Macrogenics' Protege Phase 3 clinical study of teplizumab in type 1 diabetes published in The Lancet

MacroGenics, Inc., a privately held biotechnology company that develops immunotherapeutics to treat autoimmune disorders, cancer and infectious diseases, announced the publication in The Lancet of results from Protege, a Phase 3 clinical study of teplizumab in type 1 diabetes.  Exploratory, post-hoc analyses suggest that teplizumab, an anti-CD3 monoclonal antibody, when used in a 14-day full dose regimen, preserves C-peptide and increases the percentage of patients requiring very low doses of insulin (< 0.25 U/kg/day) with good glycemic control (glycosylated hemoglobin, or HbA1C < 7%) compared to placebo.  In addition, these analyses revealed that certain subpopulations may be more likely to respond to teplizumab treatment.  These findings also were presented today by Dr. Nicole Sherry (Massachusetts General Hospital for Children) at the annual American Diabetes Association meeting.

Protege is a two-year, randomized, double-blind, placebo-controlled clinical trial, with 513 patients aged 8–35, recently diagnosed with type 1 diabetes, who were enrolled and treated at 83 clinical centers in North America, Europe, Israel, and India. Participants were allocated 2:1:1:1 to receive daily infusions of teplizumab (full dose for 14 days, 1/3 dose for 14 days, or full dose for 6 days) or placebo at baseline and at 6 months. The primary composite endpoint of the Protege study was the percentage of patients with insulin use < 0.5 U/kg/day and HbA1C < 6.5% at 1 year.  Although teplizumab was shown to have an acceptable safety profile, the primary endpoint was not achieved, as had been previously announced in a joint communication with Eli Lilly and Company in October 2010.  Protege is ongoing and will complete the 2-year follow-up in 2011.

The peer-reviewed article appearing in The Lancet is titled, "Teplizumab for treatment of type 1 diabetes (Protege study): 1-year results from a randomized, placebo-controlled trial," by Sherry, et al. and 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."

The article indicates that teplizumab treatment may preserve beta cell function as measured by C-peptide, allowing less insulin use to achieve the same glycemic control as patients receiving placebo. A greater proportion of patients in the teplizumab groups were able to discontinue or use very low doses of insulin compared to the placebo group.  A reduced insulin requirement while maintaining glycemic control appears to support teplizumab having a biological effect.

In the safety analyses, the proportion of patients who had adverse events and serious adverse events was similar across the four study groups.  Rash was the most common clinical adverse event reported more frequently with teplizumab than placebo. Mild cytokine release syndrome was infrequent but greater in treatment groups compared to placebo. The safety profile was characterized by transient increases in some liver function test results and transient decreases in white cells that prevent infections. However, no increase in overall infections was seen.

"We are very pleased to have teplizumab Phase 3 data published in this prestigious journal," stated Dr. Scott Koenig, President and CEO of MacroGenics.  "Although the Protege study missed its primary endpoint, the data appear to indicate that teplizumab has a desired biological effect in certain subpopulations with a potentially meaningful therapeutic benefit for patients with recent-onset type 1 diabetes.  These groups include patients for whom treatment is begun less than or equal to 6 weeks after diagnosis and in children 8 -11 years old.  In the coming months, MacroGenics will be exploring possible pathways forward for continued development of teplizumab."