ToleRx Publishes Phase-II Data, 4 Year Follow Up

ToleRx In The News
Overview of what TolerRx is doing: http://joshualevy.pbworks.com/DiabetesCureReadyForHumanTrials#OtelixizumabbyToleRx
Previous blogging: http://cureresearch4type1diabetes.blogspot.com/search/label/ToleRx

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.

Abstract: http://www.springerlink.com/content/p3572576j25l2640/
Press Release: http://www.prnewswire.com/news-releases/single-short-course-of-tolerxs-otelixizumab-provides-prolonged-preservation-of-beta-cell-function-87773937.html
Company Blog: http://www.tolerx.com/index.php?page=greenchair
Clinical Trial Record: http://www.clinicaltrials.gov/ct2/show/NCT00451321

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