Monday, April 26, 2010

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

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:
Clinical Trial Record:

Atorvastatin (Lipitor) completes enrollment of Phase-II Trial


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):

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:

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 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. :-)


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.

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:
Press release: 

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:

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:

I usually include a link to the abstract, and here it is:
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.

Wednesday, April 21, 2010

ToleRx Publishes Phase-II Data, 4 Year Follow Up

ToleRx In The News
Overview of what TolerRx is doing:
Previous blogging:

In January, ToleRx announced that their phase-III clinical trial of Otelixizumab was completely enrolled (which I previously reported on).  Now ToleRx has two more important pieces of information:

  1. They are going to start a second phase-III clinical trial, called DEFEND-2.
  2. Publishing 4 year follow up data on an earlier phase-II clinical trial (called TTEDD).

The second phase-III clinical trial is important because you need two successful trials for US FDA or EU EMEA approval.  So the sooner they start that second trial the sooner they can get approved. 

The 4 year follow up data is important, because it can tell us how well it works.  Remember that the goal of TTEDD was to determine the best dosing system for the phase-III trials, so we should expect better results from the phase-III trials, and lower side effects, then reported on here:

Treatment with ChAglyCD3 delayed the rise in insulin requirements of patients with recent-onset diabetes and reduced its amplitude over 48 months (+0.09 vs +0.32 U/ kg/ day in the placebo group). Using multivariate analysis this effect was correlated with higher baseline residual beta cell function and a younger age.

For an example of what this means,  if you assume a kid who weighs about 50kg, at the end of 4 years, they might have increased their insulin usage by about 16 units.  However, those that received the treatment only increased their usage by about 5 units.  Both went up, but the untreated patients went up a lot more.

Another issue for new drugs is safety, and here the news is good:
In this reported study, otelixizumab administration was associated with transient symptoms during dosing including flu-like syndrome and transient perturbation of Epstein Barr Virus (EBV).  During the 48 months of follow-up there were no EBV related symptoms, no higher incidence of infections, and no lymphoproliferative or other types of cancer observed.  Following the 18 month efficacy results of the present study, Tolerx has optimized the otelixizumab dosing regimen to minimize adverse events, with encouraging data on clinical effect.
Which I translate as: some people got flu like symptoms during treatment, but there were no long term side effects at all. Note that about 40 people were treated, and this was a 4 year follow up, so this will not close the book on safety issues, but it is clearly good news.

One interesting tid-bit is that the TTEDD study is not limited to honeymoon diabetics, although the follow on (DEFEND-1 and DEFEND-2) studies are.  Because the earlier study is open to non-honeymooners, but the later studies are not, I think it is reasonable to assume that this treatment did not work well for non-honeymooners.  However, it would interesting to see compare the TTEDD data for honeymooners vs. non-honeymooners.  The TTEDD study is still recruiting new patients.

Press Release:
Company Blog:
Clinical Trial Record:

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