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New research has shown that XOMA 52, an antibody drug can address the inflammation process which can lead to beta cell death and help to preserve them, plus it is only a once a month dose with little or no side effects.
Berkeley, California-based Xoma said interim results from two small Phase 1 trials involving 48 patients showed that a single injection of the antibody reduced levels of HbA1c — a standard measure of glucose control — in four of five tested dose levels compared to placebo.
XOMA 052 addresses inflammation as an underlying cause of diabetes by targeting Interleukin-1 beta (IL-1 beta), a master signaling protein which triggers inflammatory pathways in the body. This study is an important addition to the medical research indicating that decreasing inflammation may reduce disease progression in diabetes.
XOMA 052 demonstrated biological activity in patients with Type 2 diabetes as measured by diabetes and inflammatory markers. The interim analysis of two single-dose, dose-escalation, Phase 1 studies included 48 patients with Type 2 diabetes from five dose groups in a U.S. study and three dose groups in a European study. Forty patients received XOMA 052 and eight received placebo. Patients were followed for two to three months.
Although the number of patients in each dose group was limited, median HbA1c levels were reduced in all 5 groups and the reduction was as much as 0.6 percent at 28 days. A single dose of XOMA 052 reduced median HbA1c in 4 of 5 drug dose levels compared to placebo.
IThe body controls the amount of glucose in the bloodstream by causing the pancreatic islet cells to produce insulin. Healthy individuals will rapidly produce appropriate levels of insulin in response to large glucose increases while diabetes patients will not. In general, an increase over three months in the ability of islet cells to produce insulin is considered medically meaningful in patients with diabetes.
Tests of the body’s insulin producing capability were performed in the European study of XOMA 052 using the glucagon-arginine-glucose (GAG) stimulation test. The GAG stimulation test is a standard measure of the health of insulin-producing islet cells and mimics the real-life conditions of a meal with multiple dietary components to evaluate the response of islet cells in making insulin.
The GAG stimulation test was performed at a European academic diabetes research and treatment center where it is used routinely. For the interim analysis, data were available from the two lowest dose groups. A single dose of XOMA 052 increased insulin production at 28 and 91 days compared to baseline, while placebo-treated patients showed no improvement.
Ultrasensitive C-reactive protein (usCRP) is a standard measure of systemic inflammation associated with multiple diseases and an indicator of cardiac risk. At 28 days, a single dose of XOMA 052 reduced usCRP as compared to placebo in all of the dose groups. These results indicate the ability of a relatively small amount of drug to show anti-inflammatory activity. The safety and pharmacokinetic results showed that XOMA 052 was well tolerated at all five dose levels and had a potential dosing profile of once per month or longer in Type 2 diabetes patients. There was no evidence of drug-related serious adverse events or infusion reactions.
"XOMA 052 is the first anti-IL-1 beta specific drug to demonstrate biological activity against diabetes and inflammation in Type 2 diabetes patients," said Marc Y. Donath, M.D., a pioneer in anti-inflammatory approaches to Type 2 diabetes, Professor at the University Hospital of Zurich and European clinical trial principal investigator. "Bearing in mind that HbA1c reflects average blood glucose over a three month period, these levels of early reduction are particularly encouraging."
Dr. Donath continued, "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 promising for the treatment of the disease. This study suggests that XOMA 052 may address this fundamental and still largely unexplored inflammatory pathway and warrants continued clinical investigation."
Alan Solinger, M.D., XOMA’s Vice President of Clinical Immunology said, "Type 2 diabetes patients, their caregivers and advocates have long sought improved treatment options that go beyond glucose management and frequent insulin injections. Current approaches force more insulin out of ‘tired’ pancreatic beta cells or make peripheral cells more sensitive to insulin, whereas XOMA 052 targets inflammation — a newly recognized mechanism in Type 2 diabetes. Showing an increase in insulin production three months after a single infusion is remarkable. If these increases are confirmed in larger studies, we could have a disease-modifying therapy."
The oral presentation at the European Association for the Study of Diabetes (EASD), "XOMA 052, an Anti-IL-1 beta Antibody, in a Double-Blind, Placebo-Controlled, Dose Escalation Study of the Safety and Pharmacokinetics in Patients with Type 2 Diabetes Mellitus – A New Approach to Therapy,"