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.