Teplizumab shows hopes of moderating the pathophysiology behind type 1 diabetes….
Previous studies have shown that a single course of the anti-CD3 monoclonal antibody drug Teplizumab, given soon after diagnosis, improved beta cell responses for a year, but the responses waned after that. In new phase 2 trials, the team sought to determine whether two courses of the drug, one year apart, would have a better response. Teplizumab uses an antibody that is targeted against a molecule called CD3 in order to bind to the immune system’s T-cells. The drug then prevents the T-cells from attacking the beta cells of the pancreas.
Lead investigator Kevan Herold, MD, PhD, professor of immunobiology at Yale School of Medicine, director of the Yale Autoimmunity Center of Excellence, and deputy director for translational science at the Yale Center for Clinical Investigation, and colleagues conducted randomized, controlled trials and treated 52 patients with teplizumab for two weeks after diagnosis. A second course of the drug was administered after one year. Most of the patients in the treatment group were younger than 14 years old and had been diagnosed with new-onset type 1 diabetes within eight weeks of the trial’s start.
The study showed significant reduction in the loss of beta cells after two years with the treatment arm of the trial averaging 75% higher than the control group. "There’s a sub-group of people, 45%, that had a terrific response to the drug. In these patients, there was a three-fold improvement in their insulin responses compared to untreated participants," said Herold. "After two years, they’d lost less than 10 percent of their beta cell responses."
Because participants received daily insulin injections before and throughout the trial, researchers determined beta cell response by monitoring blood levels of C-peptide, a molecule that is produced at the same rate as endogenous insulin.
"Responders tended to be those who needed less insulin when they first got into trial, and had better control of their blood sugar levels," Herold said.
The team hopes to start on phase 3 trials soon which could lead to FDA approval of teplizumab. Herold said that, if approved, "this would be the first drug to change the natural course of type 1 diabetes since insulin."
Evan C Herold, et al., "Teplizumab (anti-CD3 mAb) treatment preserves C-peptide responses in patients with new-onset type 1 diabetes in a randomized controlled trial: Metabolic and immunologic features at baseline identify a subgroup of responders," Diabetes, 2013; doi: 10.2337/db13-0345