A phase III study of the anti-CD3 drug oteliximab in 240 newly diagnosed type 1 diabetes patients also produced negative findings. The dose – one-sixteenth of that used in previous trials – had been chosen to reduce adverse events seen previously, particularly Epstein-Barr virus activation. The low dose was not effective in preserving C-peptide. This study, dubbed DEFEND, was funded by Tolerx, with support from the Juvenile Diabetes Research Foundation.
"This is clearly an important pathway. Further studies will try to increase that dosage to duplicate the previous efficacy with fewer side effects," said Dr. Peter Gottlieb, professor of medicine and pediatrics at the University of Colorado, Denver.
Another compound under study, DiaPep277, was developed with the goal of preventing beta-cell destruction. Created by the removal of 24 of 500 amino acids from a "heat shock" protein involved in beta-cell destruction via T-cell activation, DiaPep277 had been shown to change destructive T cells into cytokine-secreting protective T-cells in mouse models of type 1 diabetes.
In one phase II study, injections of DiaPep277 in 100 newly diagnosed patients with type 1 diabetes preserved beta-cell insulin secretion for up to 2 years following diagnosis, said Dr. Itamar Raz, professor of medicine and director of the Hadassah Diabetic Center in Jerusalem, Hadassah Hebrew University Hospital.
DiaPep277 is currently in two phase III trials in which beta-cell function, insulin use, and glucose control are being monitored as key outcomes in more than 450 patients per trial. Results for one of the studies are expected by early next year, Dr. Raz said.
Dr. Skyler is an advisory panel and/or board member for a long list of companies that make diabetes-related products. He holds stock in and/or is a shareholder of Amylin Pharmaceuticals, Circulat Biotech, Dexcom, Ideal Life, Inspire Pharmaceuticals, Moerae Matrix, and Tandem Diabetes Care.
Dr. Gitelman and Dr. Sherry stated that they have no disclosures. Dr. Orban serves on the data safety monitoring board for Osiris Therapeutics and is a founding member of Orban Biotechs LLC. Dr. Gottlieb receives research funding from Tolerx, GlaxoSmithKline, MacroGenics, and Diamyd. He has consulted for Eli Lilly, Sanofi-Aventis, and Genentech.
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