GlaxoSmithKline (GSK) and ChemoCentryx, Inc. announced that the first patient with Crohn's disease has initiated treatment in the initial pivotal induction study comparing Traficet-EN, now designated GSK1605786 ('786), to placebo. This marks the start of the Phase III clinical development programme for '786 for the treatment of this serious and chronic disease.
'786 is a non-biologic, orally bioavailable CCR9 antagonist. CCR9 is a chemokine receptor that plays a central role in the inappropriate inflammatory response thought to underlie Crohn's disease. By blocking CCR9, '786 selectively impairs the movement of activated T cells that are involved in causing inflammation of the digestive tract. Its mode of action is believed to reduce inflammation while preserving normal immune function.
The Phase III clinical development programme, that is anticipated to include another pivotal induction study and a pivotal maintenance study, in addition to other studies, will evaluate the efficacy and safety of '786 for inducing a response and remission (reduction or disappearance of symptoms) and maintaining remission in over 2,500 patients with moderately-to-severely active Crohn's disease.
Earlier trial data of '786 for Crohn's disease have been presented at recent congresses including DDW and UEGW, 2010.
Study design
The initial pivotal induction study is a randomised, double-blind, placebo-controlled study that will involve approximately 600 patients to evaluate 500mg of '786 once daily or twice daily compared to placebo in patients with moderately-to-severely active Crohn's disease. The primary and key secondary endpoints are the proportion of subjects achieving a treatment-induced clinical response based on the Crohn's Disease Activity Index (CDAI) and the proportion of subjects achieving clinical remission.
About Crohn's disease
Crohn's disease is a chronic inflammatory condition of the digestive tract. It is estimated that the disease affects over 500,000 patients in Europe and North America. Patients suffer periods of flare-ups characterised by intense symptoms, interspersed with periods of relative remission where symptoms decrease or disappear. Following diagnosis, patients frequently need to continue therapy lifelong, layering additional therapies as flare-ups recur or persist in an effort to reduce symptoms. When medications no longer control symptoms, patients have few options beyond surgery. Alternative treatment options are needed that are convenient, oral and durable.
'786 is not licensed or approved in any country.
GSK has an exclusive license for the further development and worldwide commercialisation of '786 which represents the first product licensing opportunity from an ongoing collaboration with ChemoCentryx through GSK's Centre of Excellence for External Drug Discovery (CEEDD).
GlaxoSmithKline - one of the world's leading research-based pharmaceutical and healthcare companies - is committed to improving the quality of human life by enabling people to do more, feel better and live longer.
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 lead compound, Traficet-EN (GSK'786), a specific CCR9 antagonist, completed a multi-national clinical trial, called PROTECT-1 in patients with moderately-to-severely active Crohn's disease, and is now in Phase III clinical development. Other clinical programs include CCX140, which targets the CCR2 receptor, in Phase II clinical development for the treatment of type 2 diabetes mellitus and associated complications; CCX354, a CCR1 antagonist in a Phase II clinical trial for the treatment of rheumatoid arthritis; CCX168, a C5aR antagonist, that completed Phase I clinical development and is anticipated to enter Phase II clinical trials in 2011; and CCX832, a ChemR23 antagonist, in Phase I clinical development. ChemoCentryx also has several programs in preclinical development.