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.

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

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

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

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

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

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

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


Atorvastatin (Lipitor) completes enrollment of Phase-II Trial

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

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

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

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

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

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

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

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

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


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

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


I think the biggest news now is this paragraph:

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

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


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

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

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

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

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

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

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

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

Joshua Levy

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

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

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

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

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


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


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

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

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


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

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


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

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

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

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

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

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


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


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


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

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

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

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

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

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

Tolerx Completes Enrollment in Phase-III Otelixizumab Trial

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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


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

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

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

MicroCHIPS Will Start phase-I Trial of new CGM (and gets 16+ million)

For people interested in the artificial pancreas project, MicroCHIPS just got about 16 million dollar investment, and one of the things they will do with that money is start a phase-I study later in 2010 on their CGM technology. Here is their description of why their technology is better than current technology:

MicroCHIPS hopes their product will last months, or even years, and their main innovation is to create the implant with a differently-built sensor. Current devices, Pax says, have a single sensor that can only detect glucose levels until it runs out of the sensing chemical. But the MicroCHIPS device employs a redundant array of sensors, with each one becoming active as needed.

And the part that interests me the most is this:

MicroCHIPS intends to conduct initial clinical testing in 2010 to advance its diabetes program.

Some Discussion

I think it is clear that CGM technology is the weakest component in current artificial pancreas research. However, a CGM technology that lasted 3 months or more in the body would be a huge improvement in this area. So I'm excited by this technology, and am looking forward to seeing how well it works. One of the new funders is Medtronic. Since Medtronic already has cutting edge commercial CGM technology, they are not expecting more of the same: they are expecting better than they have. So I think it is fair to expect that whatever MicroCHIPS is creating, it is a lot better than we have now.

Press Release: http://www.mchips.com/10_Jan_07_pr.html
News Article: http://www.dotmed.com/news/story/11267/

Novo starts phase-II Clinical Trial of oral GLP-1

Novo Nordisk (one of the largest pharma companies targeting type-1) is working with Hvidovre University Hospital in Denmark to test an pill version of Victoza (generic: Liraglutide) which is a GLP-1 receptor agonist. They are specifically targeting type-1 diabetics in this study. Technically a phase-II trial (because the drug is already approved), it will enroll about 30 people, and be completed by second half of 2010.

A Little History

Several treatments leveraging GLP-1 have been tried over the years as GLP-1 related drugs help the pancreas generate more insulin. They are usually targeted at type-2 diabetics, who have a lot more useful pancreas to work with. Byetta is the most famous GLP-1 analog used by type-2 diabetics. Of course, the question here is: will it help people with type-1 diabetes?

Some Discussion

This is right on the edge of what I consider a possible "cure". It seems unlikely to me that any treatment that works by causing the pancreas to generate more insulin will -- by itself -- result in a cure for type-1 diabetes. However, I'm reporting on this because it might turn out to be part of a cure. For example, by combining it with Diamyd's, ToleRx's or MacroGenic's treatments (all in phase-III clinical trials, and all of which prevent/weaken the autoimmune attack) .

The injected form of this drug (Victoza) was approved for use in the EU in 2009, and is marketed in at least three countries (UK, Denmark, and Germany). However it has not been approved in the US, because of worries about thyroid tumors. The US FDA review was in April 2009.

If this drug turns out to help type-1 diabetics, then (in addition to Byetta) there are two other similar drugs, each being developed by a different drug company, which may also help type-1 diabetics: albiglutide and taspoglutide.

Press Release: http://www.reuters.com/article/idUSLDE60C0CB20100113?type=swissMktRpt
Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT00993720
Wikipedia: http://en.wikipedia.org/wiki/Liraglutide

News (but no Announcement) from Faustman

Although Faustman's team has not made an official announcement (at least not one that I've seen), they did reopen enrollment in their phase-I BCG clinical trial, after having closed it last February. Without information on why they did this, there is no way to know if this is good news or bad, or if it will cause a delay in reporting their phase-I results. Although you'd think if it was good news they would have had an announcement.

This is the timeline: In Feburary 2009 they updated their clinical trial record to show that they had finished enrollment in their phase-I trial. In mid 2009 they announced that their results would be published in early 2010, and specifically would be turned over to their internal statistics group in November of 2009. However, in October 2009 they updated their clinical trial record again to show that they were once again enrolling patients in the study. Right now, their web site says specifically they are NOT enrolling new patients, but their Clinical Trials web page says that they ARE enrolling new patients.

What might this mean? The best possible news would be that they are trying to do more with their phase-I trial than originally expected. LCT did this for their trial in Russia. Once it was underway, they updated it to include more people and bigger doses. If the BCG team is trying the same thing, that would be good news.

The worst news would be that they did some early data analysis of their results, and found they did not have statistically significant results. So they added more people to the study in the hopes of getting a statistically significant result. The DiaPep227 guys did this with their phase-III study.

Middle of the road news would be that some of their samples or data got lost, mislabeled, or a patient pulled out at the last minute or something. So they need some more patients to enroll, and might have a delay, but nothing really bad. Something like this happened to Diamyd's phase-II LADA trial.

Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT00607230

JDRF, J and J's Animas Corp, and DexCom Start Joint AP Project with Clinical Trial this Year

For people interested in the artificial pancreas project, there was a big announce from JDRF of a joint project with Animas (pump makers, and a division of Johnson & Johnson), and DexCom (CGM makers). It's been widely publicized, so I won't go into details. To me, the most interesting part was this:

The first patient testing could begin in less than a year, Kowalski said.

and that is good news, especially since most phase-I AP testing can be done quickly. We should start seeing clinical trial results on this AP combination maybe by end of this year, but more likely sometime next year.

News Article: http://abcnews.go.com/Business/wireStory?id=9550823

Joshua Levy

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

Diamyd Finishes Enrollment of their European Phase-III Trial

Diamyd has finished enrolling patients in their 300 person, phase-III European trial. Diamyd is a vaccine like treatment designed to train the body's immune system not to attack itself and is focused on GAD65, which is the most common antibody marker carried by people with type-1 diabetes. Several human trials have already completed, and several more are in process. This trial is newly diagnosed type-1 diabetics, only.

Why is finishing enrollment important? For a couple of reasons:

1. Once a trial is fully enrolled, everyone knows when it will end, or at least when they will finish gathering the required data. So in a very real sense, we can see the end of the tunnel now. This trial lasts 15 months, so the last person who enrolls in Nov-2009 will finish with the protocol in Feb-2011.
   
2. Phase-III is the last phase before marketing approval of a new drug, so these guys are now the treatment second closest to general availability. (DiaPep227 Phase-III fully enrolled a few months ago.)

These guys also have a similar, large phase-III trial going on in the US, and they are still recruiting for that one. Plus, there are other clinical trials by different people using the same drug.

More info:
http://www.pipelinereview.com/index.php/2009111230708/Vaccines/Diamyds-European-Phase-III-Study-Fully-Recruited.html

Exsulin Update: Vague Results and Another Phase-II Trial Starting

This news is actually from the Summer, but I haven't blogged about it before, so here it is:
Here is the highlight of the results from their last batch of clinical trials:

In the T1DM study (SPIRIT 1), Arginine-stimulated C-peptide (AUC0-30) significantly increased from baseline in the 600 mg group (p = 0.0058 versus placebo)

My translation: the treatment caused people to generate more of their own insulin in response to a meal, when given 600mg. There was a second group that got 300mg, but they did not see any benefit. The full paper includes more detail one what was seen, but it looked pretty small to me.

Of course, the good news, is that this clinical trial only took them a few months to run, so they could easily make improvements to their process, and try it again. And that is what they are going to do:

The new phase-II trial is already recruiting it's 30 participants and they are hoping to have results by Q2 2010. Because INGAP does not stay in a person's system for very long, in this trial they will give smaller doses three times a day (rather than larger doses once a day), and therefore hope to have better effects and fewer side effects. They have also changed the formulation to have less irritation at the injection site. In their previous study, 25% of the people who got the higher dose, dropped out of the trial because of "adverse effects" (often this irritation), so that is a problem they want to address.

Abstract of research of completed phase-II trail:
http://www3.interscience.wiley.com/journal/122518238/abstract

Press release:
http://www.medicalnewstoday.com/articles/161069.php

Clinical Trial record for new phase-II trial:
http://www.clinicaltrials.gov/ct2/show/NCT00995540

I want to particularly thank fellow BraveBuddy Ricardo Dolmetsch for providing a lot of of the information that I used to report results from the previous trial and for providing some useful insight. Also thanks to ChildrenWithDiabetes member Ellen for pointing out the second phase-II study.

Phase-II Results from DiaPep227

DiaPep227 entered phase-III trials before I started to track clinical trials, so I've never blogged about their Phase-II results. However, since they're phase-III was the first to be fully enrolled, I thought it might be interesting to look at their previous results. Here is the quote from their abstract:

At 18 months, stimulated C-peptide concentrations had fallen in the placebo group (p = 0.0005) but were maintained in the DiaPep277 group. The need for exogenous insulin was higher in the placebo group than in the DiaPep277 group. Mean HbA_1c concentrations were similar in both groups. After extension of the study, patients continuing treatment with DiaPep277 and those switched from placebo to DiaPep277 manifested a trend towards a greater preservation of beta-cell function compared to patients maintained on or switched to placebo. The safety profile of DiaPep277 was similar between the treatment and placebo groups, and no drug-related adverse events occurred.

When I look at that summary, the first thing that I notice is that there are no numbers in the results (except a p value, which isn't a result, its a measurement of a result). It talks about C-peptide and A1C numbers, but does not give them. For me that is a big red flag. Vague qualitative statements ("need for exogenous insulin was higher") don't give me confidence. I want to know how much more insulin? And I don't see that data here. Exsulin's abstract in the news item above had the same problem, and reading the whole paper just reinforced by belief that no numbers in the abstract does not bode well for the strength of the results.

The complete paper is pay-per-view, so I'm just working off the abstract.

Abstract of research:
http://www3.interscience.wiley.com/journal/113488533/abstract

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

Possible Cures for Type-1 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-

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

This is an experiment in "quick hits". I will provide a paragraph or two of information on recent news items about possible cures for type-1 diabetes. So, in no particular order, here we go:

Andromeda Completes Patient Recruitment in Phase III Trials for DiaPep 227

Andromeda has announced that their phase-III clinical trial of DiaPep277 is fully enrolled. This is an important milestone, because it now means the end of the study can be predicted. Since their protocol is 2 years long, they will be data complete around September 2011. They have also said that they will have results at end of 2011, which makes sense.

DiaPep277 is the oldest Phase-III clinical trial that I know of. Previous news has not been good. Their intermediate results were lackluster and they changed their experimental design and recruited more patients. I've never gotten around to reviewing their Phase-II results (which were published prior to my interest in clinical trials), but maybe I should.

Press release: http://www.pipelinereview.com/index.php/2009090929254/Proteins-and-Peptides/Andromeda-Biotech-Successfully-Completes-Patient-Recruitment-in-Phase-III-Trials-for-its-Lead-Drug-DiaPep277-for-Type-1-Diabetes.html

4-Year Follow-up of Diamyd(r) Phase II Study Shows Clear Positive Trend

Diamyd got permission to extend their Phase-II trial, and continue to follow the same group of patients for a total of 7 years. They talked about 4-year data in this way:

Initial analysis of new data shows, that patients treated with
the Diamyd(r) vaccine early after diagnosis have a clearly better diabetes
status compared to the corresponding placebo group, still 4 years after the
injections.

Since there are no actual numbers here, I wouldn't read too much into it. "Clearly better" is pretty vague. There is no reference to anything published, so there is no place to look for more details or actual numbers.

press release: http://www.reuters.com/article/pressRelease/idUS86571+03-Sep-2009+GNW20090903

Diamyd to include children over 10 yrs in US phase III study with Diamyd diabetes vaccine

Diamyd got FDA approval to lower the minimum age of enrollment in their US Phase-III study down to 10. That's young for a clinical trial, and a sign that the FDA thinks that Diamyd's treatment is very likely to be very safe. For comparison, ToleRx can accept people as young as 12, and MacroGenics down to 18 (and even 8, but only with special approval).

press release: http://www.pharmabiz.com/article/detnews.asp?articleid=51470&sectionid=

Faustman is Data Complete, Results by early 2010.

In 10-February 2009, the Nathan/Faustman group officially reported that they had enrolled the last patient into their Phase-I trials. They also updated their clinical trial record to show that they would be data complete in July 2009. (This makes sense, since the protocol only requires 3 months of data gathering after a patient starts.)

So, as of now, they should be working on analyzing the data, writing the paper, and getting it published. (And if we are lucky, getting reporters or bloggers to write about the results!)

They also have a facebook page which contains this quote:
"We hope to have all of the Phase I data submitted to our biostatistics center in November 2009", and their lab web pages talks about having results by early 2010, so I think we are close to hearing about their results. Their just-released newsletter also has the "early 2010" date.

Joshua Levy