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| |  XOMA 052 Shows Promise in the Treatment of Type 2 Diabetes: Presented at IDF By Brian Hoyle MONTREAL -- October 23, 2009 -- XOMA 052, an engineered monoclonal antibody with a very high affinity for interleukin (IL)-1 beta, shows promise in the treatment of type 2 diabetes, with reductions in markers indicative of beta-cell dysfunction for up to 3 months following a single subcutaneous injection. “This is just a safety study, but so far so good,” said presenter Jeffrey Feldstein, MD, XOMA, LLC, Berkeley, California, on October 20 at the 20th World Diabetes Congress of the International Diabetes Federation (IDF). Previous studies have shown that XOMA 052 binds avidly to IL-1 beta, which is a pro-inflammatory cytokine involved in a number of diseases including diabetes. Antibody binding to IL-1 beta blocks activation of the IL-1 receptor, which in turn blocks signalling that stimulates inflammation. Beta cells from patients with type 2 diabetes are enhanced in expression of inflammatory markers including IL-1 beta, implicating IL-1 beta as a therapeutic target. The hope for XOMA 052 is that the modulation of IL-1 beta-mediated inflammation would lessen pancreatic beta-cell destruction and so maintain their insulin producing capacity. The randomised, blinded, placebo-controlled study involved the use the increasing doses of XOMA 052 in patients with type 2 diabetes whose disease was inadequately controlled. Inclusion criteria included glycosylated haemoglobin (Hb A1C) levels >=7.5% to <=12% and a body mass index >=23 kg/m2 and <=36 kg/m2. Exclusion criteria included the use of inhibitors of type 2 diabetes, glucagon-like peptide-1, dipeptidyl peptidase-4, and anti-inflammatories other than aspirin; fasting C peptide <1.2 mcg/L; and high sensitivity C-reactive protein (hsCRP) >30 mg/L. Separate groups of 5 participants received either a single subcutaneous dose of 0.03, 0.1, or 0.3 mg/kg XOMA 052, or 3 subcutaneous doses of 0.03 or 0.3 mg/kg of the antibody every other week. In each group, 1 participant received placebo. All participants were followed for 56 to 84 days. No adverse effects were apparent. During the 22 day half-life of the administered antibody, its mean bioavailability was consistently 60% (range 30%-90%). In participants who received a single dose, hs-CRP was reduced by a median of 52% (range 25%-79%) within 14 days, compared with a median increase of 8% for placebo. At 42 days, Hb A1C was changed by a median of -0.1% (range, -2.2% +- 0.7%) as compared with a median of +0.3% for placebo. Fasting plasma glucose was also decreased by the application of XOMA 052 (median of 10%; 20 mg/dL) at 42 days, compared with the median of 2% (7 mg/dL) for placebo. According to Dr. Feldstein, these results, combined with the previous findings of no serious adverse events including drug-related hypoglycaemia, neutropenia, or serious infection, and the absence of weight gain and an immune response upon administration of the antibody, supports a new therapeutic approach to cardiometabolic disease by targeting IL-1 mediated inflammation. “Our aim is that the antibody will be injected periodically, once every few months or so. My feeling is that this may one day even augment other treatments, but we don’t know enough about that yet,” said Dr. Feldstein. Funding for this study was provided by XOMA LLC. [Presentation title: XOMA 052, A Potential Disease-Modifying Anti-Interleukin-1 Beta
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