Treatment of new onset type 1 diabetes with teplizumab: successes and pitfalls in development

Introduction: Type 1 diabetes is an organ-specific autoimmune disease, characterized by selective destruction of insulin-producing pancreatic β-cells by T-cell-mediated inflammation. Beginning with studies of cyclosporin A in the 1980s, but with more activity in the past decade, there have been a number of clinical trials to test whether immunotherapies can arrest the decline in C-peptide, which is associated with progression of type 1 diabetes leading to the metabolic instability that characterizes the disease. One of the most promising agents, teplizumab, is an FcR-nonbinding anti-CD3 monoclonal antibody that has been tested in Phase II – III clinical trials and was shown to preserve the C-peptide levels and reduce the need for exogenous insulin. Areas covered: In this review, we discuss the recent update on clinical data obtained from trials of teplizumab in type 1 diabetes, the drug’s postulated mechanism of action and the identification of responders to therapy. We highlight the results of recent tri...