Low doses of the GlaxoSmithKline drug otelixizumab did not preserve the function of the insulin-producing beta cells of the pancreas in those newly diagnosed with type 1 diabetes, according to recent research.
The results of the phase 3 trial – called the Durable Response Therapy Evaluation for Early or New-Onset Type 1 Diabetes, or DEFEND-1 – sends researchers back to the drawing board in an attempt to use otelixizumab, an antibody created specifically to treat type 1 diabetes and other autoimmune diseases, to help maintain insulin function.
While the research was published last month in the American Diabetes Association journal Diabetes Care, GSK researchers learned in 2011 that the low-dose trial failed to meet the desired outcome during early analysis, though it proved safer than the higher dose used in the phase 2 trial.
“We felt that it was important to share and publish the information, because this is such an important area for study, and we feel there will be immune modulator therapies found in the future that are effective. However, at this dose otelixizumab was not effective,” said lead author Dr. Ronnie Aronson of LMC Diabetes & Endocrinology, Toronto, Ontario, Canada, in an interview with Medscape Medical News.
According to Aronson, otelixizumab was one of three antibodies designed exclusively to regulate the T cells that impact the pancreas, reducing those that attack beta cells while boosting those that protect beta cells. The others are teplizumab and rituximab.
While otelixizumab did show success at higher levels, increasing beta-cell function by as much as 80 percent after 30 months, according to researchers at the Belgian Diabetes Registry, side effects including the reactivation of latent Epstein-Barr virus – a member of the herpes family associated with mononucleosis and a host of other immune disorders – led to the study of lower doses of the drug.
Additional studies to determine if other doses of the drug will be effective for new-onset type 1 patients are currently underway, according to Melinda Stubbee, director of GSL Global External Communications in Research Triangle Park, North Carolina.
“Further dose-ranging studies should be undertaken to effectively determine a viable therapeutic window with proven efficacy and a tolerable safety profile,” researchers said.