ChemoCentryx Reports Clinical Efficacy for CCX354, a Novel CCR1 Inhibitor in a Phase II Study in Patients with Rheumatoid Arthritis

MOUNTAIN VIEW, Calif., Nov. 8, 2011 /PRNewswire/ -- ChemoCentryx, Inc., today announced that it reported positive Phase II results for CCX354 at the Annual Meeting of the American College of Rheumatology (ACR).  CCX354 is an orally-active small molecule that specifically targets and inhibits the chemokine receptor known as CCR1, which is implicated in the development and progression of rheumatoid arthritis (RA).  Results showed that CCX354 was safe and well tolerated by patients with RA in this clinical trial, and demonstrated clinical and biological activity at a dose of 200 mg once daily.  These data were highlighted today in a late-breaker oral presentation in Chicago entitled "Safety and Efficacy of Oral Chemokine Receptor 1 Antagonist CCX354-C in a Phase II Rheumatoid Arthritis Study".

"The initial cloning and characterization of CCR1 as well as the chemokine known as RANTES, one of the main ligands for CCR1, was accomplished by the founder of ChemoCentryx over twenty years ago," stated Paul-Peter Tak, M.D., Ph.D., Lead Investigator and Professor at AMC/University of Amsterdam, currently also Senior Vice President/Head, Therapy Area ImmunoInflammation at GlaxoSmithKline.  "Although there has been strong evidence implicating CCR1 in the pathology of RA, this is the first time that an investigational CCR1 antagonist has successfully demonstrated clinical efficacy in patients with this disease."

The results reported from this study, known as the CARAT-2 clinical trial, show that patients who met inclusion criteria at the start of dosing (Day 1 eligible) had an ACR20 response at Week 12 of 56% in patients receiving 200 mg CCX354 once daily compared to 44% in patients receiving 100 mg twice daily, and 30% in patients receiving placebo. The difference between 200 mg once daily and placebo was statistically significant (p=0.014). The decrease in CRP, a marker of inflammation, was statistically significant in the 200 mg QD group compared to placebo at Week 12 (p=0.023).  ACR50, ACR70, DAS28-CRP, and ACR component results indicated greatest efficacy in the 200 mg daily dose group.  Decreases in bone turnover markers C-telopeptide (CTx), procollagen type I N-terminal propeptide (PINP), and osteocalcin were more pronounced in the CCX354-C groups compared to placebo, and reaching statistically significant improvements at many time points during the study. Clinical responders had higher plasma CCX354 concentrations than non-responders.  CCX354 was well tolerated by patients in this study.

Study Design

This Phase II study named CARAT-2 (CCR1 Antagonist in Rheumatoid Arthritis Trial-2) was a 160-patient multinational, randomized, double-blind, placebo-controlled RA clinical trial.  Patients had moderate to severe RA, were on stable methotrexate treatment for at least 8 weeks, had >/= 8 swollen and tender joint counts, and CRP >/= 5 mg/L at study entry.  Patients received double-blind placebo twice daily (N=54), 100 mg CCX354 twice daily (N=53) or 200 mg CCX354 once daily (N=53) orally for 12 weeks.  Safety and tolerability were primary endpoints, and secondary endpoints included RA disease response measurements:  ACR, DAS28, CRP, and ESR, as well as bone turnover markers, CTx, PINP, and osteocalcin.

CCX354 and Rheumatoid Arthritis (RA)

CCX354 is a potent and selective antagonist of CCR1, a chemokine receptor that drives the recruitment of certain inflammatory cells including populations of monocytes and macrophages into the joints of patients with RA.  By selectively blocking the CCR1 receptor, CCX354 is designed to reduce the infiltration of inflammatory cells into the joints of RA patients and inhibiting the inflammation, swelling, pain and associated joint destruction while minimizing the potential for off-target effects, thus providing a wider therapeutic window than currently approved therapies. RA is estimated to affect more than two million people in the U.S. and is a leading cause of morbidity, disability and reduced work ability. The exact cause of RA is unknown, but is believed to reflect the body's immune system attack on the synovium, the tissue that lines the joints.

CCX354 is one of four drug candidates that have been discovered and developed by ChemoCentryx that are also part of an alliance between the Company and GlaxoSmithKline (GSK).  Successful completion of CARAT-2 triggered GSK's option rights under the collaboration agreement, and ChemoCentryx expects GSK's decision whether to exercise its option to obtain a license to further develop and commercialize CCX354 by the end of 2011.

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. ChemoCentryx's most advanced drug candidate, CCX282-B (Traficet-EN, now designated GSK1605786, also known as GSK'786), a specific CCR9 inhibitor, completed a multi-national clinical trial, called PROTECT-1, in patients with moderate-to-severe Crohn's disease, where it demonstrated the ability to induce a clinical response and to maintain clinical remission, and is now in Phase III clinical development. ChemoCentryx's lead independent drug candidate, CCX140-B, 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. Other clinical programs include CCX354, a CCR1 inhibitor which successfully completed a Phase II clinical trial for the treatment of rheumatoid arthritis; CCX168, a C5aR inhibitor, in Phase II clinical development for the treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis; and CCX832, a ChemR23 antagonist in Phase I clinical development. ChemoCentryx also has several programs in advanced preclinical development.

Certain statements in this press release may constitute "forward-looking statements". These statements are made on the basis of current expectations, forecasts and assumptions that involve risks and uncertainties, including, but not limited to, economic, competitive, governmental and technological factors outside of our control, that may cause our business, strategy or actual results to differ materially from those expressed or implied. We do not intend, and undertake no obligation, to update any forward-looking statements, whether as a result of new information, future events or otherwise.

SOURCE ChemoCentryx, Inc.