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 I studies included 48 patients with type 2 diabetes from five dose groups in a US study and three dose groups in a European study. A total of 40 patients received Xoma 052 and eight received placebo. Patients were followed for two to three months.
Glucose control is said to be an important determinant in the health of diabetes patients. Glycosylated hemoglobin (HbA1c) is a standard measure of average glucose control over a three-month period. Although the number of patients in each dose group was limited, median HbA1c levels were reduced in all five groups and the reduction was as much as 0.6% at 28 days. A single dose of Xoma 052 reduced median HbA1c in four of five drug dose levels compared to placebo.
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.
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.
Steven Engle, Xoma’s chairman and CEO, said: “Although the numbers of patients were limited and more studies are needed, the potency demonstrated to date is compelling and 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.”