Teplizumab


Teplizumab is a humanized anti-CD3 monoclonal antibody that is being evaluated for treatment and prevention of type 1 diabetes mellitus 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 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 University of Chicago in partnership with Ortho Pharmaceuticals, 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. After the initial Phase 3 trial conducted by Macrogenics failed to meet the primary endpoint, the drug was acquired by Provention Bio, which restarted development based on subset analysis of the original trials.
A subsequent phase 2 study showed that teplizumab could delay the development of diabetes in family members of type I diabetics showing signs of progression towards diabetes by about two years after a single treatment, renewing interest in its use as a preventive rather than therapeutic treatment in high-risk patients.