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 trials as well as the lessons that have been learned from the clinical trials involving selection of end points and the inclusion of diverse study populations. EXPERT OPINION: Teplizumab has been shown to preserve β cell function in patients; however, it does not represent a 'cure' for patients, and its efficacy does entail a significant advance in arresting the progression of the disease toward complete insulin deficiency and reliance on exogenous insulin.