Levicure's Combination Therapy

Levicure is a startup which is currently raising money to fund a phase-II trial for a combination therapy designed to prevent or delay T1D if given during the honeymoon period.  This blog posting is reporting on the results of their retrospective phase-I clinical trial.  That trial has already been completed and is motivating them to move forward with a larger phase-II trial. 

The combination therapy used three medicines: GABA, Sitagliptin or Saxagliptin (which are dipeptidyl peptidase-4 inhibitors), and Omeprazole (a proton pump inhibitor).  All three of these drugs are available now, and all have some evidence that they will help people with diabetes.  They have all been tested (in some cases in combination with other medicines and each other).  However, I think this is the first clinical trial that has reported on these three together.

The Study

This was a retrospective study, where the researchers reviewed the medical records of people who had been treated with the three drugs.  The people were given the three drugs because their doctors thought it was the right treatment for them, not because they were enrolled in a trial.  There is no randomization process and no control group.  The trial size is determined by how many people got all three treatments in the time period the researchers looked at.

The researchers ended up with 19 people. Ten of them had received the three drugs during the first year after diagnosis (their honeymoon period).  Nine more had received the drugs after that, so they had established T1D.  The two groups were analyzed separately.

Results

The group (ten people) that started therapy during their honeymoon phase, called "early therapy" below had a statistically significant rise in C-Peptide production.  The average went from just over 200 pmol/L to just under 500.  Since the average for a person without T1D is at least 365, this is an important difference, as the change is from an abnormal result to a normal one.  (All of these are fasting numbers.) 

The group (nine people) that started the treatment more than a year after the onset of T1D did not show an improvement in their C-Peptide number, and none of them was able to stop injecting insulin.  They did show improvements in treating T1D (using less insulin, having better A1c numbers, etc.)

Company: https://www.levicure.com/
History: https://healthtransformer.co/levicure-is-developing-a-breakthrough-triple-therapy-for-type-1-diabetes-b6c521e6b2c5
Clinical Trial Report: https://www.frontiersin.org/articles/10.3389/fendo.2023.1171886/full
Animal Testing: https://www.frontiersin.org/articles/10.3389/fendo.2022.1028114/full

Discussion

LADA vs. Classic T1D

Discussion of this study needs to start out with the question: Is it a LADA study, or is it a classic T1D study, and are they different?  

The successful (early treatment) part of this study enrolled people between the ages of 17 and 58 (average age was 31 and standard deviation was 13 years), so about half of these people had LADA rather than classic type 1 diabetes.  LADA stands for Latent Autoimmune Diabetes in Adults; you can think of it as classic T1D, but diagnosed in adults.  A common cut off is 30 years old.  People under that age are said to have classic T1D and after that age, LADA.  LADA has a honeymoon, just as T1D does, but it is not the same.  It is well known to be longer and stronger.  This makes it easier for drugs that delay/extend the honeymoon to work better on LADA than on T1D.  Therefore, we don't know if the good results seen here for many people with LADA are going to be as good in people with classic T1D.

Prospective vs. Retrospective Studies

I usually report on prospective studies, which are inherently more reliable than retrospective studies, and this study was retrospective.  In this case, these researchers are already raising money for another study and that new study will be prospective, so it will provide a better signal as to the success of the treatment.  In the meantime, there is nothing to do but wait, and hope they can raise the money quickly.

Similar Studies With Semaglutide

The obvious clinical trial to compare this to is the Semaglutide study which I blogged on here:
https://cureresearch4type1diabetes.blogspot.com/2023/09/strong-results-from-pilot-study-of.html
That study was in many ways very similar, both in study design and result.  They were both retrospective studies based on clinical practice, and they both had many people off insulin for a year in the honeymoon phase.

Interestingly, Semaglutide has a similar mechanism of effect to Sitagliptin or Saxagliptin.  They all end up impacting glucagon-like peptide-1 (GLP-1).  However, Semaglutide is an injected drug while Sitagliptin and Saxagliptin (tested here) are pills. 

Availability Now

The three drugs tested here are all commonly available.  GABA is a dietary supplement, Omeprazole is sold both over the counter and by prescription.  Only the second component: Sitagliptin or Saxagliptin is a prescription drug and both have been approved for use since the late 2000s.  They each have a generally good safety profile.  If you want to have an "off label" discussion with your doctor, the exact dosing information is in the clinical trial report (link above).

 

Joshua Levy

http://cureresearch4type1diabetes.blogspot.com

publicjoshualevy at gmail dot com

All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions. My kid has type-1 diabetes and participates in clinical trials, which might be discussed here. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog.

 

Three Unsuccessful Trials

This blog posting summarizes several clinical trials aimed at curing type-1 diabetes which have failed.  These are never fun, happy blog postings, but they are important.  One of the big problems with trying to understand research based on mass media reporting is that failures are rarely covered at all.  The soundtrack for this posting is "Down" by Melissa Lambert:
http://grooveshark.com/#!/s/Down/4BHhwn

Sitagliptin and Lansoprazole Unsuccessful in Phase-II Trial

This was a combination therapy.  The researchers were attempting to combine a drug to stop the autoimmune attack and another drug to trigger beta cell growth.  Both drugs were approved for other purposes, and commonly used.  Unfortunately, it didn't work.  Summary from abstract:

At 12 months, the mean change in C-peptide area under curve was −229 pmol/L for the treatment group and −253 pmol/L for the placebo group; this difference was not significant (p=0·77).

Abstract: http://www.sciencedirect.com/science/article/pii/S2213858714701159
Blog at start of trial: http://cureresearch4type1diabetes.blogspot.com/2010/08/possible-cures-for-type-1-in-news-mid.html

Pioglitazone Unsuccessful in Phase-I Trial

Pioglitazone has been approved for use in type-2 diabetes for over 10 years. It is part of a larger drug family called thiazolidinediones which have been shown to preserve beta cells in animals with type-1 diabetes, and to reduce death of beta cells in petri dishes.  It was being tested as a honeymoon cure, but did not pan out:

Conclusion: In this pilot study, pioglitazone did not preserve β cell function when compared to placebo.

Article: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3890222/
Previous blogging: http://cureresearch4type1diabetes.blogspot.com/search/label/Pioglitazone

Stop Covering Lisofylline

As far as I can tell, no one has done human trials of this treatment for over two years, so I'm going to stop considering it as a possible cure, unless something new comes to light.  Lisofylline is an anti-inflammatory.

Previous coverage (one blog posting) is here:
http://cureresearch4type1diabetes.blogspot.com/search/label/Lisofylline


Joshua Levy
http://cureresearch4type1diabetes.blogspot.com 
publicjoshualevy at gmail dot com
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF, JDCA, or Tidepool news, views, policies or opinions. My daughter has type-1 diabetes and participates in clinical trials, which might be discussed here. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog.

Possible Cures for Type-1 in the News (early Aug-2012)

Prologue: Why Completing Enrollment is an Important Milestone for Clinical Trials

For two reasons.  First, because at that point it is possible to predict when the researchers will eventually finish collecting data.  The experimental design will say how long data will be collected for each person, so you can just add that duration to the date they finished enrollment, and that tells you when the final data will be collected.  Second, because much of the uncertainty that surrounds clinical trials involves recruiting participants, it is often unclear how hard it will be to get people, and long it will take.   But at this point, all that cunertainty is behind the researchers.  Once enrollment is complete, it is just gathering data, then analyzing data, and then publishing the data.  Researchers have a lot more control over those later stages, than over recruiting people in the first place.

Put another way, a clinical trial is made up of five tasks:
1. Do research to figure out what clinical trial should be done.  During this phase, the researchers are at the mercy of the science.  If they science doesn't pan out, then the experiment never gets done.
2. Get FDA approval for the clinical trial.  During this phase, the researchers are at the mercy of the FDA (or similar regulatory agency).  If they don't get approval, the experiment never gets done.
3. Recruiting patients.  During this phase, the researchers are at the mercy of the patients (or their parents).  If they can't get enough people to enroll, the experiment fails.
4.  Gathering the data.  During this phase, the researchers pretty much control their own destiny, unless a huge number of people drop out, or there is some unexpected safety issue.
5. Writing and publishing the results.  During this phase, the researchers are subject to editors and peer review (to some degree).  However, there are so many journals and web sites, that the researchers have many choices; they can even self publish, if all else fails.  They are not at the mercy of any one person or committee.

Completing enrollment is the end of phase 3 / start of phase 4, and you can see that researchers have a lot more control of their own destiny in phases 4 and 5, then in 1, 2, or 3.  

"REPAIR-T1D" (Lansoprazole and Sitagliptin) phase-II Study Completes Enrollment

This study finished enrolling in May 2012 and they plan to gather data for two years, so we should have results soon after May 2014.  This trail gives two currently approved drugs (Januvia and Prevacid) to type-1 diabetics within six months of diagnosis.  The hope is that it will restore or at least preserve beta cell function.

Press Release: http://www.newswise.com/articles/the-sanford-project-reaches-milestone-in-quest-to-cure-type-1-diabetes
Clinical trial record: http://www.clinicaltrials.gov/ct2/show/NCT01155284

GCSF/Neulasta phase-II Study Completes Enrollment

Previous blogging here: http://cureresearch4type1diabetes.blogspot.com/search/label/Haller

This study finished enrolling in March 2012, and they plan to gather data for two years, so we should have results soon after March 2014.  (Their clinical trial record says December 2014.) GCSF, also known as Neulasta or Pegfilgrastim, causes the body to generate it's own stem cells from bone marrow. These might rebalence the immune system or they might retrain it, but in any case, the hope is they will help cure type-1.

Burt's trial (the most successful so far) uses GCSF, ATG, and CZ. CZ is, by far, the most toxic of the three, so this trial can be viewed as "Burt ultra-lite". GCSF and ATG together would be "Burt lite" and there is a trial for that also ongoing.
Clinical Trial Record:   http://www.clinicaltrials.gov/ct2/show/NCT00662519

Thymoglobulin (ATG) Phase-II Study Completes Enrollment

Please read about Thymoglobulin (ATG) here: http://cureresearch4type1diabetes.blogspot.com/p/drugs-and-treatments-in-clinical-trials.html (scroll down the page until you see the section on ATG)

This phase-II study of ATG has completed enrollment.   It took them about 2 years longer than expected, so that's not good, but we can expect data collection to be complete in 2 years, and hopefully results will be published soon there after.  The ATG link about has complete information on why the researchers hope ATG might cure type-1 diabetes or be part of a cure.

Clinical Trial Record:  http://www.clinicaltrials.gov/ct2/show/NCT00515099
Previous blogging here: http://cureresearch4type1diabetes.blogspot.com/search/label/Gitelman

Combo (Diamyd, Lansoprazole and Sitagliptin) Trial Fails

This trial has a long and not so good history, which you can read in my previous blogging here: http://cureresearch4type1diabetes.blogspot.com/search/label/Combo

This Phase II study combined regenerative agents (lansoprazole and sitagliptin) and also 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.

This study's clinical trial record updated to show that it was terminated on 20 March 2012, although I think it had actually ended earlier.  Dr. Harlan, who started this study, had left the NIH, and the phase-III studies of Diamyd alone had failed or been canceled, so they decided not to pursue it.  

Obviously, it's too bad that it was canceled.  This was the first study that I knew of that attempted to combine a drug to stop the autoimmune attack and drugs to encourage the regrowth of beta cells.      I think that combining treatments like that is still a good thing to try, even if this specific combination did not work out.

Clinical Trial Record:  http://www.clinicaltrials.gov/ct2/show/NCT00837759

More Stable Glucagon

This is only vaguely related to a cure, but I thought I'd mention it.  Xeris is trying to create a form of glucagon which can be stored at room temperature for long periods of time.  From a cure point of view this is useful for an artificial pancreas (if you consider that a cure).  Simple APs are based on insulin alone.  However, there are more complex APs, which are based on insulin and glucagon.  Having a glucagon which was approved to sit in the pump for days, maybe weeks, would be important to these "bihormonal" APs.

As a nice side effect, it would mean that emergency glucagon needles could be preloaded, just like insulin pens, which would make them much easier to actually use in an emergency.  It also would make mini-glucagon doses much easier to administer, for those who use them.

You can think of an insulin only AP sort of like a car with a break but no accelerator.  The engine "revs high" and you run along.  You use the break to slow up.  A bihormonal AP (insulin and glucagon) is more like a car with a break and an accelerator.  More control.  The analogy is not perfect, but that's the basic idea.

Press Release: http://www.marketwatch.com/story/xeris-pharmaceuticals-awarded-phase-i-ii-nih-sbir-fast-track-grant-to-advance-stable-non-aqueous-glucagon-for-bi-hormonal-artificial-pancreas-2012-07-31

Why Pharma/Med Device Co's Apply for Approval in Europe FIRST

If you haven't read this blog posting by Scott Strumello, you should!  It compares the approval process for medical devices in the EU to the same process in the US:
http://blog.sstrumello.com/2012/08/why-pharmamed-device-cos-apply-for.html

Next Up: Results from Dr. Faustman's Phase-I BCG Trial

She published in PLoS last week, so I hope to blog about it in a week or two.

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.
Clinical Trials Blog: http://cureresearch4type1diabetes.blogspot.com
Cured in Mice Blog: http://t1dcuredinmice.blogspot.com/

Three Months of New Studies

I decided to take a look at all the studies which were reported for the first time in the FDA's Clinical Trials site between January 1st and April 1st of this year.  Registration at this site is required for all studies done on people in the US, or that will be submitted for eventual FDA drug approval, and here I"m looking at all the new ones (not updates to existing ones) for a 3 month time period.  Here is a quick summary:

51 type-1 diabetes studies started, of which:
  2 Were testing new (non-insulin) treatments for type-1
  5 Artificial Pancreas studies
  2 Studies aimed at curing/delaying type-1 during the honeymoon phase.
(none were aimed a curing established type-1 diabetes)

Obviously, I'm going to discuss these nine, and especially the last two more below, but first, I want to give a very quick summary of the other 42 studies.  The largest group (14) were testing different types of insulin (Aspart 30 or 70, Degludec, Levemir, and so on). About 5 studies were aimed at complications, about 5 had psychological targets, 2 involved new ways of giving insulin, and 2 were new BG measuring techniques, 3 involved food or diet, and so on.

If I had to select the silliest study that started in the first quarter of 2012, it would be this one: "The Effect of Guided Imagery in Children With Type 1 Diabetes Mellitus on Glucose Levels and on Glycemic Control" (NCT01567254). Unfortunately, the clinical trial record doesn't say who is funding it.

New Clinical Trial of Proinsulin Peptide on Honeymooners

Proinsulin is made by beta cells, and it is later broken down into insulin and C-peptide.  These researchers hope that giving proinsulin to type-1 diabetics in their honeymoon phase will teach the immune system not to attack itself.  This is similar to how repeated injections of peanut antigens are used over time to stop allergic reactions to peanuts.  (Note that while this trial is on honeymooners, the peanut trick works on people who have been allergic to peanuts for a long time, so it is not clear to me that this general approach is limited to honeymooners.)

There have been several clinical trials aimed at giving insulin or closely related molecules to people at risk of diabetes or in the honeymoon phase to try to train the immune system not to attack the body's own beta cells.  So far, these have not cured or prevented, but a few "rays of hope" have been seen.   So the work is continuing as researchers refine their techniques and try variants that were not tried before.  This type of treatment would likely need to be combined with a beta cell regeneration technique to result in a cure for established type-1s, and maybe for honeymooners as well.

This study will run for 3 years, and will enroll 24 people.   Two groups of eight will get proinsulin at different doses, and one group of 8 will be the placebo group.  This is double blind, placebo controlled.

This trial is being done at Cardiff, Newcastle, and London in the UK, and is part of the research done by the Diabetes Vaccine Development Centre.

Clinical Trial Record:  http://www.clinicaltrials.gov/ct2/show/NCT01536431
Patient information: http://medicine.cf.ac.uk/media/filer/2011/11/08/monopep_uhw_participant_information_sheet.pdf
Wikipedia: http://en.wikipedia.org/wiki/Proinsulin

New Clinical Trial of GABA on Honeymooners

GABA is sold as dietary supplement in the US, but this is the first trial I know of to test for type-1 diabetes in people.  It is being done by Dr. Lunsford at the University of Alabama at Birmingham.  They will measure C-peptides, A1Cs and change in insulin use over a 1 year period.  This study is double blind and placebo controled: A total of 30 people will be enrolled, 20 will get GABA and 10 will get the placebo.  To enroll,  patients must be within 12 weeks of diagnosis, although they haven't started to enroll quite yet.  The paper was filed in March, and said they planned to start in April.

Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT01561508
Wikipedia: http://en.wikipedia.org/wiki/GABA

Some Discussion of GABA

One obvious question is, why does GABA work?  I'm not exactly sure.  GABA has been studied in relation to type-1 diabetes since at least 1990.  Some work suggests that it is a immunmodulator, so lowers the immune systems attack on the body's beta cells.  Other work suggests that it lowers inflammation, so if inflammation is a trigger of type-1 diabetes, then that is a mechanism for GABA be effective.  GABA and GAD are interrelated chemicals in the body, and GAD is the most common target of autoantibodies in type-1 diabetes, so there might be a mechanism there, as well.

This research provides a strong counter example to the idea that "generic drugs can't get funding for research" or "no one will work with cheap, available drugs, because there is no profit in it" or similar canards.  GABA is widely available "over the counter" (no prescription) right now.  It is not covered by a patient, and there are dozens of companies that sell it.  Yet these researchers are able to fund and run a clinical trial for it.   GABA was reported to have cured type-1 diabetes in mice in June 2011, so it looks like it will move from mice to people in a year, which is quick.  Most treatments take about 2 years to make that transition: http://t1dcuredinmice.blogspot.com/2011/06/gaba-by-prudhomme-at-st-michaels.html

Artificial Pancreas Studies Starting in Q1 of 2012

I'm still trying to find a good way organize these, since there are so many.  My current thinking is to divide them by "stage"  (based on the JDRF's six stages of AP development), and then further divide them into commercial development and academic research, and then (finally) list them by research group.  So that is how they are described below.
Background blog posting: http://cureresearch4type1diabetes.blogspot.com/2009/09/background-for-artifical-pancreas.html

Important note: I've tended to name the research groups after one researcher involved, but I'm not sure that is a good way to do it.  I'm sorry if these groups are named after the wrong person, and I know they are all partnerships, with many people working together, I just don't have a better way to name them right now.  The names below are not designed to slight the many other researchers involved in each project!

All of these studies are recruiting new participants.

Hovorka's Group in Cambridge, UK.  Stage 3 or 5. Academic Research
12 people total, runs from May 2012 to December 2012.  Open label (non-blind, no placebo).
This study is looking specifically at children 2-6 years old, and using deluded insulin to better support them, over a 2 day period.
Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT01557634

Group in Montreal, Canada.  Stage 4 / Stage 6.  Academic Research.
12 people total, starts in January 2012.  Open label, cross over design.
This study is using a dual-hormone AP and is comparing how well it works when the pump is told about means vs. when it needs to handle meals without being forewarned of them.
Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT01519102

Hovorka's Group in the UK.  Stage 3 or 5. Academic Research
20 people total, runs from August 2011 to August 2014.  Open Label.
This looks like a long term trial of an AP, lasting 18 months, rather than the 1-3 days as is common in other studies.
Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT01534013

Montpellier University Hospital, Montpellier, France
10 people total, runs from Feburary 2012 to March 2014. Open label.This study is testing insulin delivery which is Intraperitoneal (injected into the body) rather than just under the skin, which is normal, or into a vein, which has also been done.
Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT01555788

Dr Ward's group in Oregon, USA.  Stage 6 Academic Research
10 people total, runs from March 2012 to September 2012.  Open label.
Inpatient testing of dual hormone AP.  In previoius studies, these researchers used the same hardware but entered data by hand.  In this test, they are using a truly closed loop, without human intervention.
Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT01552603


New Treatments for Type-1

One of the studies was testing Sitagliptin as an additional (to insulin) therapy for type-1 diabetes.
This is a 30 person study which is recruiting now and is expected to finish in March 2015.  It is single blind, and is testing 3 different doses of the drug, and one placebo group.  This study is being done at the Albert Einstein College of Medicine in the Bronx, New York City, USA.
Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT01530178

The other was testing Liraglutide to see if it changes the glucagon response during low BG episodes.  (I'm not sure why this is important.)  This is a 42 person study which is recruiting now and is expected to finish in September 2012.  It is double blind, placebo controlled.  Three different groups which each get a different dose of Liraglutide for some time, and then placebo for some time.  This study is being done by Novo Nordisk in Graz, Austria.
Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT01536665
Portal to all Novo Nordisk clinical trials: http://novonordisk-trials.com/website/content/worldmap-new.aspx


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.
Clinical Trials Blog: http://cureresearch4type1diabetes.blogspot.com
Cured in Mice Blog: http://t1dcuredinmice.blogspot.com/

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

Exsulin's Phase-II Trial is Data Complete 

The exact update I got on the Exsulin phase-II trial is this: "We have finished recruitment for this trial. We are still in the process of finalizing the results".  I interpret this to mean, not only have the finished recruting all their patients, but they have all their data, and are now working on the data analysis / paper writing part of the research.  This is great news, because I'm hopeful that we will hear the results in a few months.

Rituximab Starts another Phase-II Trial

Rituximab targets the CD20 part of the immune system's B cells (different from the pancreas's beta cells) to try to prevent the autoimmune attack. B cells are part of the body's immune system and communicate with the T cells, which actually attack the body's beta cells in the pancreas. By targeting the B cells, it is hoped this treatment will stop or lower the attack of the T cells.

Comment: Most treatments aimed at stopping the autoimmune attack are very focused on stopping the "bad" T cells which directly attack the beta cells in the pancreas. This treatment (if successful) opens up a whole 'nother way to stop the attack: by targeting the immune systems communication and support system, the B cells.

The current research (which I consider phase-II, although the researchers list it as phase-IV) is very similar to the a previous trial which I blogged on before (link below).  The current trial has already started enrolling 50 people at First Affiliated Hospital, Nanjing Medical University (Nanjing, Jiangsu, China). If you are interested in enrolling, contact Tao Yang, PhD at phone 86-25-83718836 ext 6466 or email yangt@njmu.edu.cn.  There is no placebo group in this trial: everyone is treated.  They started in July 2010, and hope to complete it by December 2013.  This is for people with type-1 diabetes for less than one year.

clinical trial record: http://www.clinicaltrials.gov/ct2/show/NCT01280682

A Sad Note to the Previous CD20 Research
The previous Rituximab research was led by Dr. Mark Pescovitz who died in a car crash at the end of last year.  That work was published by the prestigious New England Journal of Medicine, and was just one part of a distinguished research career.
http://www.boingboing.net/2010/12/13/mark-pescovitz-1955-.html
http://www.jdrf.org/index.cfm?page_id=114825

My previous blogging on Rituximab is here: http://cureresearch4type1diabetes.blogspot.com/search/label/Rituximab

Sitagliptin Completes Enrollment on a Phase-II Trail (as a Treatment)

This is a large (140 person) trial which started in late 2010 and is the follow on to a trial which I've blogged about before.  The goal of this is to lower A1Cs for type-1 diabetics by about 0.3, by lowering BG levels more quickly after a mean than is done now.  The 0.3 number is pretty close to what they did in an earlier, smaller trial. Sitagliptin is already approved for type-2 diabetes.  It's trade name is Januvia.

They completed enrollment in February 2011, I think.  The record is not 100% clear, and it might have been earlier.  If they did complete enrollment in February, then they will finish collecting data about June.  The clinical record says the trial will complete in July 2011, so I think it is reasonable to see results by the end of this year for this research.  This same group published their previous results very quickly after the study was done.

Clinical trial: http://www.clinicaltrials.gov/ct2/show/NCT01227460
Previous trial: http://www.clinicaltrials.gov/ct2/show/NCT00978796
Results from related trial: http://cureresearch4type1diabetes.blogspot.com/2011/02/possible-cures-for-type-1-in-news-late.html (but this was combining this drug with another)

Extra Reading

Dr. Skyler has written a wonderful summary of some of the more interesting clinical trials in type-1 diabetes done between June 2009 and July 2010:
http://onlinelibrary.wiley.com/doi/10.1111/j.1742-1241.2010.02580.x/full
One of the things I particularly liked about this paper, is that for each clinical trial, there is a summary of the abstract and then Dr. Skyler's comments.  These comments often put the research into context, discuss next steps, or give his opinions on it.  That perspective is missing from the raw scientific papers.  (Although he wrote this before the two anti-CD3 treatments had failed in phase-III trials, so those are discussed here, although they are already dead as cures.)

Here is part of his summary of the whole year:

That negative studies continue to dominate the field, and that the positive ones still show decline in β-cell function over time, has led to more calls for combination approaches. When I [Dr. Skyler] have advanced such prospects at meetings of paediatric diabetologists, I hear groans. Yet when I have advanced these prospects at meetings of immunologists and transplant surgeons, I hear cheers.

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 (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 (late Feb)

Results from a phase-I Clinical Trial

Back in Sept 2009, Dr. Garg started a small pilot trial of Sitagliptin and Lansoprazole. These are two drugs currently used for type-2 diabetes, but this trial is aimed at using them on people who have type-1 diabetes.  The study was supposed to last about three months, and now they have published some results.

Summary:

The [treatment] lowered their mean blood glucose by about 12 mg/dL and their A1Cs by 0.27%, and they were able to cut their insulin dose by nearly 10 percent during the treatment period.

They are very happy with the results and plan to start a 120 person study.  You can see the government clinical trials registration here, although it hasn't started yet:

http://www.clinicaltrials.gov/ct2/show/NCT01227460

The improvement looks pretty small to me.  They are cheering about 12 BG points improvement?  A quarter point A1c?  10% less insulin?   So, for example, someone who is currently averages a BG of 150 might drop to 138.  An A1c might go from 7.5 to 7.25.  Instead of using 60 units of insulin a day, they might use 54.  I'm underwhelmed, and I hope they get bigger improvements in their phase-II studies.  On the other hand, Lansoprazole is a common antacid and is available over the counter, and while Sitagliptin is prescription, it is also very common.  I don't know the longest clinical trial run with either one of these drugs however.  I'm a little nervous that previous testing of Lansoprazole (the antacid) might just assume you take it once in a while.  I'd be real curious if anyone has seen what happened (even in animals) if you took it every day for a month, a year, 10 years, etc.  Since that is what is envisioned here.  I expect that is what will be learned from the phase-II and phase-III trials.

As far as this blog is concerned, I don't think I will continue following this research, because I think it looks like a treatment for diabetes, not a cure.  But I don't want to be too "down" on this research.  Up until now, different types of insulin has been the only treatment available for type-1s, so this might be the first step to having an array of drugs that help keep BGs more stable.  I know a lot of people would be very happy with a .75 or 1 unit change in A1c, and as a first test, this got 1/3 to 1/4 of the way there.  So maybe further development will get there.

Sources:

http://www.diabeteshealth.com/read/2011/01/07/7004/sitagliptin-januvia-lowers-blood-sugar-in-people-with-type-1-diabetes/

http://www.jdrftalk.org/2011/01/19/pilot-study-shows-popular-type-2-diabetes-drug-lowers-blood-sugar-levels-in-people-with-type-1-diabetes/

http://www.renalandurologynews.com/type-2-diabetes-drug-shows-promise-for-type-1/article/193749/

http://www.clinicaltrials.gov/ct2/show/NCT00978796

DiaPep277 Fully Enrolls a Small Phase-III Trial

DiaPep277 is a protein design to help train the body's immune system not to attack it's own beta cells.  It was the first treatment that I know of that started phase-III clinical trials, and has been in them for years.  There were two different phase-III studies underway, both about 300 people.  (Remember that for US or EU approval new treatments generally require two phase-III studies of about this size.)  However, the news story below is about a smaller "follow on" phase-III study with 40 people.  This study will follow people for 2 years after they were already part of the phase-II study.  It is looking at longer term safety/effectiveness issues.  Since it is fully enrolled, we "just" need to wait 2+ years for the results.  Of course the results from their mainline phase-III trials matter much more.

News: http://www.globes.co.il/serveen/globes/docview.asp?did=1000624744&fid=1725
Clinical trial: http://www.clinicaltrials.gov/ct2/show/NCT01281072

One Scam Cure and One Fringe Theory
Note that both of these guys cite Dr. Faustman's work, but are totally separate from it.  One of the "tricks" of scientific scams, is that it helps to cite real research, as part of your fraud.  So the fact that Drs. Arnim and Broxmeyer are citing Dr. Faustman says nothing about Dr. Faustman's work.

Ulrich von Arnim
If you ever wanted to know what a type-1 diabetes cure fraud would look like.  Here is your chance:
http://bva-tec.com/studien_en.php
And here is the news coverage.
http://www.theage.com.au/national/health-conman-strikes-again-20110209-1an2v.html
I'm not worried that this guy might have really cured type-1 diabetes: he's been in jail for two years for fraud, and has an arrest warrant waiting for him in Germany.  But it is interesting to look at his web site.  If that was your only source of information, you would think it was real.  The only tip-offs that I saw were these:

• If you look at the "clinical trial registration" number column, I can see that those are not European clinical trial numbers.  Nor are they American numbers.  I think they are European patent numbers (and patents are not the same as clinical trials!)  Also the first row that says "(pre-study)" so has no clinical trial number.  That's wrong: if they used people, they gotta have a clinical trial.  There are ethical and legal issues if they don't.  (It's possible that things were different in 1990-1992, but I don't think they were that different.)
• The second issue was the number of people "cured".  He claims to have cured about 14,000 people.  Now, there are about 1.5 million people with type-1 diabetes in the EU, so he has cured about 1% of them.  Already.  And we've never heard from even one of his patients.  Sounds nuts to me. (And he claims to have cured 1000s of people as long as 20 years ago, and no one has talked about this?)

Lawrence Broxmeyer
This guy has a fringe theory, or maybe a quack theory, that diabetes is caused by Tuberculosis (TB).  Actually, he has a lot of theories that a lot of different diseases are caused by TB.
http://lawrencebroxmeyer.wordpress.com/2011/01/26/diabetes-mellitus-tuberculosis-and-the-science-of-denial-by-dr-lawrence-broxmeyer/
If you believe this stuff, then it's obvious why a TB vaccine (like BCG) would cure type-1 diabetes.  He conveniently ignores the fact that giving BCG to people with type-1 diabetes does not cure them.  Nor does it prevent type-1 diabetes.  (In five or six previously completed studies.)


Random Reading / Listening

If you have a CD player in your car, I recommend a recorded lecture called "What is Wrong with Cloning?" by Dr. Arthur Caplan.  (The Sunnyvale, California, USA library has a copy.)  It is 1/3 a discussion of ethics, 1/3 the science of cloning and stem cells, and 1/3 stand-up comedy.  I have never laughed so hard while learning so much.  It's published by The Great Lecture Library.

This University PR piece:
http://www.ucsf.edu/news/2011/02/9428/type-1-diabetes-clinical-trials-aim-save-beta-cells-immunotherapies
describes three different clinical trials all being run out of UCSF by Dr. Steve Gitelman.
You can search my blog site for "Gitelman" to see previous coverage of these trials.

You might want to also look at this data, about longer life spans for type-1 diabetics dx recently vs. dx in the 1950s:
http://www.t1diabetes.nih.gov/Research_Accomp.pdf

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, 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
Web: http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials

Possible Cures for Type-1 in the News (Mid Oct)

Here is another collection of news from the last few weeks.


Teplizumab (by MacroGenics / Eli Lilly) Fails in phase-III Trials


It appears that MacroGenics lead phase-III trial of Teplizumab has failed.  Here are some quotes from their press release:

The Data Monitoring Committee concluded that the primary efficacy endpoint of the study, a composite of a patient’s total daily insulin usage and HbA1c level at 12 months, was not met 

Following careful evaluation of the Data Monitoring Committee’s recommendations for [this clinical trial], based on the lack of efficacy, [MacroGenics and Eli Lilly] have decided to suspend further enrollment and dosing of patients in two other ongoing clinical trials of teplizumab in type 1 diabetes: the Protégé Encore Trial, a second Phase 3 trial of the same design as Protégé, and the SUBCUE trial, a Phase 1b trial that is exploring the subcutaneous administration in patients with type 1 diabetes.

Discussion

Obviously, this is a huge blow to this drug as a possible cure for type-1.  MacroGenics might try to salvage this drug by reanalyzing the data from this experiment to see if there was a subpopulation which was helped.  But it is a long shot.

Another ominous question is what about similar drugs also under development?  Teplizumab is a monoclonal antibody targeting CD3 T-cells.  There are two other drugs in that category currently in clinical trials: Otelixizumab and NI-0401.  I don't know if Teplizumab failed because attacking CD3 is the wrong technique, or there was a problem specific to that one drug.  I hope the latter, because if it is the former, all three of these drugs will fail.  


The President and CEO of ToleRx (developers of Otelixizumab) has a blog ("The Green Chair") which you can read here:
http://www.tolerx.com/index.php?page=greenchair
His whole blog entry on this is worth reading. Here is his quote on this particular issue:

Next, I’d like to underscore some of the reasons why we continue to have a strong belief in our lead product candidate, otelixizumab. Otelixizumab’s biochemical structure is fundamentally different from other anti-CD3 monoclonal antibodies, such as teplizumab.  We believe this unique molecular structure is inherently important in mediating or delivering the “right” signals to T cells, and it is these signals, we believe, that are responsible for the effects, both in efficacy and tolerability, that were observed in our previous clinical trials. 

ToleRx expects to publish their phase-III results in the second quarter of 2011.

I haven't found any comment by Novimmune (makers of NI-0401).

Prior to this news, there were four treatments in phase-III of clinical trials aimed at curing type-1 diabetes.  And phase-III is the last stage before market approval. Teplizumab was one of these, and Otelixizumab is another.  NI-0401 is in phase-II clinical trials.    If you're a "glass is half empty" kind of person, you can say that this news has lowered the number of phase-III possibilities by 25%, and cast a pall over another 25%.  If you're a "glass is half full" kind of person, you can say that 5 years ago he had only one drug in phase-III trials, and even after this news, we still have three.  For myself, I would point out that over 30% of treatments in phase-III trials end up failing for one reason or other.  So of the four we had, we should expect 1 or 2 to fail.  And now, 1 has.

News article: http://www.reuters.com/article/idUSN2024945620101021
Press release: http://www.macrogenics.com/press_releases-284.html
Biz news article: http://www.bioworld.com/servlet/com.accumedia.web.Dispatcher?next=bioWorldHeadlines_article&forceid=56170

Sitagliptin and Lansoprazole Start a Phase-II Clinical Trial
I had previously blogged about this trial here:
http://cureresearch4type1diabetes.blogspot.com/2010/08/possible-cures-for-type-1-in-news-mid.html
but at the time they were planning the trial, but now they have started it:
http://www.clinicaltrials.gov/ct2/show/NCT01155284
These are two drugs currently used for type-2 diabetes, but this trial is aimed at using them on people who have type-1 diabetes.

Another Encapsulated Beta Cell Cure in Human Trials
I've been following LCT (encapsulated pig beta cells) for years, and just last month I found a second encapsulated beta cell trial (that one using human cells).  Now this month I found a third group doing encapsulated beta cell trials in people. Thanks to kisiliz (of CWD) for pointing this out to me:
http://www.lifescientist.com.au/article/222165/2010_sydney_project/?
http://care.diabetesjournals.org/content/32/10/1887.full

Unfortunately, the results of this phase-I study of about 14 people. (4 of whom were actually treated) were not good.  C-peptides were detected only immediately after the implantation.  Although slight amounts of generated insulin could be detected years later, Insulin usage and BG numbers did not change.  Basically, it was a proof of concept, but no practical impact.  However, this study was just published in 2009, so they might well improve things, and move forward.

This makes for a total of three encapsulated beta cell research teams active right now, and that's a good sign.


Below is Animal Research, so Years Away from Human Trials
I don't usually blog about research that has not started human trials, but I thought the following two research areas were particularly interesting.  Remember that anything that has not yet started clinical trials is well over 10 years away from general availability, and has a less than 50/50 chance of ever even starting human trials:

Alternate Artificial Pancreas Design
I would describe this as a "cool hack" (which is a software engineering way of saying "a really elegant design, which solves a complex problem in a simple way").  You can think of it as a hybrid of self dosing insulin and an implanted device.  If you prefer, you can think of it as an artificial pancreas with no moving parts or computer software.

The trick is as follows: you create an artificial pancreas, which is nothing more than an insulin reservoir, a chemical barrier, and a tube so the insulin (once it gets past the barrier) goes directly into the liver.  The barrier is key.  It reacts to the BG levels in blood to either let more insulin out, or less insulin.  This is very much like the "self dosing" insulins being researched by SmartInsulin and others, but it is different in that the "self dosing" chemistry is in a barrier which is separate from the insulin itself.  I don't know if this is a better or worse approach (than combining the self dosing chemistry into the insulin), but it is different.  And I believe that in early research, different is good,  because we don't care how many fail, just that one succeeds.  Sending the insulin straight to the liver is an interesting refinement as well.  Naturally generated insulin goes to the liver very quickly, before it circulates through the blood or is deposited in the fat cells under the skin.  So dripping the insulin into the liver should result in faster response, and in a sense is a more natural flow.  Injecting insulin in the fat just below the skin is very easy to do, with almost no training, which is why we do it, but that does not mean it is the best from a biological point of view, just that it is the most practical.

Since there are no batteries, moving parts, electronics, etc, this type of artificial pancreas should be much easier to care for as an implanted device, and have fewer parts that can break or need to be replaced.   Only insulin will need to be added.  Unfortunately, I have not found any published animal research on this device, but I haven't looked very hard (and I'm not so familiar with the tools to search for animal trials, as I am for human trials.) 

http://www.medicalnewstoday.com/articles/201455.php
http://onlinelibrary.wiley.com/doi/10.1002/jps.22138/abstract

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 (mid-Aug)

Sitagliptin and Lansoprazole Preparing for a Phase-II Clinical Trial
This trial is giving two drugs (both of which are already in use) to people with type-1 diabetes in their honeymoon phase.  The hope is that it will preserve some beta cell function.  This study is not yet recruiting patients.  They hope to recruit 54 patients and finish in April 2014. Sitagliptin is the generic name for Januvia, and Lansoprozole is the generic name for Prevacid.

A Little Discussion: I still don't understand why this is supposed to preserve beta cells.
When I blogged about the Sitagliptin only clinical trial, I said that I didn't understand why it might help type-1 diabetics; and I still don't.  With this trial, I don't understand why adding a antacid like Lansoprozole would help type-1 diabetics, either.  On the other hand, Januvia is available now for type-2 diabetes with a prescription, and Prevacid is available "over the counter" and as a generic.  So if this pans out, you will be able to get this as an "off label" use without waiting for further FDA approvals.

For me, a far more interesting trial, which I have blogged about before, is being run by the NIH, and which uses Diamyd plus Sitagliptin and Lansoprozole.  That one I understand: Diamyd stops the autoimmune attack by retraining it, and the other two drugs reverse beta cell damage or develop new beta cells.  You can read about that study here:
http://cureresearch4type1diabetes.blogspot.com/2010/02/diamyd-combo-phase-ii-trial-scaled-back.html
and I think they have upped the enrollment to 7 since I wrote that blog entry.  On the other hand, if this Sitagliptin and Lansoprozole only study lays a scientific foundation for more studies where they pair it with something to stop the autoimmune attack, that would be valuable.

News article: http://www.argusleader.com/article/20100811/NEWS/8110318/1001
Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT01155284

Other Phase-II trial of Sitagliptin: http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials#SitagliptinbyGarg
Blogging on Sitagliptin: http://cureresearch4type1diabetes.blogspot.com/search/label/Sitagliptin
Wikipedia for Sitagliptin: http://en.wikipedia.org/wiki/Sitagliptin
Wikipedia for Lansoprazole: http://en.wikipedia.org/wiki/Lansoprazole

Delay in Trucco's Phase-I Trial
Trucco's clinical trial is one of the first ones that I ever followed in my "status" web page.  That was years before I started my blog.  I've never blogged on it, because there has never been news.  Basically, they remove dentric cells, which are part of the immune system, treat those cells, and then put them back in the patient (the same patient where they came from).  This trial only enrolls people who have had diabetes for more than five years, so honeymooners are excluded.  It is a safety only study: they are not measuring any BG, A1C, insuline usage or C-peptide numbers.  If it turns out safe, then they plan to start a honeymooner only study to see if it improves any of those things. 

Now, finally, there is news.  In June 2010, Trucco's group updated their clinical trials record as follows:

Estimated Enrollment:	15
Study Start Date:	March 2007
Estimated Study Completion Date:	June 2011 (previously had been mid-2010)
Estimated Primary Completion Date:	December 2010 (previously had been mid-2009)

So this is basically a one year slip.

Web status page: http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials#TruccoatChildren%E2%80%99sHospitalofPittsburgh 
Year old newspaper article: http://durangoherald.com/sections/Features/Health/2009/08/24/Experiment_seeks_way_to_head_off_Type_1_diabetes_found_in_children/
Scientific Overview: http://www.mcgowan.pitt.edu/news/images/Trucco_PediatricDiabetes_2008.pdf
(Includes a nice diagram on page 8, even if the rest is highly technical.)

One Possible Cure, but not yet in Clinical Trials.
Some researchers in India are working with a "release as needed" injected insulin.  This is broadly similar to SmartInsulin.  A single injection of this new insulin, called Supramolecular Insulin Assembly II (SIA-II) resulted in good blood glucose levels (which they call "physiologic glucose levels") for over 100 days in animals.  I'm very much looking forward to what this does in people.  But remember: drugs generally take 10+ years to go through human trials, and less than half of the drugs successful in animals ever go on to human trials.  (Since this is an Insulin it might be slightly faster than 10 years, but not much.)

Abstract: http://www.pnas.org/content/107/30/13246.abstract
News report: http://www.dnaindia.com/india/report_india-develops-single-shot-insulin-for-diabetics_1409481

Another benefit of this drug, is that it puts pressure on the SmartInsulin developers.  In turn the SmartInsulin developers put pressure on the SIA-II developers.  I'm a firm believer that competition pushes both groups of developers to move faster, so I'm all for it.  It sounds to me like both SmartInsulin and SIA-II are close to starting human trials, but SmartInsulin is closer.

Discussion: What is a Cure?  Is this a Cure?
This drug (and also Smart Insulin) can start off an interesting parlor conversation about what is a cure?  Are treatments like SmartInsulin or SIA-II cures?   Obviously, each of us must make up their own mind about what is and is not a cure.  But in my mind, a treatment that required one injection every 3 months, and no blood glucose checks, no dietary limitations (no counting carbs), with no long term side effects and a normal life expectancy.  Personally, I would call that a cure, even though it requires an injection every 3 months, and even though you would have type-1 "on the inside".  It would be a functional cure.  Your opinion may differ.

News from Cerco Medical
I don't really cover Cerco Medical, because they have not yet started human trials for their "islet sheet", which is an encapsulated beta cell cure generally similar to LCT's  Diabcell.  However I know people are interested in it, and this is the most specific news I've heard about when they are hoping to start a clinical trial:

His [Scott R. King, president of Cerco Medical] company is planning to begin human testing in 2012 or 2013.  

This comes from a newspaper article, which is mostly about Artificial Pancreas work in Oregon:  http://www.oregonlive.com/health/index.ssf/2010/08/putting_blood-sugar_control_on.html


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 Diabetes in the News (October)

Living Cell Technologies Starts Phase-I Study in New Zealand

LCT is developing an encapsulated pig cell cure for type-1 diabetes. They have completed a phase-I study in Russia which resulted in one patient being off insulin for a few months, and another for a few weeks. They finally got approval from the New Zealand government, and have now treated their first patient. This clinical trial is very similar to the one they completed in Russia, but half the patients will get twice the dose that the Russians started with, and the second half will start out with three times the dose. Eight people total. This trial is scheduled to complete in January 2011.

Commentary
This research has already shown that their encapsulated cells can have good effect for short periods of time. The big question they need to answer are these:
1. Will larger doses of encapsulated cells results in less need for injected insulin?
2. How long will the encapsulated cells continue to work?
This trial will directly address question 1. By using higher doses, they will see if they get more generated insulin, and a higher percentage of people who are off insulin entirely. Unfortunately, question 2 can only be answered by time. By following the patients from the Russian trial and from this new trial for a year or two. Although it may be that they'll learn more about duration by starting with a higher dose.

Another issue for me is this: is this a phase-I study or a phase-II study? That's a big difference because a phase-II study moves them closer to general availability, while a second phase-I study doesn't. Officially the study is "Phase-I / Phase-II". It's size is 8 people, and that's on the small size of phase-I. However, it's goal is to try different doses, and that's a phase-II type of goal. (Phase-I is more focused on basic safety.) The real measure is how the US FDA views it, and I don't know the answer to that question.

Sources
http://www.clinicaltrials.gov/ct2/show/NCT00940173
http://www.lctglobal.com/downloads/cms_latest_news/2009-10-06-LCT%20NZ%20Implant%207%20Oct%2009%20.pdf
http://www.nzherald.co.nz/nz/news/article.cfm?c_id=1&objectid=10601771

LCT also issued their yearly report
which is here:
http://www.lct.com.au/downloads/cms_latest_news/2009-10-19-LCT%20Annual%20Report%202009.pdf

There are a couple of pieces of meaty news buried in this report.
On page 10 there is a list of KEY TARGETS. Nothing about any US trials, but (in addition to finishing their current trials) they list these two items:

• Commence pivotal trial in Russia.
• Commence DIABECELL® commercialisation [sic] – initially in Russian market.

And that makes it sound like whatever they are doing, they are going to do it in Russia first. They have a wholly owned subsidiary there, already.
Their clinical trials are described on pages 14 and 15.

Osiris Therapeutics Announces Preliminary Results For Prochymal Phase III GvHD and COPD Trials

Osiris is running two phase-III trials for their Prochymal treatment, for diseases other than type-1 diabetes. Both of these results are in and both were failures. They have several separate phase-II trials going on, and one of these does target type-1 diabetes. So having all their phase-III studies fail is bad news, but what really matters is the results of their type-1 diabetes clinical trial. Those results are expected in mid-2010.

press release: http://www.bioresearchonline.com/article.mvc/Osiris-Therapeutics-Announces-Preliminary-Res-0001?VNETCOOKIE=NO
http://www.clinicaltrials.gov/ct2/show/NCT00690066

Effects of Sitagliptin (Januvia) in Adult Patients With Type 1 Diabetes

This is a 20 person study which started in September and is expected to finish in December. It is trying a drug already in use for type-2 diabetics to see if it helps type-1 diabetics. This is aimed at helping type-1s use less insulin, not curing them. Based on my quick read of how this class of drugs works, I don't see why it's expected to work on type-1 diabetics. It helps the body create more insulin. I understand how that would help type-2s, but not type-1s. Anyway the proof is in the results, and we will not need to wait long. The research is being done at the Barbara Davis Center in Denver (which is top-of-the-line.) The good news is that we will have results very soon, and if they are positive, the drug is available right now.

http://www.clinicaltrials.gov/ct2/show/NCT00978796
http://en.wikipedia.org/wiki/Sitagliptin

Sernova's Animal Studies Continue

Sernova published results from some animal studies. You can read the links below for details. No date to start human trials was announced. This work is a follow on to Valdez's work in Mexico years ago, which was very controversial at the time it was done. He didn't do animal trials before going straight to people, and was eventually shut down by the Mexican government. It was also unclear if he was really getting as good results as he claimed. Sernova is trying to use the same ideas, but do the animal studies first, and then get Canadian or US FDA approval to do a clinical trial. So this treatment has been in clinical trials in the past, although not right now.

The basic trick was to get porcine beta cells, mix them with sertoli cells, and then implant the mix. Sertoli cells block the immune system, so the idea is that the immune system will not attack the new beta cells. So it's similar to encapsulated beta cells (LCT), but a little different.

http://www.genengnews.com/news/bnitem.aspx?name=65911061
http://www.benzinga.com/press-releases/m26601/sernova-s-cell-pouch-system-tm-and-sertolin-tm-preclinical-efficacy-presented-