Tolerx And GlaxoSmithKline Announce Phase 3 Defend-1 Study Of Otelixizumab In Type 1 Diabetes Did Not Meet Its Primary Endpoint

Main Category: Diabetes
Also Included In: Clinical Trials / Drug Trials;  Pharma Industry / Biotech Industry
Article Date: 12 Mar 2011 - 1:00 PDT

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Tolerx, Inc. and GlaxoSmithKline (GSK) 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.

Source: Tolerx, Inc

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