MOUNTAIN VIEW, Calif., June 2, 2014 (GLOBE NEWSWIRE) -- ChemoCentryx, Inc., (Nasdaq: CCXI ) reported today additional Phase II data related to CCX168, an orally administered inhibitor that targets the receptor for the complement protein known as C5a (C5aR). Data were presented in an oral presentation at the 51 st European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Congress, taking place from May 31-June 3 in Amsterdam.
Data from the first two steps of the CLEAR trial show that patients receiving CCX168 showed improvements in the Birmingham Vasculitis Activity Score (BVAS), an overall disease activity index, including efficacy observed in both the renal and the non-renal components of the BVAS. BVAS response at 12 weeks was higher in patients on CCX168 than those patients receiving the standard of care. BVAS remission (a higher threshold that is thought to require 24 weeks of treatment or longer for maximum effect) at 12 weeks was comparable to standard of care (see table below for details). Both non-renal and renal disease components of BVAS were improved in patients on CCX168 treatment. Additionally, as previously reported, patients treated with CCX168 as compared to standard of care showed greater improvements in renal function based on renal disease activity measurements including estimated glomerular filtration rate (eGFR), urinary albumin:creatinine ratio (ACR), and urinary monocyte chemoattractant protein-1 (MCP-1):creatinine ratio.
"Along with an improvement in the renal component of the BVAS index, these data show additional reductions in the non-renal component of BVAS in both groups of patients taking CCX168, as compared to standard of care. These results may indicate that our orally-active complement C5a receptor inhibitor CCX168 has potential broader utility beyond just the renal manifestation of ANCA-associated vasculitis," said Thomas J. Schall, Ph.D., President and Chief Executive Officer, ChemoCentryx. "We look forward to further evaluating the effect of CCX168 on overall disease activity, as well as on biomarkers, including urinary albumin, MCP-1 excretion and other complement, cytokine and chemokine markers, in the recently initiated step 3 of the ongoing CLEAR clinical trial."
The BVAS index is an important indicator of systemic health (since ANCA-associated Vasculitis is a systemic disease), and includes disease activity assessment in nine body systems: general health, cutaneous, mucous membranes/eyes, ears, nose and throat (ENT), chest, cardiovascular, abdominal, renal and nervous system. A reduction in BVAS score indicates disease improvement. In addition to significant overall reduction in mean BVAS scores reported earlier, these latest data show that patients taking CCX168 experienced meaningful improvements in both renal and non-renal disease aspects after 12 weeks of treatment (see table below).
| Mean (SEM) % Change in BVAS from Start of Study to Week 12 | CCX168 + Cyclophosphamide (CYC) + Low-Dose Steroids (N=8) | CCX168 + CYC + No Steroids (N=8) | Standard of Care: CYC + High-Dose Steroids (N=9) |
| BVAS Total | -71 +/- 9% | -65 +/- 11% | -26 +/- 25% |
| BVAS Renal | -64 +/- 10% | -50 +/- 15% | -16 +/- 26% |
| BVAS Non-renal | -81 +/- 33% | -83 +/- 29% | -15 +/- 6% |
| % of Patients BVAS Response * | 6 of 7 (86)% | 7 of 8 (88)% | 4 of 9 (44)% |
| % of Patients BVAS Remission ** | 2 of 7 (29)% | 2 of 8 (25)% | 3 of 9 (33)% |
*BVAS Response = BVAS score decrease of at least 50% and no worsening in any BVAS component
**BVAS Remission = BVAS score of zero and prednisone dose less than or equal to 10mg/day
About the Phase II CLEAR CCX168 Trial and Next Steps
The CLEAR trial is a randomized, double-blind, placebo-controlled, three-step Phase II trial being conducted at multiple study centers in Europe in up to approximately 60 patients. The clinical trial is designed to determine whether CCX168 can partially replace and potentially eliminate full-dose corticosteroids in patients with ANCA-associated renal vasculitis, given the toxicities of high-dose corticosteroid use.
The first two steps of the CLEAR trial have been completed. Patients are currently being enrolled in the third step of the CLEAR trial. ChemoCentryx plans to amend the protocol to include all three treatment groups: standard of care, CCX168 with low dose corticosteroids, and CCX168 with no corticosteroids, as conducted in Steps 1 and 2 of the CLEAR trial.
After meeting recently with the FDA, ChemoCentryx is currently finalizing its clinical development strategy in the U.S. More detailed information will be shared in the coming months.
About ANCA-Associated Vasculitis (AAV) and ANCA-Associated Renal Vasculitis (AARV)
ANCA-associated vasculitis (AAV) is a rare disease exemplified by a severe, often fatal autoimmune disease that is caused by autoantibodies called anti-neutrophil cytoplasmic antibodies (ANCA). AAV is characterized by inflammation that can affect many different organs and areas of the body, such as eyes, lung, sinuses, nerves and the kidney. When the kidneys are involved, it is called ANCA-associated renal vasculitis (AARV) or glomerulonephritis. AARV is the most common subset of AAV.
AARV patients experience decreased kidney function, leaking of blood and protein into the urine, and can lead to kidney failure, if left untreated. The morbidity and mortality remains high, with many patients suffering severe adverse effects of treatment. Consequences of treatment-related toxicity rival those of the underlying diseases.
The annual incidence and prevalence of AAV in Europe and the United States is estimated to be approximately 10 cases per million people per year and 100 per million people, respectively.
About ChemoCentryx
ChemoCentryx, Inc. is a clinical-stage biopharmaceutical company focused on discovering, developing and commercializing orally-administered therapeutics that target the chemokine and chemoattractant systems in order to treat autoimmune diseases, inflammatory disorders and cancer. The chemokine system is a biological network that regulates inflammation via a collection of secreted chemokine molecules, or ligands, and their specific cell surface receptors. Based on its proprietary drug discovery and drug development platform, ChemoCentryx has generated multiple clinical and preclinical-stage programs, each targeting distinct chemokine and chemoattractant receptors with different small molecule compounds. CCX140, a CCR2 inhibitor, has been shown to be safe and well tolerated while demonstrating clinical activity on glycemic indices in a Phase II clinical trial in type 2 diabetics, and is now in Phase II clinical development for the treatment of diabetic nephropathy. CCX168, a C5aR inhibitor, has recently completed the first two steps in an ongoing Phase II trial for the treatment of anti-neutrophil cytoplasmic antibody-associated renal vasculitis (AARV). CCX168 appears to be safe, well tolerated and successful in allowing both reduction and elimination of high-dose corticosteroids, part of standard of care for AARV patients, without compromising efficacy or safety during a 12-week treatment period. Vercirnon (also known as Traficet-EN or CCX282) is a specific CCR9 inhibitor for the treatment of inflammatory bowel disease. Other clinical programs include CCX872, a next generation CCR2 inhibitor, and CCX507, a next generation CCR9 inhibitor, both of which are in Phase I clinical testing and CCX354, a CCR1 inhibitor which successfully completed a Phase II clinical trial for the treatment of rheumatoid arthritis. ChemoCentryx also has several programs in advanced preclinical development.
Forward-Looking Statements
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" or "continue" or the negative of these terms or other comparable terminology are intended to identify forward-looking statements. These statements include statements regarding the potential of CCX168 for other indications. 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 ChemoCentryx business and other risks described in the Company's filings with the Securities and Exchange Commission ("SEC"). Investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and ChemoCentryx undertakes no obligation to revise or update this news release to reflect events or circumstances after the date hereof. Further information regarding these and other risks is included under the heading "Risk Factors" in ChemoCentryx's periodic reports filed with the SEC, including ChemoCentryx's Annual Report on Form 10-K for the year ended December 31, 2013 which is available from the SEC's website ( www.sec.gov ) under the heading "Investors." All forward-looking statements are qualified in their entirety by this cautionary statement. This caution is made under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995.
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Source: ChemoCentryx, Inc.
Susan M. Kanaya Senior Vice President, Finance and Chief Financial Officer or Markus J. Cappel, Ph.D. Chief Business Officer 650-210-2900 Media: Susan Kinkead Kinkead Communications 415-751-3611 Investor Relations: Angeli Kolhatkar Burns McClellan 212-213-0006
