ChemoCentryx Reports Additional New Data from the PROTECT-1 Study Demonstrating Traficet-EN's Effectiveness in Maintaining Remission in Patients with Crohn's Disease
MOUNTAIN VIEW, Calif., Dec. 7 In addition to data released in late November, ChemoCentryx, Inc., announced today more data from the Company's PROTECT-1 (the Prospective Randomized Oral Therapy Evaluation in Crohn's disease Trial) of Traficet-EN(TM) (CCX282-B) in patients with moderate-to-severe Crohn's disease. While the earlier announcement concerned the Induction period of the study, new data from the Maintenance period of the study showed that a statistically significant number of patients receiving continuous therapy of Traficet-EN versus placebo for 36 weeks were in clinical remission of Crohn's disease, defined as a score of 150 points or less in the Crohn's Disease Activity Index (CDAI). At week 36, a statistically significant percentage of patients receiving Traficet-EN versus placebo were in corticosteroid-free remission. Traficet-EN continued to be safe and well-tolerated after extended use. Additionally, conclusive evidence was provided that the involvement of the CCR9 and its chemokine ligand (TECK) in inflammatory bowel disease (IBD) is not just restricted to the small bowel, but is relevant to inflammation of the large bowel as well.
The new Crohn's disease clinical remission findings, as well as the expanded understanding of the role of CCR9 and its ligand TECK in the gastrointestinal system (GI) tract, were highlighted in poster and oral presentations titled "PROTECT-1 Maintenance Phase Study Results Demonstrate Efficacy of the Intestine-Specific Chemokine Receptor Antagonist CCX282-B (Traficet-EN) in Crohn's Disease" and "CCR9 Inhibition in the Treatment of Colonic Inflammation" at the 2009 Advances in Inflammatory Bowel Diseases, Crohn's & Colitis Foundation's Clinical & Research Conference in Hollywood, Florida.
Traficet-EN is an orally-active antagonist of the chemokine receptor known as 'CCR9', which is selectively expressed by inflammatory T cells that migrate to the digestive tract in a process that ultimately results in the persistent inflammation underlying IBD. Targeting the CCR9 chemokine receptor represents a novel approach for the treatment of Crohn's disease and other inflammatory disorders of the GI system.
"Current approaches to the treatment of Crohn's disease often result in serious side effects, especially following long-term use of these drugs," said Pirow Bekker, M.D., Ph.D., Senior Vice President, Medical and Clinical Affairs of ChemoCentryx. "These results suggest that Traficet-EN has the potential to keep Crohn's patients in remission without complications such as broad immunosuppression associated with current therapies."
"Data generated from these two studies are groundbreaking in nature and have the potential to revolutionize the way Crohn's disease and ulcerative colitis are treated," said Thomas J. Schall, Ph.D., President and Chief Executive Officer of ChemoCentryx. "We are particularly pleased that we have for the first time definitively identified the CCR9 chemokine ligand in the large bowel which will broaden the scope of digestive tract disorders that Traficet-EN could potentially treat successfully."
Results for PROTECT-1 Maintenance Period of Study
Over the course of the Maintenance period, the remission rate in the Traficet-EN group remained between 47% and 50%, whereas the remission rate continued to decrease in the placebo group. At week 36, 47% of subjects in the Traficet-EN group were in remission compared to 31% in the placebo group (p=0.01). Furthermore, at week 36, 41% of patients in the Traficet-EN group were in corticosteroid-free remission compared to 28% in the placebo group (p=0.04).
Study Design for PROTECT-1 Trial
The randomized, placebo-controlled, double-blind clinical trial of 436 patients is comprised of three discrete periods which allows for evaluation of efficacy and safety of Traficet-EN in inducing a clinical response or remission, as well as maintaining response/remission in Crohn's disease over a combined total of 12 months. The 12-week Induction period of the study is followed by a 4-week, open-label period, during which all subjects receive Traficet-EN. Patients who achieve a pre-specified 70-point or greater reduction in CDAI are re-randomized to active drug or placebo for an additional 36-week Maintenance period, thereby permitting an evaluation of the drug's ability to maintain a treatment response. CDAI is a research tool used for determining a patient's level of disease activity and is the key measure regarded by regulatory agencies as an appropriate endpoint to assess the efficacy of a drug for the treatment of Crohn's disease.
Study Results and Methods for CCR9 and TECK in Large Bowel Inflammatory Bowel Disease
In studies done to test the prevailing notion that TECK protein and CCR9 only function in the small bowel, ChemoCentryx scientists demonstrated TECK protein is readily detectable in human colon samples from both normal subjects and patients with IBD. Furthermore, they assessed colonic tissues from mice which spontaneously develop inflammatory colitis owing to a genetic predisposition. TECK chemokine expression within the colon of pre-symptomatic mice were significantly increased compared to control, normal, mice (0.2 +/- 0.09 pg/ug protein and 0.04 +/- 0.0006 pg/ug protein, respectively; p = 0.05) and furthermore, in mice displaying severe symptoms, TECK levels were significantly increased compared to pre-symptomatic animals (16.51 +/- 3.9 pg/ug protein; p=0.05 vs pre-symptomatic mice). Also, pharmacologic inhibition of CCR9 in these animals resulted in marked reduction of their colitis.
About Traficet-EN(TM) (CCX282-B)
Traficet-EN is a small molecule, orally bioavailable drug that is administered in capsule form and which is believed to control the inappropriate immune system response underlying inflammatory bowel disease (IBD) by blocking the CCR9 chemokine receptor. In adults, CCR9 is a highly specific receptor expressed by T cells that migrate to the digestive tract. The trafficking of T cells to the small and large intestine causes persistent inflammation that may result in Crohn's disease or ulcerative colitis -- the two principal forms of IBD. In preclinical studies, the compound worked both therapeutically and prophylactically in models of Crohn's disease and ulcerative colitis. ChemoCentryx has completed six Phase I clinical trials and one four-week Phase II Crohn's disease trial of Traficet-EN at doses up to 1000 mg twice daily, demonstrating that the product candidate is well-tolerated and appropriate for once-daily or twice-daily oral dosing. Traficet-EN may offer advantages over existing therapeutic approaches for Crohn's disease by potentially offering reduced side effects and convenient oral dosing to patients. Traficet-EN is being developed under a strategic alliance with GlaxoSmithKline's Center of Excellence for External Drug Discovery (CEEDD).
About Crohn's Disease
Crohn's disease is a chronic inflammatory condition of the gastrointestinal tract. It is estimated that the disease affects over 500,000 patients in Europe and North America. Patients suffer periods of flare-ups characterized by intense symptoms, interspersed with periods of relative remission where symptoms decrease or disappear. As Crohn's disease is a chronic condition, patients continue on therapy from the time of diagnosis over the course of a lifetime, layering additional therapies as flare-ups recur or persist in an effort to reduce symptoms. When medications can no longer control symptoms, patients have few options beyond surgery.
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 network of secreted chemokine molecules, or ligands, and cell surface receptors that regulates inflammation. Based on its proprietary drug discovery and drug development platform, ChemoCentryx has internally 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, a specific CCR9 antagonist, completed a Phase II/III multi-national clinical trial, called PROTECT-1, in patients with moderate-to-severe Crohn's disease. CCX025, also a CCR9 antagonist, successfully concluded a Phase I clinical program. Additional clinical programs include the development of CCX140, which targets the CCR2 receptor, expected to enter Phase II clinical development in the first quarter of 2010 for the treatment of type 2 diabetes mellitus, and CCX354, a CCR1 antagonist expected to enter Phase II by year end for the treatment of rheumatoid arthritis. ChemoCentryx also has several programs in preclinical development. ChemoCentryx is privately held. For more information, please refer to www.chemocentryx.com.
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SOURCE ChemoCentryx, Inc.
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