In December 2016, we expanded our existing kidney health alliance with Vifor Pharma to include the development and commercialization of CCX140 for renal diseases. The alliance will initially focus on the joint development of CCX140 in rare kidney diseases, with Vifor Pharma retaining an option to solely develop and commercialize CCX140 in more prevalent forms of chronic kidney disease (CKD). Under the agreement, ChemoCentryx retains marketing rights for rare renal disease in the U.S. and China, while Vifor Pharma has commercialization rights in the rest of the world.
In May 2020, we announced topline data from a forty-six (46) patient Phase II dose-ranging trial in the orphan kidney disorder, primary Focal Segmental Glomerulosclerosis (FSGS). The LUMINA-1 trial tested CCX140, an orally-administered selective inhibitor of the chemokine receptor known as CCR2, in primary FSGS subjects. In the study, CCX140 did not demonstrate a meaningful reduction in proteinuria relative to the control group after 12 weeks of blinded treatment.
ChemoCentryx does not plan to further develop CCX140 in patients with FSGS but anticipates topline data from its LUMINA-2 trial by the end of 2020.
The chemokine receptor known as CCR2 has been identified as a main driver of inflammatory monocyte and macrophage recruitment into diseased kidneys. Various cell types in glomeruli also appear to express CCR2, which drives some of the renal impairment in diabetic nephropathy. Levels of MCP-1 (also known as CCL2), the main ligand for CCR2, are elevated in the kidneys of patients with diabetic nephropathy. MCP-1 is produced by kidney cells in response to such factors as high blood glucose levels and physical stresses. As a result, levels of MCP-1 in the urine are strong indicators of renal damage and correlate well with albuminuria and interstitial macrophage numbers.
In preclinical studies conducted by ChemoCentryx and other independent researchers, CCR2 inhibition leads to pronounced reduction in albuminuria, as well as improvement in markers of renal function such as serum creatinine and blood urea nitrogen (BUN). CCX140 has been shown to be a potent and selective inhibitor of CCR2, which is required for monocytes to infiltrate the kidney, where they differentiate into macrophages. Preclinical model data suggest that once these damage-promoting cells are inhibited, the kidney is thought to be able to function in a healthier state, and perhaps even restore certain renal function.
Efficacy in Diabetic Nephropathy in a Phase II Clinical Trial of Chemokine Receptor 2 Inhibitor CCX140-B, Richard J. Glassock, Elena Henkel, Heidrun Mehling, Christoph Hasslacher, Ioanna Gouni-Berthold, Vladimir Tesar, Antonia Potarca, Pirow Bekker, Thomas J. Schall. Presented at the American Society of Nephrology Annual Kidney Week Meeting, 2015.
The effect of CCR2 inhibitor CCX140-B on residual albuminuria in patients with type 2 diabetes and nephropathy: a randomised trial Dick de Zeeuw, Pirow Bekker, Elena Henkel, Christopher Hasslacher, Ioanna Gouni-Berthold, Heidrun Mehling, Antonia Potarca, Vladimir Tesar, Hiddo J Lambers Heerspink, Thomas J Schall, for the CCX140-B Diabetic Nephropathy Study Group. The Lancet Diabetes & Endocrinology, Published online August 10, 2015 http://dx.doi.org/10.1016/S2213-8587(15)00261-2
CCR2 inhibition: a panacea for diabetic kidney disease? Weir MR, The Lancet Diabetes & Endocrinology, published online August 10, 2015 http://dx.doi.org/10.1016/S2213-8587(15)00286-7
Hanefeld M, Schell E, Gouni-Berthold I, et al. Orally-administered chemokine receptor CCR2 antagonist CCX140-B in type 2 diabetes: a pilot double-blind, randomized clinical trial. J Diabetes Metab 2012; 3: 225. DOI:10.4172/2155-6156.1000225.
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CCR2 inhibition improves renal function in diabetic BKS db/db mice. Sullivan TJ, Miao Z, Zhao N, Berahovich R, Powers JP, Ertl L, Jaen JC, Schall TJ. 72nd American Diabetes Association Scientific Sessions, Philadelphia (PA); June 8-12, 2012. Abstract # 517-P.