Xoma Ltd, a leader in the discovery and development of therapeutic antibodies, announced the expansion of its development strategy for its Xoma 052 antibody to interleukin-1 beta (IL-1 beta) to include effects on cholesterol lowering, reducing plaque deposits and damage to heart muscle and resulting long-term effects that can lead to heart attack, stroke and congestive heart failure. The strategy is supported by results from Xoma 052 phase-1 trials demonstrating improvement in biomarkers associated with cardiovascular risk, ongoing clinical trials in cardiovascular disease with other IL-1 targeted agents, animal studies with Xoma 052 that have demonstrated significant reductions in plaque formation and improvements in lipid levels, and positive results with another IL-1 targeted agent in an animal model of cardiac remodeling after heart attack. Xoma's current Xoma 052 programme is focused on Type 2 diabetes and this expansion represents an enormous increase in the number of patients who could be helped by this general anti-inflammatory approach.
In Xoma's phase-1 Xoma 052 trials, patients with Type 2 diabetes had improvements in high-sensitivity C-reactive protein (hsCRP) and erythrocyte sedimentation rate (ESR), biomarkers of systemic inflammation associated with cardiovascular risk as well improvement in diabetic parameters. Two ongoing clinical trials of anakinra, another agent targeting IL-1, in acute coronary syndromes provide further support for a new anti-inflammatory approach to cardiovascular disease. Recently reported preclinical animal results have demonstrated that Xoma 052 treatment resulted in reduction in the formation of atherosclerotic plaque. Other recent preclinical animal results with Xoma 052 have shown reductions in total cholesterol without reduction in high density lipoprotein, and reduction in triglycerides and free fatty acids. Recently published results demonstrated that treatment with anakinra in a mouse model of heart attack resulted in amelioration of the adverse cardiac remodeling, and a statistically significant improvement in survival compared to control animals.
"Xoma 052 results demonstrating improved cardiovascular biomarkers in our phase-1 trials and significant improvements in plaque formation and dyslipidemia in established mouse models, together with the growing recognition of systemic inflammation as a cardiovascular risk factor as recently demonstrated in the Jupiter study, support an expanded strategy for the development of Xoma 052 in cardiovascular diseases," said Patrick J Scannon, Xoma's executive vice president and chief medical officer.
"Despite many recent advances in prevention and treatment, cardiovascular disease remains the leading cause of death in the United States, demonstrating the ongoing need for new therapies," said Steven B Engle, Xoma's chairman and chief executive officer. "While we remain focused on developing Xoma 052 in Type 2 diabetes, we believe expanding our development strategy to include cardiovascular diseases, to be implemented as resources permit, will lay the groundwork to dramatically expand the potential for this product candidate."
Inflammation is a critical component of many diseases and IL-1 has been demonstrated to be one of the key cytokines involved in the pro-inflammatory process. At normal physiological levels, IL-1 is an important part of the host defense system. In elevated amounts, IL-1 has been demonstrated to have a pathologic role in initiating, maintaining or exacerbating inflammatory conditions including Type 2 diabetes, cardiovascular disease, rheumatoid arthritis, gout and other diseases.
Xoma 052 is potent antibody with the potential to improve the treatment of patients with a wide variety of inflammatory diseases.
Xoma discovers, develops and manufactures novel antibody therapeutics for its own proprietary pipeline as well as through license and collaborative agreements with pharmaceutical and biotechnology companies, and under its contracts with the US government.