Digestive Disease Week (DDW) 2010: Abstract 647. Presented May 4, 2010.
CCX282-B (Traficet-EN, ChemoCentryx) maintained remission of Crohn's disease over a 36-week period, according to new data presented here at Digestive Disease Week 2010.
These new data, from the randomized placebo-controlled Prospective Randomized Oral Therapy Evaluation in Crohn's Disease Trial (PROTECT)-1, build on a previous report from that trial showing that CCX282-B reduced the severity of Crohn's disease over a 12-week induction period.
Senior author Pirow Bekker, MD, from ChemoCentryx, Inc. in Mountain View, California, said that, "in general, results of PROTECT-1 compare favorably with studies of biologics, and we had a lower drop-out rate than in the biologic studies. We are hoping to get this compound to patients with Crohn's disease as soon as possible." He said that GlaxoSmithKline will control the development of the new drug.
CCX282-B, an investigational oral compound in late-stage development, specifically blocks chemokine receptor 9, which prevents inflammatory cells from getting to the site of inflammation in the digestive tract. "This compound is more selective than other agents used to treat Crohn's," Dr. Bekker said.
Results of the 12-week induction phase of PROTECT-1, reported in 2009, showed that CCX282-B reduced disease severity, defined as a decrease from baseline in the Crohn's Disease Activity Index score of at least 70 points over the course of 12 weeks of treatment. The drug also achieved a reduction in mucosal lesions.
Patients who were deemed responders in the 12-week induction study were rerandomized to placebo (n = 95) or CCX282-B 250 mg twice daily (n = 146) for 36 weeks to determine if remission could be maintained. At 36 weeks, CCX282-B maintained the remission rate at around 50%, whereas remission rate decreased progressively from 50% to 31% in the placebo group.
At 36 weeks, 47% of the patients treated with CCX282-B were in remission, compared with 31% who were treated with placebo (P = .01). In addition, 41% of the treatment group and 28% of the placebo group were in steroid-free remission at 36 weeks (P = .04). More patients in the treatment group than in the placebo group had a C-reactive protein level in the normal range (19% vs 9%; P = .04), and fewer required steroid rescue therapy (11% vs 21%; P = .04).
No serious infections developed in either group, and the type and percentage of serious adverse events were similar between groups.
"These data point to a broader role for this drug in treating autoimmune diseases," Dr. Bekker said.
Benefit of Oral Therapy With Investigational Compound
"Crohn's disease is debilitating and new therapies are welcome. TNF-alfa antagonists revolutionized treatment of the disease, but not all patients respond to those drugs," said Philip Schoenfeld, MD, associate professor of medicine at the University of Michigan in Ann Arbor.
Current therapeutic regimens for Crohn's disease require infusions of antibiologic agents every 8 weeks or subcutaneous injections. The opportunity to use an oral medication would improve compliance and facilitate maintenance of remission in these patients, he pointed out.
"These data need to be confirmed in appropriate phase 3 trials. Nevertheless, the availability of this new treatment is welcome in this difficult-to-treat population," Dr. Schoenfeld explained.
Probably the first use of this drug will be in nonresponders to available agents, but with more experience, it might turn out to be an alternative, he said.
Dr. Bekker is an employee of ChemoCentryx, which funded the study. Dr. Schoenfeld has served as consultant to Vertex Pharmaceuticals and Shire.
CCX282-B (Traficet-EN, ChemoCentryx) maintained remission of Crohn's disease over a 36-week period, according to new data presented here at Digestive Disease Week 2010.
These new data, from the randomized placebo-controlled Prospective Randomized Oral Therapy Evaluation in Crohn's Disease Trial (PROTECT)-1, build on a previous report from that trial showing that CCX282-B reduced the severity of Crohn's disease over a 12-week induction period.
Senior author Pirow Bekker, MD, from ChemoCentryx, Inc. in Mountain View, California, said that, "in general, results of PROTECT-1 compare favorably with studies of biologics, and we had a lower drop-out rate than in the biologic studies. We are hoping to get this compound to patients with Crohn's disease as soon as possible." He said that GlaxoSmithKline will control the development of the new drug.
CCX282-B, an investigational oral compound in late-stage development, specifically blocks chemokine receptor 9, which prevents inflammatory cells from getting to the site of inflammation in the digestive tract. "This compound is more selective than other agents used to treat Crohn's," Dr. Bekker said.
Results of the 12-week induction phase of PROTECT-1, reported in 2009, showed that CCX282-B reduced disease severity, defined as a decrease from baseline in the Crohn's Disease Activity Index score of at least 70 points over the course of 12 weeks of treatment. The drug also achieved a reduction in mucosal lesions.
Patients who were deemed responders in the 12-week induction study were rerandomized to placebo (n = 95) or CCX282-B 250 mg twice daily (n = 146) for 36 weeks to determine if remission could be maintained. At 36 weeks, CCX282-B maintained the remission rate at around 50%, whereas remission rate decreased progressively from 50% to 31% in the placebo group.
At 36 weeks, 47% of the patients treated with CCX282-B were in remission, compared with 31% who were treated with placebo (P = .01). In addition, 41% of the treatment group and 28% of the placebo group were in steroid-free remission at 36 weeks (P = .04). More patients in the treatment group than in the placebo group had a C-reactive protein level in the normal range (19% vs 9%; P = .04), and fewer required steroid rescue therapy (11% vs 21%; P = .04).
No serious infections developed in either group, and the type and percentage of serious adverse events were similar between groups.
"These data point to a broader role for this drug in treating autoimmune diseases," Dr. Bekker said.
Benefit of Oral Therapy With Investigational Compound
"Crohn's disease is debilitating and new therapies are welcome. TNF-alfa antagonists revolutionized treatment of the disease, but not all patients respond to those drugs," said Philip Schoenfeld, MD, associate professor of medicine at the University of Michigan in Ann Arbor.
Current therapeutic regimens for Crohn's disease require infusions of antibiologic agents every 8 weeks or subcutaneous injections. The opportunity to use an oral medication would improve compliance and facilitate maintenance of remission in these patients, he pointed out.
"These data need to be confirmed in appropriate phase 3 trials. Nevertheless, the availability of this new treatment is welcome in this difficult-to-treat population," Dr. Schoenfeld explained.
Probably the first use of this drug will be in nonresponders to available agents, but with more experience, it might turn out to be an alternative, he said.
Dr. Bekker is an employee of ChemoCentryx, which funded the study. Dr. Schoenfeld has served as consultant to Vertex Pharmaceuticals and Shire.
