Tolerx and GlaxoSmithKline (GSK) said the phase III 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 program for otelixizumab.  New recruitment and dosing in the DEFEND-2 study, the ongoing confirmatory phase III 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 CEO 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."

DEFEND-1 was a randomized, placebo-controlled phase III 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 eight-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 FDA and the American Diabetes Association.