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Home»Pipeline»Teplizumab (CD3)

Teplizumab (Anti-CD3)

Teplizumab, also called MGA031 and hOKT3-gamma1 (Ala-Ala), is a humanized, anti-CD3 monoclonal antibody. Teplizumab binds to an epitope of the CD3-epsilon chain expressed on mature T lymphocytes and, by doing so, may modulate the pathological immunologic responses underlying multiple autoimmune diseases. Specifically, teplizumab may inhibit unwanted effector T cells and enhance beneficial regulatory T cell functions, thus promoting immune tolerance. MacroGenics retains full worldwide rights to teplizumab.

About Type 1 Diabetes

Type 1 diabetes (T1D) 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 T1D 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 T1D 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 June 2011, MacroGenics announced the publication in The Lancet of results from Protégé, a Phase 3 clinical study of teplizumab in T1D. The primary clinical endpoint was not met.  However, exploratory, post-hoc analyses suggest that teplizumab, an anti-CD3 monoclonal  antibody, when used in a full dose regimen, may preserve C-peptide and increase the percentage of patients requiring very low doses of insulin compared to those on placebo. In addition, these analyses identified certain subpopulations to be studied in future clinical trials.

The peer-reviewed article appearing in The Lancet
provides the results of per protocol as well as exploratory, post hoc analyses.  The findings suggest that “future studies of immunotherapeutic intervention with teplizumab might have increased success in prevention of a decline in beta-cell function (measured by C-peptide) and provision of glycaemic control at reduced doses of insulin if they target patients early after diagnosis of diabetes and children.”

Dr. Nicole Sherry (Massachusetts General Hospital) discussed her presentation of the Protégé study findings and exploratory, post hoc analyses at the American Diabetes Association 71st Scientific Sessions in San Diego on June 28, 2011.  Learn more: Dr. Sherry's video conference

Protégé and Protégé Encore Trials

Protégé is a two-year, randomized, double-blind, placebo-controlled clinical trial, with 513 patients aged 8 - 35, recently diagnosed with T1D, who were enrolled and treated at 83 clinical centers in North America, Europe, Israel, and India.  Protégé is ongoing and will complete a two year follow-up of patients.  Learn more: Protégé overview

The Protégé Encore trial was initiated in June 2009.  Protégé Encore is a Phase 3 global study of teplizumab in individuals with recent-onset T1D, which is designed to capture patient-reported outcome measures in addition to safety and efficacy data.  Dosing in the trial was suspended in October 2010; however, patients enrolled in the trial are being followed up for a period of time.  Learn more: Protégé Encore overview

Investigator-Sponsored Clinical Trials

In addition to the Protégé and Protégé Encore clinical trials, the following investigator-led clinical trials with teplizumab are being conducted:
  • The At Risk study is sponsored by TrialNet and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).  This study is designed to evaluate whether  teplizumab can help to prevent or delay the onset of T1D in relatives determined to be at very high risk for developing the disease.  Learn more: At Risk study
  • The AbATE Trial is a Phase 2 clinical trial in recent-onset T1D coordinated by the Immune Tolerance Network (ITN). In June 2011, data from the AbATE study was presented at the American Diabetes Association conference.  Learn more: AbATE study
  • The Delay Trial is a NIDDK-sponsored Phase 2 clinical trial in recent, but not recent-onset, T1D led by Dr. Kevan C. Herold of Yale University. 
    Learn more: Delay study