Teplizumab

Teplizumab (also known as PRV-031; formerly also known as MGA031 and hOKT3γ1(Ala-Ala)) is a humanized anti-CD3 monoclonal antibody that is being evaluated for treatment and prevention of type 1 diabetes mellitus (T1DM) by the biopharmaceutical company Provention Bio. Teplizumab has also been evaluated for treatment of renal allograft rejection, for induction therapy in islet transplant recipients, and for psoriatic arthritis. Teplizumab (also known as PRV-031; formerly also known as MGA031 and hOKT3γ1(Ala-Ala)) is a humanized anti-CD3 monoclonal antibody that is being evaluated for treatment and prevention of type 1 diabetes mellitus (T1DM) by the biopharmaceutical company Provention Bio. Teplizumab has also been evaluated for treatment of renal allograft rejection, for induction therapy in islet transplant recipients, and for psoriatic arthritis. The Fc region of this antibody has been engineered to have Fc receptor non-binding (FNB) properties. The mechanisms of action of teplizumab appear to involve weak agonistic activity on signaling via the T cell receptor-CD3 complex associated with the development of anergy, unresponsiveness, and/or apoptosis, particularly of unwanted activated Teff cells. In addition, regulatory cytokines are released and regulatory T cells are expanded that may lead to the reestablishment of immune tolerance This antibody has been used in clinical trials with the aim of protecting the remaining β-cells in newly diagnosed type 1 diabetes mellitus patients. Immunomodulatory agents such as anti-CD3-antibodies may restore normal glucose control if provided in very early stages of the disease, when there are still beta cells . Teplizumab was originally developed at Columbia University, and was then further developed at MacroGenics, Inc., including a collaboration with Eli Lilly to conduct the first Phase 3 clinical trial in early-onset type 1 diabetes. Provention Bio has announced plans to re-start Phase-3 development in T1DM after the initial Phase 3 trial conducted by Macrogenics failed to meet the primary endpoint yet revealed efficacy signals in C-peptide in the totality of the patients and in other endpoints in sub-populations now objects of the Provention Bio study