Tolerx and GlaxoSmithKline Announce Phase 3 Defend-1 Study of Otelixizumab in Type 1 Diabetes Did Not Meet Its Primary Endpoint

CAMBRIDGE, Mass. and LONDON, March 11, 2011 /PRNewswire/ -- Tolerx, Inc. and GlaxoSmithKline (GSK) today announced that the Phase 3 DEFEND-1 study of otelixizumab, an investigational humanized anti-CD3 monoclonal antibody, did not meet the primary efficacy endpoint of change in C-peptide at month 12 in patients with new-onset autoimmune type 1 diabetes.  

Following preliminary review of the data, no new or unexpected treatment-related safety concerns have emerged during the DEFEND-1 study. Study investigators and regulatory agencies have been notified of the DEFEND-1 study outcome.

GSK will continue to explore additional dosing regimens to inform decisions about the future clinical development programme for otelixizumab.  New recruitment and dosing in the DEFEND-2 study, the ongoing confirmatory Phase 3 study with a design similar to DEFEND-1, has been suspended pending review of the DEFEND-1 results.

"While we are disappointed in the DEFEND-1 results of otelixizumab, we remain committed to the development and commercialization of the candidates in our pipeline, each of which has a distinct mechanism and target for correcting abnormal immune responses," said Douglas J. Ringler, VMD, President and Chief Executive Officer of Tolerx. "Our immunotherapy candidates represent some of the latest scientific advances in harnessing the immune system for therapeutic benefit, including TRX518 which is a showpiece of our pipeline as an immunotherapy to treat cancer."

"Clearly these are disappointing data, but we are committed to working with Tolerx to better understand the results of this study and determine the way forward," said Jackie Parkin, Medicines Development Leader, GlaxoSmithKline.

Tolerx Pipeline

In addition to otelixizumab, Tolerx has four product candidates in various stages of development, and each candidate is based on Tolerx's immunology expertise in understanding how therapies can be designed to normalize the immune system. These other product candidates in Tolerx's pipeline are:

• TRX518, an immunotherapy in Phase 1 development for cancer, targets and activates the glucocorticoid-induced tumor necrosis factor receptor (GITR).
• TRX1, a nonlytic anti-CD4 antibody that has completed early stage clinical studies and is currently being evaluated for the treatment of undesirable or aberrant humoral (anti-body-related) immune responses..
• TRX585 and TRX385, that enhance immune responses by targeting the immunoglobulin-like transcript (ILT) family of receptors, are being evaluated for the treatment of cancer and viral disease.

About the DEFEND-1 Study

DEFEND-1 is a randomized, placebo-controlled Phase 3 study of 272 patients, age 12 to 45, with new-onset type 1 diabetes. DEFEND-1 was conducted at over 100 study centers throughout North America and Europe. The study was designed to evaluate whether a single 8-day intravenous course of otelixizumab (3.1mg), administered not more than 90 days after the initial diagnosis of autoimmune type 1 diabetes, preserved the function of insulin-producing beta cells in the pancreas, as measured by C-peptide. Measurement of C-peptide (a protein that shows how much insulin the body is producing) at 12 months after dosing was the primary endpoint in DEFEND-1 and is a well established surrogate measure of beta cell function and a recommended endpoint by the U.S. Food and Drug Administration (FDA) and the American Diabetes Association.

About Otelixizumab

Otelixizumab, an investigational humanized anti-CD3 monoclonal antibody, is a targeted T cell immunotherapy 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.

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 the Tolerx-GSK Collaboration

In October 2007, Tolerx and GSK established a worldwide alliance to develop and commercialize otelixizumab for a range of autoimmune and immune-mediated inflammatory diseases, including type 1 diabetes. Under the terms of the agreement, Tolerx is responsible for the clinical and regulatory activities for otelixizumab in type 1 diabetes in the US. Tolerx has the option to co-promote otelixizumab in type 1 diabetes in the US with GSK, while GSK has exclusive rights to develop and commercialize otelixizumab in all other indications in the rest of the world. GSK also has the exclusive right to develop the pediatric indication for type 1 diabetes in the US.

About Tolerx

Tolerx, Inc., a biotechnology company and world leader in immunology, has a portfolio of innovative, first-in-class therapeutic candidates to treat autoimmune diseases, cancer and viral infections by normalizing immune responses. Tolerx is a privately held company headquartered in Cambridge, MA USA. For more information, please visit www.tolerx.com.

GlaxoSmithKline – one of the world's leading research-based pharmaceutical and healthcare companies – is committed to improving the quality of human life by enabling people to do more, feel better and live longer.  For further information please visit www.gsk.com  

GlaxoSmithKline cautionary statement regarding forward-looking statements

Under the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995, GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Factors that may affect GSK' s operations are described under 'Risk Factors' in the 'Business Review' in the company' s Annual Report on Form 20-F for 2010.

SOURCE Tolerx, Inc.