Trial Updates: The DEFEND Monoclonal Antibody and DIAMYD
As mentioned in a previous blog, George Washington and Georgetown Universities are partnering with the DEFEND 2 Monoclonal Antibody trials. (The Department of Endocrinology and Diabetes at Children's National Medical Center has just become involved in the DEFEND 2 trial with The George Washington University School of Medicine and Health Sciences by enrolling its first patient.) The DEFEND-2 Phase 3 trial employs humanized anti-CD3 monoclonal antibody (Otelixzumab).
"The DEFEND-1 study was a randomized, placebo controlled phase 3 study of 272 patients, age 12 to 45, with new-onset type 1 diabetes. DEFEND-1 was conducted at more than 100 study centers throughout North America and Europe. The study evaluates whether a single 8-day intravenous course of otelixizumab (3.1mg), administered not more than 90 days after the initial diagnosis of autoimmune type 1 diabetes, preserved the function of insulin-producing beta cells in the pancreas, as measured by C-peptide. Measurement of C-peptide (a protein that shows how much insulin the body is producing) at 12 months after dosing was the primary endpoint in DEFEND-1 and is a well established surrogate measure of beta cell function and a recommended endpoint by the U.S. Food and Drug Administration and the American Diabetes Association." (source-Tolerx Inc. literature)
Although the informational materials as supplied by Tolerx, Inc. (the above company that manufactures the trial drug), indicated that the structure of otelixizumab was different from other anti-CD3 monoclonal antibodies, including Macrogenics' teplizumab, it was revealed on March 11, 2011, that the Phase 3 DEFEND-1 study of otelixizumab, did not meet the primary efficacy endpoint of change in C-peptide at month 12 in patients with new-onset autoimmune type 1 diabetes. After review of the data, there was no new or unexpected treatment related safety concerns the presented during the DEFEND-1 study. New recruitment and dosing in the DEFEND-2 Study, the ongoing confirmatory Phase 3 study with a similar design as DEFEND-1 (the present study with which we are collaborators) has been suspended, pending further review of the DEFEND-1 results. Obviously, the lack of efficacy of these monoclonal antibody trials in terms of c-peptide is a great disappointment to the type 1 diabetes community.
There is some promising news in another type 1 diabetes research trial. The Diamyd trial (GAD-65 vaccine) conducted in our area at The University of Maryland also has been in the news recently (Diabetes in Control, Medication, Type 1 diabetes, issue 564, 3.8.11). It is to be noted that the EU Diamyd Phase III clinical study has completed the main 15-month visit, thus reaching an important milestone. The goal of the global phase three trial is to investigate if Diamyd can stop or slow pancreatic beta cell destruction, thus preserving beta cell production of insulin and the ability to control blood sugars. Of note, Diamyd has demonstrated the ability to slow the loss of beta cell function as compared to placebo in Phase 2 trials.
The EU Phase III trial is a multinational, multicenter, double-blind, randomized, placebo-controlled trial that enrolled 320 patients between 10 to 20 years of age with the diagnosis of type one diabetes within 3 months. 33 percent of patients received four injections with Diamyd, 33 percent received two injections with Diamyd, followed by two injections with placebo, and 33 percent received four injections with placebo. The injections were given on day one, one month, three months and nine months. The next step will be followed by compilation and analysis of data from 60 European clinics during the next few months; thereafter, the study will be "unblinded."
The Diamyd global phase III program in the United States (DiaPrevent) is fully enrolled as of December 2010. According to Diamyd Medical, it is hoped that the main aspect of the study will be completed during the spring of 2012. 640 recently diagnosed patients between 10 to 20 years have been enrolled in both the EU Phase 3 and the Diaprevent studies. (source-Diamyd Medical)
I will continue to keep you updated as more information becomes available.