GSK diabetes drug fails phase III study

An investigational therapy for diabetes being developed by GlaxoSmithKline (GSK) in partnership with the immunology-focused biotech company Tolerx failed to meet the primary efficacy endpoint in a phase III clinical trial, according to the companies.

Otelixizumab, a humanised anti-CD3 monoclonal antibody, did not deliver the hoped for change in C-peptide at month 12 in patients with new-onset autoimmune type 1 diabetes.

The study, known as DEFEND-1, was conducted at more than 100 US and European centres and enrolled 272 patients between the ages of 12 and 45 with new-onset type 1 diabetes. The research tested whether a single eight-day intravenous course of otelixizumab administered within 90 days of the initial diagnosis preserved the function of insulin-producing beta cells in the pancreas, as measured by C-peptide. No new or unexpected treatment-related safety concerns were raised by the trial.

GSK said it will continue to explore additional dosing regimens in order to help make a decision about the future of the otelixizumab development programme. In the meantime, an ongoing phase III study called DEFEND-2, which has a design similar to DEFEND-1, has been suspended.

"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.

The drug, which targets CD3, a T lymphocyte receptor involved in normal cell signalling, was licensed from Tolerx by GSK in a 2007 deal. The agreement covers the development and commercialisation of otelixizumab for a range of autoimmune and immune-mediated inflammatory diseases.

Tolerx has responsibility for clinical and regulatory activities for otelixizumab in type 1 diabetes in the US and retains an option to co-promote the product in type 1 diabetes in the US. GSK has exclusive rights to develop and commercialise otelixizumab in all other indications in the rest of the world and to develop the paediatric indication for type 1 diabetes in the US.