Antibody May Help Lower Blood Sugar in Type 2 Diabetes Patients

An experimental antibody has been shown to lower blood sugar in type 2 diabetes patients with a single dose. These encouraging results have been indicated by early-stage trials. Xoma Ltd., a Berkeley, California based biotechnology company, has developed an injectable drug, known as XOMA 052, that could potentially improve blood sugar control in type 2 diabetes patients with as little as one dose per month. The antibody works by blocking interleukin-1 beta (IL-1 beta), a protein that causes inflammation-linked to damage of insulin-producing cells called islet cells. Two Phase 1 trials of 48 patients with five dose groups in a US study and three dose groups in a European study, resulted in a single injection of the antibody reducing levels of HbA1c (a standard measure of glucose control) in four of five tested dose levels when compared to placebo. In addition, average HbA1c levels were reduced in all 5 groups with reductions of as much as 0.6 percent after 28 days when compared to the baseline. In a telephone interview, Alan Solinger, vice president of clinical immunology at Xoma stated, “This could be a disease-modifying drug that allows the pancreas to get back to a more normal state.” He also added, “With one dose we have a 0.6 percent improvement. If you extrapolate to three months, the improvement is probably going to be even better.” According to Xoma, the trials also showed that XOMA 052 improved C-reactive protein levels as well as other diabetes and inflammation markers. The trials showed no evidence of serious adverse side effects or infusion reactions. Dr. Marc Donath, professor at the University Hospital of Zurich and lead investigator of Xoma's European trial, said in a statement, “If, as we hypothesize, the inhibition of IL-1 beta improves the condition of insulin-producing cells in diabetes patients by targeting inflammation, the implications would be very encouraging for the treatment of the disease.” Donath said that XOMA 052 is the first anti-IL-1 beta specific drug to demonstrate biological activity against diabetes and inflammation in Type 2 diabetes patients and that since HbA1c reflects average blood glucose over a three-month period, the trial levels of early reduction are particularly encouraging. Xoma’s chief executive, Steven Engle, said, “It is very exciting to see that a single dose of XOMA 052 had such positive biological activity and duration of effect, and was well tolerated.” He explained that the results exceeded expectations for a Phase I study and acknowledged that even though the numbers of patients were limited and more studies are needed, “The potency demonstrated to date is compelling.” Engle also noted “We are encouraged not only to proceed with additional studies in diabetes but also to expand our clinical development of XOMA 052 in other indications such as rheumatoid arthritis, acute gout and systemic juvenile idiopathic arthritis.” Xoma plans to initiate mid-stage clinical trials of XOMA 052 later this year. The trials were presented in Rome at a meeting of the European Association for the Study of Diabetes.