid=scitransmed&ijkey=LwlywxnAol4yc
Extra data: http://www.artificialpancreas.org/uploads/ElKhatib_and_Russell__et_al_SOM_Sci_Trans_Med_2010.pdf

How to Summarize AP Clinical Trial Status

I'm also thinking about how I can summarize an AP clinical trial is just a few lines, that are understandable.  For this trial, I'm thinking about something like this:

A phase-I trial of 11 people over a 1+ day time period which includes meals but not activity.
Results: The algorithm had 6 people averaging BG of 140 and no lows.  After tuning, all 11 averaged BG of 164, and no lows.
Notes: This AP could dose both insulin and glucagon.  Commercial CGMs were not used (blood BGs were).

If anyone has any thoughts on how to summarize AP clinical trials, please do share them with me. 

I would like to thank Dr. Steven Russell (a principal investigator in this research) for answering my questions, and also Dr. Firas El-Khatib (a Co-investigator in this research) for providing additional information.  All mistakes are my own.

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

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.