Primary Endpoint Achieved; Statistically Significant Reduction in Urinary Protein Over 52 Weeks
Improved Estimated Glomerular Filtration Rate Profile versus Standard of Care
Favorable Safety Profile for CCX140
Company to Host Conference Call and Webcast Today at 8:30a.m. ET
MOUNTAIN VIEW, Calif., Dec. 12, 2014 -- ChemoCentryx, Inc., (CCXI), a clinical-stage biopharmaceutical company focused on autoimmune diseases, inflammatory disorders and cancer, today announced positive top-line 52-week data from its Phase II clinical trial in diabetic nephropathy with CCX140, an inhibitor of the chemokine receptor known as CCR2.
The trial met its primary endpoint by demonstrating that treatment with 5 mg of CCX140 given orally once daily added to a standard of care regimen (SOC) of angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor II blocker (ARB) treatment resulted in a statistically significant (p=0.0148) reduction in urinary albumin creatinine ratio (UACR), beyond that achieved with SOC alone. High UACR is known to predict poor renal outcome. The maximum treatment effect (24 percent reduction) was reached at 12 weeks, and sustained reduction in albuminuria induced by CCX140 relative to SOC alone was observed over the full year, i.e., UACR at each one of the 10 time points over the 52-week treatment period in the patients who received 5 mg CCX140 continuously for 52 weeks, were below those of the SOC alone group. A dose of 10 mg CCX140 per day did not provide more improvement in albuminuria as compared to the 5 mg dose.
In addition, estimated glomerular filtration rate (eGFR) changes were assessed. Measuring eGFR is important in assessing long-term kidney function (over many months to years), and provides the basis for Phase III clinical trial registration endpoints. Numerous clinical trials with the current SOC (ACE inhibitors and ARBs) show that these attenuate the slope of decline of eGFR, and that this translates into a beneficial effect on clinical outcome parameters such as time to dialysis, with chronic multi-year treatment. Treatment with CCX140 improved the eGFR profile. Initial analysis showed that after an acute effect in eGFR in the CCX140 treatment groups in the first 12 weeks, there was a sustained attenuation in the slope of annual decline in eGFR. Such eGFR profiles have been associated with successful long-term clinical benefit in kidney outcomes with approved diabetic nephropathy drugs. The treatment group receiving 5 mg of CCX140 in addition to SOC showed an attenuated annual slope decline of 1.3 mL/min/1.73 m2, compared to SOC alone group, 2.3 mL/min/1.73 m2. The magnitude of slope improvement seen for CCX140 is consistent with drugs that have been previously approved for diabetic nephropathy.
CCX140 did not affect systemic blood pressure, suggesting that the beneficial effect of CCX140 is mediated locally in the kidney micro-environment, possibly through a beneficial reduction in renal inflammation. CCX140 appeared to be well tolerated with a low overall dropout rate over the 52-week treatment period (10 percent). No safety issues were observed that would prevent further clinical development of CCX140 in diabetic nephropathy.
"These positive data suggest that treatment with CCX140 may result in clinically meaningful improvements in kidney function when added to standard of care in patients with chronic kidney disease," said Thomas J. Schall, Ph.D., President and Chief Executive Officer, ChemoCentryx. "Given the positive improvements in albuminuria and eGFR observed in this clinical trial, we believe we have an effective dose of CCX140 to take forward into a Phase III clinical trial in diabetic nephropathy, and that we are well positioned to advance partnering discussions as well as an end of Phase II meeting with the FDA."
"Even with optimal current care, the residual risk in diabetic nephropathy patients for further decrease in renal function is still extremely high," said Prof. Dick de Zeeuw, M.D., Ph.D., in the Department of Clinical Pharmacy and Pharmacology at the University Medical Center in Groningen, The Netherlands. "The search for new drugs that add to standard of care ACE inhibitor and ARB treatment is therefore of utmost importance. To date, no great successes of new drugs on surrogates like blood pressure, albuminuria, or estimated glomerular filtration rate have been reported. These robust results with CCX140, in this context, are extremely relevant and promising, particularly if translated into preservation of renal function. CCX140 should definitely be tested in a Phase III trial."
The Company plans to present the full results of this clinical trial at upcoming medical meetings.
The objectives of the Phase II study, which took place at more than 90 sites across six European countries, were to determine the safety, tolerability and signs of clinical effect of CCX140 in patients with diabetic nephropathy. CCX140 was studied in a randomized, double-blind, placebo controlled clinical trial in 332 patients with residual albuminuria, despite having received an ACE inhibitor or ARB for at least eight weeks prior to screening for this trial. The original protocol had a 12-week treatment period that was extended to 52 weeks by protocol amendment. Of the 332 patients enrolled in the study initially, 102 patients were ineligible to re-enroll after the protocol amendment approval due to the length of time off treatment. As such 196 patients participated in the study extension to receive treatment for 52 weeks. The primary safety objective was evaluation of the safety profile of CCX140 based on the incidence of adverse events. The primary efficacy endpoint was the evaluation of the effect of CCX140 treatment over 52 weeks on first morning urinary albumin:creatinine ratio. Secondary objectives included evaluation of the effect of CCX140 on eGFR and HbA1c. At baseline, the mean age of the study population was 63 years, the median duration of type 2 diabetes was 14.5 years and the median duration of nephropathy was 3.3 years. The baseline mean urinary ACR for the population overall was 636 mg/g creatinine and baseline mean eGFR was 63 mL/min/1.73 m2. Baseline mean arterial blood pressure was 98 mm Hg.
About Diabetic Nephropathy
Diabetic nephropathy is a progressive kidney disease characterized primarily by proteinuria in patients with diabetes. Diabetic nephropathy is the leading cause of end-stage renal disease (ESRD) in the United States, resulting in the need for dialysis or kidney transplantation. Of the 26 million patients with chronic kidney disease, approximately 35 percent of those are patients with diabetes.
CCX140 is an inhibitor of the chemokine receptor known as CCR2. CCR2 is found on subsets of monocytes and macrophages, which are cells of the immune system believed to play an important role in inflammatory processes. Blocking CCR2 is intended to reduce the abnormal monocyte- and macrophage-driven inflammatory response implicated in renal diseases such as diabetic nephropathy. CCR2 may also have a direct role in the function of other specialized cells in the kidney, where its inhibition would correlate with a positive therapeutic effect.
Conference Call Information
The Company will host a conference call and webcast today, December 12, 2014 at 8:30 a.m. Eastern Time to discuss Phase II trial results and to answer questions. The live event will be accessible on the ChemoCentryx website beginning at 8:30 a.m. ET at www.ChemoCentryx.com, under the Investors section, or by calling 877-303-8028 (domestic) or 760-536-5167 (international). The conference ID number is 52903154
An archived webcast will be accessible via the Investors section of the Company's website atwww.ChemoCentryx.com. The webcast will remain available for thirty (30) days following the live call.
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, successfully completed a Phase II clinical trial where it was shown to be safe and well tolerated while demonstrating statistically significant improvements in kidney function in patients with diabetic nephropathy. CCX168, a C5aR inhibitor, is in Phase II development for the treatment of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). 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 AAV 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, currently in Phase I clinical development, CCX507, a next generation CCR9 inhibitor, which has successfully completed Phase I development 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.
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 whether CCX140 will be shown to be effective in Phase III clinical trials or obtain regulatory approval or the speed with which such approval might be obtained and statements regarding the ability of ChemoCentryx to successfully partner the development of CCX140. 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 Quarterly Report on Form 10-Q filed with the SEC November 6, 2014 and its other reports which are available from the SEC's website (www.sec.gov) and on ChemoCentryx's website (www.chemocentryx.com) 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.
Source: ChemoCentryx (CCXI-G)