Tolerx Presents Baseline Data from DEFEND-1 Study Demonstrating that More Convenient Fasting C-Peptide Test Yields Comparable Results to Standard Diagnostic Test for Type 1 Diabetes

STOCKHOLM, Sept. 23 /PRNewswire/ -- 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 fasting C-peptide, as measured by results from a single blood draw, were highly correlated with maximum stimulated C-peptide, as measured by results of multiple blood draws over approximately two hours.  The results from the DEFEND-1 analysis showed the utility of a more convenient, single blood draw test of fasting C-peptide as a valid measurement of residual beta cell function in patients with type 1 diabetes, when compared with results from the conventional post-meal maximum stimulated C-peptide test.  The analysis from the DEFEND-1 study was presented at a poster session of the 46th Annual Meeting of the European Association for the Study of Diabetes (EASD) taking place September 20 through September 24 in Stockholm, Sweden. 

The pre-dose baseline data from DEFEND-1 represents one of the first comprehensive studies to correlate fasting C-peptide with post-meal maximum stimulated C-peptide in patients with new onset type 1 diabetes.  In the study analysis, the correlation of fasting C-peptide and maximum stimulated C-peptide were statistically significant (p<0.0001) and age group had no significant effect on this association.  The FDA has identified measurement of C-peptide compared to control at 12 months as a primary endpoint for clinical trials of therapies that are designed to preserve beta cell function in new-onset type 1 diabetes.  C-peptide 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.  

"With potential new therapies on the horizon for intervening early in the type 1 diabetes disease process, it is becoming increasingly important to find easier and more convenient ways for early diagnosis of patients," said Paolo Pozzilli, MD, Professor of Endocrinology & Metabolic Diseases at the University Campus Bio-Medico in Rome, Italy.  "These data from the DEFEND-1 analysis show that fasting C-peptide, which can be measured from a single blood sample taken in the doctor's office, may be useful in measuring beta cell function and predicting stimulated C-peptide."

"We are gratified that this analysis of baseline data from our DEFEND-1 clinical trial may contribute to our understanding of beta cell function in new onset type 1 diabetes and help in designing more efficient clinical trials," said Aoife Brennan, MD, endocrinologist and Medical Director at Tolerx.  "As Tolerx moves forward with our Phase 3 DEFEND-1 and DEFEND-2 clinical trials to evaluate otelixizumab as a potential new treatment option, we are also able to collect and analyze data that can identify patients with type 1 diabetes who may benefit from early interventions in their disease process."

The Tolerx data presentation at EASD (Poster # 460), entitled "Fasting and stimulated C-peptide at baseline in DEFEND-1, a Phase 3 study of otelixizumab in new onset type 1 diabetes," reviewed data from 343 adults and 36 adolescents who were screened for participation in the DEFEND-1 clinical study.  The patients were administered two diagnostic tests: the fasting C-peptide test as measured by results from a single blood draw, and the post-meal maximum stimulated C-peptide as measured by results of multiple blood draws over approximately two hours.  

About the DEFEND Studies

The DEFEND studies are randomized, placebo-controlled, Phase 3 trials designed to evaluate the efficacy and safety of otelixizumab following a single course of treatment in subjects with newly diagnosed autoimmune type 1 diabetes, aged 12 to 45 years. The primary endpoint in both studies is C-peptide at 12 months after dosing. C-peptide is a surrogate measure of beta cell function and a recommended endpoint by the U.S. Food and Drug Administration (FDA) and the American Diabetes Association. Maintenance of beta cell function has been associated with improved glycemic control (HbA1c levels), fewer hypoglycemic events, fewer hyperglycemic excursions, and a reduction in long-term disease complications in established type 1 diabetes patients, as referenced in the Diabetes Control and Complications Trial (DCCT). The studies are being conducted in North America and Europe. DEFEND-1 has achieved its target enrollment of 240 subjects, with preliminary data expected in the first half of 2011. DEFEND-2 is designed to enroll up to 365 subjects; enrollment is ongoing.

For more information about DEFEND, please visit www.DefendAgainstDiabetes.com.

About Type 1 Diabetes

Diabetes (medically known as diabetes mellitus) is the name given to disorders in which the body has difficulty regulating its blood glucose (sugar) level.  There are two major types of diabetes:  type 1 and type 2. Type 1, previously known as juvenile diabetes or insulin-dependent diabetes, is a disorder involving the body's immune system.  In type 1 diabetes, the immune system attacks and destroys the insulin-producing beta cells in the pancreas.  As a result of the decrease in endogenous (natural) insulin production, patients must monitor their glucose levels frequently and administer insulin regularly to control their blood glucose levels. 

About Otelixizumab

Otelixizumab is a targeted T cell immunomodulator being developed for the treatment of type 1 diabetes and other autoimmune diseases.  Otelixizumab targets CD3, a T lymphocyte receptor involved in normal cell signaling.  Otelixizumab has not yet been approved for marketing. Data suggest that the antibody may work in patients with type 1 diabetes who have residual beta cells by blocking the function of effector T cells that mistakenly attack and destroy insulin-producing beta cells, while stimulating regulatory T cells that are understood to protect against effector T cell damage, thus preserving the beta cells' ability to make insulin. 

About Tolerx

Tolerx, Inc., a world leader in the understanding of T cell function, is developing novel therapies intended to treat autoimmune diseases, diabetes, and cancer by specifically modulating T cell activity.  The company's pipeline includes its lead candidate, otelixizumab, a targeted T cell immunomodulator in Phase 3 development for the treatment of type 1 diabetes that is partnered with GlaxoSmithKline.  TRX1, a Phase 1 candidate, is a nonlytic anti-CD4 antibody that is being developed for the treatment of aberrant or untoward immune responses.  The company also has three pre-clinical candidates, TRX518, TRX585 and TRX385, that enhance immune responses and as such are being evaluated for potential benefit in the treatment of cancer and chronic infections. Tolerx is a privately held company headquartered in Cambridge, MA, USA.  For more information, please visit www.tolerx.com.

SOURCE Tolerx, Inc.