NEW YORK (Reuters Health) May 04 - The oral chemokine receptor antagonist Traficet-EN can induce long-term remission of moderate to severe Crohn's disease, according to phase IIb/III trial results presented today at Digestive Disease Week 2010 in New Orleans.
"Traficet-EN specifically targets chemokine receptor 9, which is present on inflammatory cells involved in Crohn's disease and ulcerative colitis," presenter Dr. Pirow Bekker told Reuters Health. "It sorts the inflammatory cells so they don't get to the site of inflammation and leaves the rest of the immune system unaltered."
"This is important because it has potential safety advantages compared to more general immunosuppressive drugs such as corticosteroids, azathioprine or the anti-TNFs," he added.
The PROTECT-1 trial involved 436 patients with Crohn's Disease Activity Index (CDAI) scores between 250 and 450.
Dr. Bekker, from ChemoCentryx, Inc. in Mountain View, California, and colleagues first randomized their subjects to receive one of three doses of Traficet-EN or placebo for 12 weeks, followed by a 4-week open-label phase. The response rate (defined as a decrease of at least 70 points on the CDAI) was 61% with Traficet-EN compared with 40% with placebo, Dr. Bekker said.
Then, for the 36-week maintenance phase, the researchers re-randomized 241 responders to receive either Traficet-EN 250 mg twice daily (n = 146) or placebo (n = 95).
The proportion of subjects in remission (i.e., with a CDAI no higher than 150) remained steady at about 50% in the Traficet-EN group, while it fell progressively in the placebo group. At the end of the trial, 47% of subjects on active treatment were in remission compared with 31% on placebo (p = 0.01).
Also, according to the meeting abstract, significantly more patients in the Traficet-EN arm were in corticosteroid-free remission and had normal C-reactive protein levels. There was no increase in serious adverse events with active treatment.
Dr. Bekker noted that remission rates were similar to those reported for drugs targeting tumor necrosis factor, but that the 1-year dropout rate - at 22% in their study - was much lower than rates of up to 60% with anti-TNF agents.
"If studies continue to show a good safety profile and good efficacy profile, then it has a good chance to be (indicated) for use early on in the disease," Dr. Bekker said.
"We have several compounds targeting other chemokine receptors, so PROTECT-1 provides some validation for this approach and points to potentially broader application of chemokine receptor antagonists to treat major inflammatory and autoimmune diseases," he added.
"Crohn's disease has seen a revolution of new therapies in the last 10 to 20 years with the anti-TNF agents," Dr. Philip Schoenfeld, from the University of Michigan, Ann Arbor, told Reuters Health. "But not all patients respond to these drugs, making an oral chemokine receptor antagonist an attractive new option." Dr. Schoenfeld was not involved in the PROTECT-1 trial.
"Traficet-EN specifically targets chemokine receptor 9, which is present on inflammatory cells involved in Crohn's disease and ulcerative colitis," presenter Dr. Pirow Bekker told Reuters Health. "It sorts the inflammatory cells so they don't get to the site of inflammation and leaves the rest of the immune system unaltered."
"This is important because it has potential safety advantages compared to more general immunosuppressive drugs such as corticosteroids, azathioprine or the anti-TNFs," he added.
The PROTECT-1 trial involved 436 patients with Crohn's Disease Activity Index (CDAI) scores between 250 and 450.
Dr. Bekker, from ChemoCentryx, Inc. in Mountain View, California, and colleagues first randomized their subjects to receive one of three doses of Traficet-EN or placebo for 12 weeks, followed by a 4-week open-label phase. The response rate (defined as a decrease of at least 70 points on the CDAI) was 61% with Traficet-EN compared with 40% with placebo, Dr. Bekker said.
Then, for the 36-week maintenance phase, the researchers re-randomized 241 responders to receive either Traficet-EN 250 mg twice daily (n = 146) or placebo (n = 95).
The proportion of subjects in remission (i.e., with a CDAI no higher than 150) remained steady at about 50% in the Traficet-EN group, while it fell progressively in the placebo group. At the end of the trial, 47% of subjects on active treatment were in remission compared with 31% on placebo (p = 0.01).
Also, according to the meeting abstract, significantly more patients in the Traficet-EN arm were in corticosteroid-free remission and had normal C-reactive protein levels. There was no increase in serious adverse events with active treatment.
Dr. Bekker noted that remission rates were similar to those reported for drugs targeting tumor necrosis factor, but that the 1-year dropout rate - at 22% in their study - was much lower than rates of up to 60% with anti-TNF agents.
"If studies continue to show a good safety profile and good efficacy profile, then it has a good chance to be (indicated) for use early on in the disease," Dr. Bekker said.
"We have several compounds targeting other chemokine receptors, so PROTECT-1 provides some validation for this approach and points to potentially broader application of chemokine receptor antagonists to treat major inflammatory and autoimmune diseases," he added.
"Crohn's disease has seen a revolution of new therapies in the last 10 to 20 years with the anti-TNF agents," Dr. Philip Schoenfeld, from the University of Michigan, Ann Arbor, told Reuters Health. "But not all patients respond to these drugs, making an oral chemokine receptor antagonist an attractive new option." Dr. Schoenfeld was not involved in the PROTECT-1 trial.