-- Primary endpoint achieved: CCX168 demonstrates numerical superiority and achieves statistical significance in test for non-inferiority in BVAS response relative to standard of care --
-- Treatment with CCX168 successful in eliminating high-dose oral corticosteroids from current standard-of-care regimen without compromising efficacy --
-- CCX168 treatment resulted in rapid and pronounced improvements in BVAS, albuminuria, and other indicators of renal disease, as well as quality of life assessments --
-- CCX168 appears safe and well tolerated --
-- Company plans to advance CCX168 into Phase III development in AAV in 2016 --
-- Conference call and webcast with topline data presentation today at 8:30 a.m. Eastern Time --
MOUNTAIN VIEW, Calif., Jan. 06, 2016 (GLOBE NEWSWIRE) -- ChemoCentryx, Inc., (Nasdaq: CCXI ), a clinical-stage biopharmaceutical company developing orally-administered therapeutics to treat autoimmune diseases, inflammatory disorders, and cancer, today announced positive top-line data from its’ Phase II CLEAR trial with CCX168 in patients with anti-neutrophil cytoplasmic antibody (ANCA) -associated vasculitis, or AAV. CCX168 is a potent orally-administered small molecule that is a selective inhibitor of the complement C5a receptor, or C5aR. CCX168 is the lead drug candidate in the Company's orphan and rare disease program.
The Phase II CLEAR was designed to assess whether high dose chronic steroids used in the standard of care (SOC) regimen in AAV could be sharply reduced or eliminated, without compromising efficacy, by replacement with CCX168, a specific inhibitor of the C5aR. The complement component C5a and its receptor are thought to activate the autoimmune cells that destroy the blood vessels in AAV. Steroid elimination is desirable because steroids are strongly implicated in infections and other serious adverse events resulting in premature death in AAV, as well as long term toxicities, and cumulative organ damage.
The CLEAR trial met its primary endpoint based on the Birmingham Vasculitis Activity Score (BVAS) response at week 12 in patients receiving CCX168, compared to those patients receiving the high dose steroid-containing standard of care. Specifically, all treatment groups receiving CCX168 demonstrated a statistically significant (P=0.005) non-inferior clinical efficacy outcome when compared to SOC. The study contained two CCX168 treated groups: one group which received CCX168 with a low dose of steroid (i.e. one third the steroid in the SOC), in which the BVAS response was 86% at week 12 vs 75% for SOC; P=0.005 for non-inferiority. A separate group received CCX168 in the absence of any steroid; in this group the response was 81% (P=0.02 for non-inferiority). SOC treatment included a placebo to CCX168, and all treatment groups received a standard background immunosuppressant (cyclophosphamide or rituximab) as well. The primary endpoint of BVAS response was prospectively defined as a decrease from baseline of at least 50% in BVAS plus no worsening in any body system. BVAS measures AAV disease activity across all organ systems and is the most widely used and clinically validated outcome measure in AAV clinical trials. The greater the reduction in BVAS score, the greater the disease improvement.
Other beneficial changes were noted, including in pre-specified secondary endpoints:
- CCX168 exhibited a more rapid onset of improvement than SOC treatment, as evidenced by beneficial changes in proteinuria (measured as urinary albumin:creatinine ratio, or UACR); also rapid beneficial reductions from baseline in BVAS, as well as reductions in the levels of MCP-1 (a marker of kidney inflammation) found in the urine;
- Improvements in estimated glomerular filtration rate (eGFR) and hematuria were seen in all three treatment groups, indicating these disease activities did not require high dose chronic steroid administration to be controlled;
- Improvements in “Quality of Life” (as defined by the visual analogue scale of the EuroQOL-5D-5L measurement) were seen in CCX168 treatment groups, but not in the SOC group
Taken together, these results indicate that CCX168, a target-specific complement inhibitor, can replace chronic steroids in the treatment of AAV with at least equal efficacy. CCX168 also appeared safe and well tolerated in the trial. There were no observations that would prevent further clinical development of CCX168. The Company has also recently completed the long-term toxicology program with CCX168. The results provide support for chronic dosing of CCX168 in future clinical trials.
“For my patients with AAV, I would absolutely welcome a safer treatment with a rapid onset of action, retained existing efficacy outcomes, and which also would enable me to eliminate steroids from the current treatment regimen,” said David Jayne, M.D., from Addenbrooke’s Hospital in Cambridge, UK, and the principal clinical investigator for the trial. “High dose steroids are associated with a high incidence of morbidity, including infections, and since no steroid sparing therapies are approved today, I believe that there remains a significant need for additional, safer therapeutic options for AAV patients. As a C5aR inhibitor, CCX168 also has the potential for both steroid sparing and improved long-term kidney outcomes.”
“We are extremely pleased with the CLEAR trial results in 67 patients with AAV, particularly the ability of CCX168 to eliminate the need for chronic steroid administration, thus greatly lessening the harmful side-effects associated with long-term steroid usage. Based on these results, we believe CCX168 could change the treatment paradigm for patients with AAV,” said Thomas J. Schall, Ph.D., President and Chief Executive Officer of ChemoCentryx. “This is an important milestone for ChemoCentryx. We also look forward to upcoming results from the CLASSIC trial that, together with the results from the CLEAR trial, will collectively enable End-of-Phase II meetings with regulatory authorities, and initiation of our Phase III development program later this year.”
About the CLEAR Trial and CCX168 in ANCA-Associated Vasculitis
The European CLEAR trial is a 3-step randomized, double-blind, placebo-controlled Phase II trial designed to evaluate the safety and efficacy of CCX168 in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) on background cyclophosphamide or rituximab treatment. Efficacy measurements included global vasculitis disease activity, as measured by Birmingham Vasculitis Activity Score (BVAS), urinary albuminuria as measured by first morning urinary albumin:creatinine ratio, estimated glomerular filtration rate (eGFR) based on serum creatinine, hematuria (based on microscopic RBC count), and urinary MCP-1:creatinine ratio.
Across the three steps of the CLEAR trial, which was conducted in 11 countries in Europe, patients received one of three treatment regimens: (1) Placebo + cyclophosphamide or rituximab + full starting dose of prednisone (60 mg), (2) CCX168 30 mg twice daily + cyclophosphamide or rituximab + reduced starting dose of prednisone (20 mg), or (3) CCX168 30 mg twice daily + cyclophosphamide or rituximab + no prednisone. The cyclophosphamide regimen was 15 mg/kg intravenously every two to four weeks. The rituximab regimen was 375 mg/m 2 intravenously weekly for four weeks. The primary endpoint compared the two CCX168 treatment groups versus the standard of care control group, based on BVAS response.
The Company’s CCX168 AAV clinical development program also includes the ongoing North American Phase II CLASSIC trial. The CLASSIC trial is evaluating the safety and efficacy of twice daily, 10 or 30 mg CCX168, for 12 weeks, when added to the full-dose corticosteroid standard of care regimen plus cyclophosphamide or rituximab. Top-line data from the CLASSIC trial are expected in mid 2016.
About ANCA-Associated Vasculitis
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, or AAV, is a type of rare autoimmune inflammation caused by auto-antibodies. AAV encompasses granulomatosis with polyangiitis (GPA, formerly known as Wegener's granulomatosis), microscopic polyangiitis (MPA), eosinophilic polyangiitis (formerly Churg-Strauss syndrome) and renal limited vasculitis. By damaging the body’s small blood vessels, AAV can affect any organ system, but mostly involves the kidneys, lungs, and ear/nose/throat. This damage is caused by the destructive activity of inflammatory leukocytes in the body, with neutrophils considered to be the terminal effector cell. In AAV, C5a and its receptor, the target of CCX168, are involved in priming and activation of neutrophils, chemoattraction and vascular endothelial adhesion of these neutrophils and other leukocytes, and increased vascular permeability. By blocking the C5aR, CCX168 is thought to reduce vasculitis by reducing neutrophil activation, accumulation, and adhesion, as well as vascular permeability.
AAV affects approximately 40,000 people in the United States (with approximately 4,000 new cases each year) and greater than 75,000 people in Europe, with at least 7,500 new cases each year, and is currently treated with courses of non-specific immuno-suppressants (cyclophosphamide or rituximab) combined with high dose corticosteroid administration. Following initial treatment, up to 30 percent of patients relapse within six to 18 months, and approximately half of all patients will relapse within three to five years.
The current standard of care for AAV is associated with significant safety issues. First year mortality is approximately 11 to 18 percent. The single major cause of premature mortality is not disease related adverse events, but rather treatment-induced, including infection that is thought largely to be a consequence of corticosteroid administration. Indeed, the multiple adverse effects of courses of corticosteroid treatment (both initial courses and those that are repeated as a consequence of relapse) are major causes of both short-term and long-term disease and death. Such therapy-related adverse events contribute significantly to patient care costs, as well as to the diminution of quality of life for patients.
About CCX168
CCX168 is an orally-administered complement inhibitor, specifically targeting the C5a receptor (C5aR), which binds the complement fragment C5a. CCX168 is the lead drug candidate in the Company's orphan and rare disease program and is being developed for various autoimmune disorders including ANCA-associated vasculitis (AAV), atypical hemolytic uremic syndrome (aHUS) and immunoglobulin A nephropathy, or IgA nephropathy.
Conference Call and Webcast Information
The Company will host a conference call and webcast today, January 6, 2016 at 8:30 a.m. Eastern Time to discuss these Phase II trial results and to answer questions. To participate by telephone, please dial 877-303-8028 (Domestic) or 760-536-5167 (International). The conference ID number is 20543409. A live and archived audio webcast and the accompanying slides used in today’s conference call can be accessed through the Investors section of the Company's website at www.ChemoCentryx.com . The archived webcast will remain available on the Company's website for fourteen (14) days following the conference call.
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. 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 reduction and elimination of high-dose steroids, part of standard of care for AAV patients, without compromising efficacy or safety during a 12-week treatment period. CCX168 is also in Phase II studies for the treatment of atypical hemolytic uremic syndrome (aHUS) and immunoglobulin A nephropathy, or IgA nephropathy (IgAN). CCX872, a CCR2 inhibitor, successfully completed Phase I development and is in development for the treatment of non-resectable pancreatic cancer. CCX140, a distinct CCR2 inhibitor, successfully completed a Phase II clinical trial where it was shown to be safe and well tolerated while demonstrating statistically significant improvement in albuminuria in patients with diabetic nephropathy. Other clinical programs include CCX507, a next generation CCR9 inhibitor, which has successfully completed Phase I development, vercirnon (also known as Traficet-EN or CCX282) a specific CCR9 inhibitor for the treatment of inflammatory bowel disease, 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," "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 milestones in 2016 or whether CCX168 will be shown to be safe and 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 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 filed with the SEC March 13, 2015 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, Inc. CCXI-G
Susan M. Kanaya Senior Vice President, Finance and Chief Financial Officer investor@chemocentryx.com Media: Denise Powell denise@redhousecomms.com 510.703.9491 Investors: Kimberly Minarovich Burns McClellan 212.213.0006 kminarovich@burnsmc.com
