Presentations at ASN Kidney Week 2019 Highlight Breadth of ChemoCentryx Platform in Treatment of Complement 3 Glomerulopathy (C3G) and Focal Segmental Glomerulosclerosis (FSGS)
-- Highlights Study Design, Outcome Measures, and Baseline Patient Data in the Ongoing Avacopan ACCOLADE Phase II Trial in C3G
-- Reinforces Therapeutic Potential of Chemokine Receptor 2 (CCR2) Inhibition in the Treatment of FSGS --
Focal Segmental Glomerulosclerosis (FSGS) is a rare disease that attacks the kidney's filtering units (glomeruli), causing serious scarring which leads to permanent kidney damage and even failure. Treatment failure is common with the current standard of care, and FSGS is causal in at least 4 percent of patients with end-stage renal disease (ESRD).
Evidence to date support the role of CCR2 in chronic kidney disease (CKD), including FSGS, with recent studies showing that a CCR2 antagonist improved renal structure and reduced proteinuria in the murine models of FSGS. This study examined the effects of a CCR2 antagonist on podocyte integrity.
The presentation will highlight how treatment with a CCR2 antagonist provides rapid renal protection in the murine model of FSGS, as measured by improved proteinuria and renal structure, and a CCR2 blockade protected podocyte integrity. These findings are further evidence that specific inhibition of CCR2 has therapeutic potential in the treatment of FSGS and CCR2 antagonism represents a novel and mechanistically distinct approach for the treatment of FSGS.
Rapid benefits to proteinuria and renal structure are seen with inhibition of CCR2 in models of diabetic nephropathy (DN) and FSGS, and in a human DN trial; however the mechanism of CCR2 inhibition in renal protection is unclear. This study sought to evaluate a variety of methods to characterize CCR2 expression on renal progenitor cells in Bowman's capsule, and on activated parietal epithelial cells, which play a role in glomerulosclerosis.
This presentation will highlight the first report of the presence of CCR2 on non-hematopoietic renal parenchymal cells. The non-canonical CCR2+ cells are positive for CD133, CD24, and CD44 consistent with their being renal progenitor cells and activated PECs. These populations are markedly upregulated during kidney injury. These cells may be the targets of the CCR2 inhibitors that have been shown to be efficacious in murine models of CKD, as well as in human DN patients. CCR2 antagonism represents a novel approach for the treatment of CKD, including FSGS, and these studies are an important step in understanding the mechanism of their therapeutic benefit.
This informational poster will highlight the study design, outcome measures, and baseline patient data for the LUMINA-1 trial, which will provide data on the potential safety and efficacy of CCX140 in reducing proteinuria and improving renal function in FSGS patients.
There is currently no approved treatment for Complement 3 Glomerulopathy (C3G), a rare kidney disease characterized by variable degrees of proteinuria, hematuria, renal insufficiency and hypertension. Excessive activity of the alternative complement pathway is a hallmark of the disease.
Avacopan, an orally administered C5a receptor antagonist, has shown benefit in human trials of the complement-driven pathology in ANCA vasculitis and in pharmacological models of glomerulopathy associated with Factor H deficiency.
This informational poster will highlight the study design, outcome measures, and baseline patient data for ChemoCentryx’s ACCOLADE trial in C3G, one of the largest randomized controlled trials in this disease, ACCOLADE will measure the effects of 26 and 52 weeks of treatment with avacopan on the C3G Histologic Index, as assessed by renal biopsy and on reduction in proteinuria as measured by UPCR as compared to placebo.
ChemoCentryx is a biopharmaceutical company developing new medications targeted at inflammatory and autoimmune diseases and cancer. ChemoCentryx targets the chemokine and chemoattractant systems to discover, develop and commercialize orally-administered therapies. ChemoCentryx is currently focusing on its late stage drug candidates for patients with rare diseases, avacopan (CCX168) and CCX140.
Avacopan is an orally-administered small molecule that is a selective inhibitor of the complement C5a receptor, or C5aR. Avacopan is in Phase III development for the treatment of anti-neutrophil cytoplasmic auto-antibody-associated vasculitis (ANCA-associated Vasculitis). In clinical studies to date, avacopan was shown to be safe, well tolerated and provided effective control of the disease while allowing elimination of high-dose steroids, part of the current standard of care. ChemoCentryx is also developing avacopan for the treatment of patients with C3 glomerulopathy (C3G) and hidradenitis suppurativa (HS). The U.S. Food and Drug Administration has granted avacopan orphan-drug designation for ANCA-associated Vasculitis, C3G and atypical hemolytic uremic syndrome (aHUS). The European Commission has granted orphan medicinal product designation for avacopan for the treatment of two forms of ANCA-associated Vasculitis: microscopic polyangiitis and granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis), as well as for C3G. Avacopan was also granted access to the European Medicines Agency's (EMA) PRIority MEdicines (PRIME) initiative, which supports accelerated assessment of investigational therapies addressing unmet medical need.
The Company's other late stage drug candidate is CCX140, an inhibitor of the chemokine receptor known as CCR2, which is currently being developed for patients with focal segmental glomerulosclerosis (FSGS), a debilitating kidney disease. The U.S. Food and Drug Administration has granted CCX140 orphan-drug designation for the treatment of FSGS.
ChemoCentryx also has early stage drug candidates that target chemoattractant receptors in other Inflammatory and autoimmune diseases and in cancer.
ChemoCentryx cautions that statements included in this press release that are not a description of historical facts are forward-looking statements. Words such as "may," "could," "will," "would," "should," "expect," "plan," "anticipate," "believe," "estimate," "intend," "predict," "seek," "contemplate," "potential," "continue" or "project" or the negative of these terms or other comparable terminology are intended to identify forward-looking statements. These statements include the Company's statements regarding the achievement of anticipated goals and milestones, when clinical data might become available or be released, whether avacopan and CCX140 will be commercialized, and whether the Company's drug candidates will be shown to be effective in ongoing or future clinical trials. The inclusion of forward-looking statements should not be regarded as a representation by ChemoCentryx that any of its plans will be achieved. Actual results may differ from those set forth in this release due to the risks and uncertainties inherent in the
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Source: ChemoCentryx, Inc.