Tolerx presents data from otelixizumab Phase 3 DEFEND-1 clinical trial in type 1 diabetes patients

Jun 28 2010

Tolerx, Inc., a biopharmaceutical company developing novel therapies to treat autoimmune diseases and cancer by modulating T cell activity, today presented an analysis of baseline data from the Phase 3 DEFEND-1 clinical trial of otelixizumab in patients with autoimmune new onset type 1 diabetes.  The analysis showed that higher C-peptide levels had a statistically significant correlation with a decrease in two distinct measurements of glucose variability, confirming that C-peptide is a robust clinical marker for beta cell function which becomes impaired in type 1 diabetes.  Measurement of C-peptide has been endorsed by FDA as the primary endpoint for clinical trials of therapies that are designed to preserve beta cell function in new-onset type 1 diabetes and is the primary endpoint to evaluate the efficacy of otelixizumab in the DEFEND-1 clinical trial, with results from DEFEND-1 expected in the first half of 2011.  

The pre-dose baseline data from DEFEND-1 represents one of the first comprehensive studies to correlate higher C-peptide levels with lower blood glucose variability in patients with type 1 diabetes.  These results are clinically meaningful because blood glucose variability may be a risk factor for short- and long-term complications, including severe hypoglycemia and microvascular disease, in patients with type 1 diabetes.  The analysis from the DEFEND-1 study was presented at a poster session of the 70th Scientific Sessions of the American Diabetes Association (ADA) taking place June 25 through June 29 in Orlando, Florida. 

"We are gratified that the analysis of baseline data from our DEFEND-1 clinical trial may contribute to a better understanding of new-onset type 1 diabetes and to clinically meaningful outcomes for patients.  It is compelling that these data showed a strong correlation between blood glucose variability and C-peptide, particularly because glucose variability was measured with basic finger stick blood glucose testing. Tolerx is seeking additional and more robust data from the ongoing confirmatory Phase 3 DEFEND-2 study in which all subjects will wear a continuous glucose monitor (CGM) at regular intervals," said Aoife Brennan, MD, endocrinologist and Associate Medical Director at Tolerx.  "Our Phase 3 DEFEND-1 and DEFEND-2 clinical trials aim to show that otelixizumab is not only safe and well tolerated, but that it preserves beta cell function."

The Tolerx data presentation at ADA (abstract #700-P), entitled "Lower C-Peptide Secretion Is Associated With Increased Blood Glucose Variability In Adults With New-Onset Type 1 Diabetes: Analysis Of Baseline Data From DEFEND-1," reviewed data from patients within 90 days of diagnosis with new-onset diabetes, monitoring their blood glucose 7 times per day for 7 days prior to the date when the patients began dosing with Tolerx's investigational product candidate, otelixizumab. Two measurements of glucose variability were evaluated for relationship to C-peptide: average daily risk range (ADRR) and mean amplitude of glycemic excursions (MAGE).   With a decrease in each measure of glucose variability, ADRR and MAGE, there was a statistically significant correlation with an increase in C-peptide.  The results demonstrate the relationship between glucose variability and C-peptide, confirming that C-peptide is a robust and important clinical marker for beta cell function and glycemic control.