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

Unfortunately, this is bad news.  But here it is:

Canakinumab and Anakinra Both Fail Phase-II Trials in Honeymooners

Canakinumab (brand name Ilaris, previously known as ACZ885) and Anakinra (brand name Kineret) are different drugs, but they have a lot in common.  Both target IL-1, which is part of the immune system.  Canakinumab is already approved in the US for the treatment of cryopyrin-associated periodic syndromes. Anakinra is already approved in the US for the treatment of rheumatoid arthritis.  Unfortunately, both failed Phase-II trials for type-1 diabetes.  Here is the quote from the abstract:

Canakinumab and anakinra were safe but were not effective as single immunomodulatory drugs in recent-onset type 1 diabetes.

A previous, smaller test of Anakinra had also failed.  

Discussion

I occasionally hear arguments that testing drugs on NOD mice is the wrong approach.  That we should not bother to do that, and just go straight to human testing.  People who make this argument are quick to point out that NOD mice are commonly cured of type-1 diabetes, but none of these cures have worked in people.  They often go a step farther and suggest that maybe NOD mice are so different that they are leading researchers astray.  That a successful mice cure means it won't work on people, and conversely that drugs that work on people might not work on mice.

However, both of these drugs were tested initially in people.  They were never tested (alone) in NOD mice.  And they both failed.  Of course, two examples don't prove anything.  However it does support the idea that curing type-1 diabetes is tough no matter if you test first in mice or first in people.

Abstracts:

http://www.lancet.com/journals/lancet/article/PIIS0140-6736%2813%2960023-9/abstract

http://www.ncbi.nlm.nih.gov/pubmed/21518168?dopt=Abstract

Clinical Trial Records:

http://clinicaltrials.gov/ct2/show/NCT00947427

http://clinicaltrials.gov/ct2/show/NCT00711503

http://clinicaltrials.gov/ct2/show/NCT00645840

Wikipedia:

http://en.wikipedia.org/wiki/Canakinumab

http://en.wikipedia.org/wiki/Anakinra

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. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog. 
Clinical Trials Blog: http://cureresearch4type1diabetes.blogspot.com
Cured in Mice Blog: http://t1dcuredinmice.blogspot.com/

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

Canakinumab Completes Enrollment
Canakinumab is a monoclonal antibody, which is designed to lower inflammation.  It targets IL-1β (interleukin-1 beta) which causes inflammation.  The drug was approved in 2009 (both US FDA and EU EMEA) for a collection of rare autoimmune based inflammatory diseases.  (And type-1 is an autoimmune disease which causes inflammation, but it is not clear how important the inflammation is to the symptoms of the disease.)  Good results have been seen in people with type-2 diabetes, and it has been used in children as young as 3.

They have completed enrollment of their phase-II clinical trial (66 people) as of March 2011. Because this drug is already FDA approved, there was not a phase-I trial in people with type-1 diabetes.  So the results from this trial will be the first type-1 results that we see.

Why is completing enrollment important? For two reasons.  First, because it is now possible to predict when they will finish collecting data.  This study runs for 2-4 years, so they should have data collected by March 2015 at the absolute latest, and might have some early data by March 2013.  Second, because much of the uncertainty that surrounds clinical trials, is involved with recruiting participants.  It is often unclear how hard it will be to recruit people, and long it will take.   But that this point, all that uncertainty is behind the researchers.  From now on, it is just gather data, then analyze data, and then publish data.  Researchers have a lot more control over those later stages, then over recruiting people in the first place.

Clinical Trial: http://www.clinicaltrials.gov/ct2/show/NCT00947427
Wikipedia entry: http://en.wikipedia.org/wiki/Canakinumab

Xoma 052 Fails (Mostly) in Phase-II for Type-2

Xoma 052 is a monoclonal antibody which is a broad anti-inflammatory, and works by blocking the IL-1 inflammation pathway.  The news is that Xoma announced that their Xoma 52 phase-II trial for type-2 diabetes had missed it's primary end point (which was better BG control).  They are still hopeful that it will lower bad cholesterol and be marketable for that purpose.  But that's a big come-down: they were hoping to lower BGs which is a big, sweeping treatment for type-2, but now they are hoping to help one particular symptom.  Plus, there are already other drugs that lower bad cholesterol.

Why is this important? Xoma is also testing this drug on type-1 diabetics.  That trial is ongoing and results are not expected until around October 2011.  But obviously, this is not good news.  However, since the mechanisms behind type-1 and type-2 are very different, we really need to wait and see what happens in their type-1 clinical trial.

Reminder About The Blog
This blog generally only covers research results.   Occasionally related topics are discussed.   However, I generally don't discuss funding issues, stock issues, new hires (such as presidents, new board of director members, etc.)  patient issues, mergers and acquisitions ("M&A"), director or C-level resignations, etc.  These are all news worthy, but they are not the kind of news that I cover 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
To Get as Email Join here: http://groups.google.com/group/type-1-diabetes-clinical-trials-news

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

Polyclonal Tregs Starts a Phase-I Clinical Trail

This one is a little complex.  The body's immune system includes T-regulatory cells, which help control the "killer" T-cells which (in type-1 diabetes) mistakenly attack the beta cells.  Some researchers have attempted to reduce the number of "killer" T-cells, while other researchers are trying to raise the number of T-regulatory cells.  This research is trying to raise the number of T-regulatory cells.  The basic technique is as follows: remove some of a patient's own T-regulatory cells, which is the same processes as giving blood.  Then separate and purify those T-reg cells, and grow them for about 2 weeks.  You can end up with 1000 times as many as you started with. Finally, put them back into the patient.  Since these cells naturally regulate (or control) the body's immune system, having more of them may result in the body stopping it's own autoimmune attack.   They've had good results in NOD mice.  Finally, some researchers believe that the previously seen good results in some other treatments (such as anti-CD3 and ATG) might be caused by these treatments stimulating T-reg production, rather than, or in addition to, lowering "killer" T-cell production.

This study involves 14 people, who have had type-1 diabetes for more than 3 months, but less than 2 years.  It is primarily a safety trial (to make sure the procedure is safe), but has secondary measures to also see if the treatment improves type-1 diabetes (for example: higher C-peptides, lower A1Cs, etc.).  It is a single site study, being done at UCSF (San Francisco, California, USA).  Dr. Gitelman  ("Dr. Steve", if you attend Bearskin Meadows camp) is running it.

Unfortunately, this study will not be quick.  It is expected to last until 2016.

Clinical trial record: http://www.clinicaltrials.gov/ct2/show/NCT01210664
UCSF's web page: http://www.diabetes.ucsf.edu/clinical-care-education/clinical-trials/type-1-diabetes/new-onset-type-1-diabetes-age-6-45-years-wit

Canakinumab Starts a Phase-II Clinical Trial

Canakinumab is a monoclonal antibody, which is designed to lower inflammation.  It was approved in 2009 (both US FDA and EU EMEA) for a collection of rare autoimmune based inflammatory diseases.  Good results have been seen in people with type-2 diabetes, and it has been used in children as young as 3. Therefore, it is known safe, and can start a phase-II trial for type-1 diabetes.  The trial is for 66 people who will be followed for 4 years.  It is honeymoon only (100 days from diagnosis).  The treatment is monthly injections for a year: 2/3 get treatment, 1/3 get placebo.  My general comments on inflammation based cures apply here: http://joshualevy.pbworks.com/w/page/24444346/ConceptsAndBackground#Inflammation

This is a large trial, recruiting in many locations in the US, which are listed in the clinical trial record below.  For locals: both UCSF and Stanford are participating.

Clinical trial record: http://www.clinicaltrials.gov/ct2/show/NCT00947427
Wikipedia entry: http://en.wikipedia.org/wiki/Canakinumab

Data Published from extended follow up to Diamyd Phase-II Trial

Diamyd as published some extended follow up up data from their phase-II trials, which I have not had time to review, but you can see it here:

Full Paper: http://www.springerlink.com/content/k7051252031r1671/fulltext.html
Clinical Trial: http://www.clinicaltrials.gov/ct2/show/NCT00435981

Not Yet In Human Trials

There were several new types of artificial pancreas which I heard about in 2010, and this is the latest.  It is called a "Bionic Pancreas" and is basically a dual-hormone (insulin and glucagon) AP, but designed as a single, custom computer chip.  They hope to start human trials "this year [2011]".  These guys know about the dual-hormone work being done at Harvard, and the two groups are using some of the same ideas, but pushing different parts of the technology.  The Harvard guys are focused more on exact algorithms, and these guys (at Imperial Collage, in the UK) are focused more on a single chip package.

News report: http://spectrum.ieee.org/biomedical/devices/bionic-pancreas

Not Type-1 Diabetes Related

The following article describes the ethical issues of a chemist who works with brain chemicals in rats, and who's work is often used by black marketeers to create street drugs, which sometimes kill people.  It is an interesting read and an interesting moral dilemma.

http://news.yahoo.com/s/ap/20110105/ap_on_sc/us_sci_haunted_scientist;_ylt=Apj8w6un3xq9J8J_t4MMSEAPLBIF;_ylu=X3oDMTJwM2I5NnNlBGFzc2V0A2FwLzIwMTEwMTA1L3VzX3NjaV9oYXVudGVkX3NjaWVudGlzdARjcG9zAzEEcG9zAzIEc2VjA3luX3RvcF9zdG9yeQRzbGsDc2NpZW50aXN0aGF1

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