Teplizumab (Anti-CD3)

Our lead product candidate, teplizumab (MGA031), is a humanized monoclonal antibody in late-stage clinical trials for the treatment of Type 1 Diabetes, an autoimmune disease for which there has not been a treatment approved since the 1920s (i.e., insulin).

About Type 1 Diabetes

Type 1 diabetes is an autoimmune disease in which the body's immune system attacks and destroys the insulin-producing beta cells of the pancreas. The symptoms associated with type 1 diabetes can appear suddenly and leave a person dependent on injected insulin for life. The disease carries the constant threat of devastating complications such as heart and kidney disease, nerve damage and blindness. Although diagnosis most often occurs in childhood and adolescence, the disease can strike adults as well. Individuals with type 1 diabetes must test their blood sugar four or more times per day and take multiple insulin injections daily or continually infuse insulin through a pump. While trying to balance insulin doses with their food intake and daily activities, people with this form of diabetes must always be prepared for serious hypoglycemic (low blood sugar) and hyperglycemic (high blood sugar) reactions, both of which impact quality of life and can be life threatening. This balance is especially difficult to achieve in children and young adults who are very active physically.

About Teplizumab

Teplizumab, also known as hOKT3γ1(Ala-Ala), has been engineered to alter the function of the T lymphocytes that mediate the destruction of the insulin-producing beta cells of the islets of the pancreas. Teplizumab binds to an epitope of the CD3-epsilon chain expressed on mature T cells and by doing so, may modulate the immunologic response that is a key component of the disease. If teplizumab is effective and has the ability to preserve or protect beta cells of the pancreas, patients may require less injected insulin and their blood glucose levels may be easier to control. Teplizumab represents a paradigm shift in the management of autoimmune disease that focuses on the induction of tolerance rather than broad spectrum immunosuppression.

In Phase 2 trials of teplizumab, a single brief course of teplizumab delivered within the first six weeks following diagnosis was shown to improve c-peptide responses, reduce HbA1c levels and reduce insulin requirements for at least two years. This translated into better metabolic control for the treated individuals for the two-year duration of the study. These findings are being further studied in the Protégé and Protégé Encore clinical trials, described below.

 Protégé and Protégé Encore Trials

In June 2009, MacroGenics and its partner, Eli Lilly & Company, announced that Protégé, their pivotal Phase 2/3 clinical study evaluating teplizumab in individuals with recent-onset type 1 diabetes, had achieved its targeted patient enrollment. The Protégé trial is a randomized, double-blind, multi-center, multi-national, 4-arm, controlled study designed to evaluate the safety and efficacy of teplizumab in individuals with recent-onset type 1 diabetes, aged 8 to 35, who are within 12 weeks of their diagnosis. More than 530 individuals are enrolled in the study across 14 countries, including the United States. The primary composite endpoint for Protégé includes both the patient's total daily insulin usage and his/her HbA1c levels at 12 months. Secondary endpoints are evaluated at 24 months. Longer term safety and efficacy data from patients who complete the Protégé trial are being collected in a separate Phase 3 study called the Protégé Extension trial.

The companies also announced in June 2009 that they had initiated the Protégé Encore trial, a Phase 3 global study of teplizumab in individuals with recent-onset type 1 diabetes, which is designed to capture patient-reported outcome measures in addition to safety and efficacy data. Learn more: Protégé Studies

• The AbATE Trial is a Phase 2 clinical trial in recent-onset type 1 diabetes coordinated by the Immune Tolerance Network (ITN). In March 2009, ITN announced that it had completed enrolling the full cohort of 83 patients in the AbATE trial.  Learn more: AbATE study
• The Delay Trial is a National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) sponsored Phase 2 clinical trial in recent, but not recent-onset, type 1 diabetes led by Dr. Kevan C. Herold of Yale University. 
  Learn more: NIDDK study
• Prior research indicates that reprogramming an islet cell transplant recipient's immune system may be important to prevent the recurrence of an autoimmune attack on the transplanted islets. Previous studies of teplizumab have supported the view that prolonged transplant tolerance may be possible. Ongoing clinical trials in this area include a Phase 2 clinical trial sponsored by NIH and led by Dr. Bernhard Hering of the University of Minnesota. 
  Learn more: Islet Transplantation study

 
Eli Lilly and Company Relationship

In October 2007, MacroGenics and Eli Lilly entered into a global strategic alliance to develop and commercialize teplizumab as well as other potential next generation anti-CD3 molecules for use in the treatment of autoimmune diseases. As part of the deal, Lilly acquired the exclusive rights to teplizumab. Learn more