Phase III study will evaluate effects of otelixizumab, an investigational anti-CD3 monoclonal antibody, on preservation of endogenous insulin secretion Tolerx, Inc., a biopharmaceutical company engaged in the discovery and development of novel therapies for immune-mediated diseases, today announced that it is proceeding toward the initiation of a Phase III study of otelixizumab in new-onset type 1 diabetes. Tolerx is initiating this pivotal trial after reviewing the results of the otelixizumab development program with the US Food and Drug Administration (FDA) at an End of Phase II meeting.
The Phase III study, known as DEFEND (Durable Response Therapy Evaluation For Early or New Onset Type 1 Diabetes), will be conducted at multiple centers in North America and Europe and will evaluate whether a single course of otelixizumab reduces the amount of administered insulin required for control of blood glucose levels by inhibiting destruction of beta cells. Maintenance of beta cell function has been associated with improved glycemic control (HbA1c levels), fewer hypoglycemic events and reduction of long term disease complications in established diabetics in the Diabetes Control and Complications Trial (DCCT). DEFEND enrollment is expected to begin mid-2008.
“We are very pleased with the outcome of the End of Phase II meeting with FDA and the opportunity to advance initiation of the DEFEND trial. This step is a significant and important milestone for Tolerx,” said Dr. Douglas J. Ringler, President and Chief Executive Officer of Tolerx. “The rigorous science behind our Phase II clinical program has provided us with valuable insights that facilitated our moving forward into DEFEND with an optimized dosing regimen that has the potential to transform the treatment paradigm for type 1 diabetes.”
“We have worked closely with FDA over several years to ensure that the design and endpoints of DEFEND reflect the mechanism of action of otelixizumab and are relevant and appropriate in evaluating whether otelixizumab may benefit subjects with new-onset type 1 diabetes. In February, 2008 FDA released new draft guidance on developing drugs for diabetes mellitus and DEFEND incorporates key measures described within the guidance, in particular, stimulated C-peptide levels as a primary efficacy endpoint,” said Dr. Lou Vaickus, Chief Medical Officer at Tolerx.
Otelixizumab is a monoclonal antibody that binds to CD3, a T lymphocyte receptor involved in normal cell signaling. Otelixizumab is thought to work by blocking the function of T effector cells that attack the body’s tissues and cause autoimmune disease while inducing a subset of T cells known as T regulatory cells. It is thought that the T regulatory cells may protect against T effector cell damage well after the drug has been eliminated from the body. Tolerx is continuing to evaluate otelixizumab in subjects with type 1 diabetes in TTEDD (TRX4 Therapeutic Evaluation of Different Dosing Regimens), an ongoing Phase II study. A principal purpose of TTEDD was to evaluate different dosing regimens in an effort to reduce side effects and to learn more about otelixizumab’s activity. Tolerx has conducted dose optimization studies in type 1 diabetes and has identified a dosing regimen that thus far has significantly reduced side effects while maintaining important biological activity. This dosing regimen will be used in our Phase III pivotal trial DEFEND.
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