Results from a Phase II study released Monday suggest that Abbott Laboratories' ABT-874, a fully human anti-interleukin-12 monoclonal antibody, showed significant differences in response and remission rates in patients with active Crohn's disease (highest response rate 75 per cent at week 7; highest remission rate 50 per cent at week 19) compared to placebo in one arm of the study. ABT-874 is a new, investigational agent designed to target and neutralize IL-12, a known mediator of inflammation in Crohn's disease. The data was presented at the Digestive Disease Week annual meeting in New Orleans.
"These initial data are very exciting and suggest that anti-IL-12 therapy offers promise as a new approach in biologic treatment for Crohn's," said Charles O. Elson, M.D., Professor of Medicine and Microbiology, University of Alabama at Birmingham.
Seventy-nine patients with active Crohn's disease were enrolled in a randomized, double-blind, placebo-controlled trial of ABT-874. Patients were randomly assigned to receive seven weekly subcutaneous injections of ABT-874 (1 mg/kg or 3mg/kg or placebo) either with a four week interval between the first and second injection (Cohort 1) or with no interruption (Cohort 2). All patients were followed for 18 weeks after the final injection of study drug.
Patients in Cohort 2 who received 3mg/kg of ABT-874 showed a significant difference in response rates and remission rates compared to patients who received placebo. At the end of treatment (7 weeks), the response rate for this group was 75 per cent and the remission rate was 38 per cent. After 12 weeks of follow-up (week 19), 50 per cent of patients were in remission with 69 per cent achieving a clinical response.
Participants had active Crohn's disease as indicated by a Crohn's Disease Activity Index (CDAI) score of 220-450. CDAI is a weighted composite score of eight clinical factors, including daily number of liquid or very soft stools, severity of abdominal pain, level of general well-being, presence of extraintestinal manifestations or abdominal mass, use of anti-diarrheal agents, hematocrit and decrease in standard body weight. Results were measured by changes in CDAI score. Remission was defined as a CDAI < 150 points and clinical response as a decrease in the CDAI score of > 100 points from baseline.
The response and remission rates for patients receiving ABT-874 in Cohort 1 were not significantly different from the placebo group. In both groups, antibody-related adverse events were similar to placebo except for local injection site reactions.
"We're highly encouraged with the performance of ABT-874 we have seen so far," said Elliot Chartash, M.D., global project head, Immunoscience Development, Abbott Laboratories. "These data are encouraging as we assess the potential of ABT-874 to provide benefit to patients suffering from Crohn's. We also are continuing to explore the role of anti-IL-12 therapy in other autoimmune conditions, including multiple sclerosis."
ABT-874 is an investigational agent designed to target and neutralize interleukin-12 (IL-12), a protein that regulates inflammatory response. IL-12 is associated with a number of chronic inflammatory autoimmune disorders, including Crohn's disease. ABT-874 is currently being evaluated in Crohn's disease and in Phase II studies for multiple sclerosis (MS), which are currently underway.
Crohn's disease is a serious chronic and inflammatory disease of the gastrointestinal (GI) tract that affects approximately 500,000 Americans and is typically diagnosed before age 30. Common symptoms of the disease include diarrhea, cramping, abdominal pain, weight loss, fever, and in some cases rectal bleeding. Currently, there is no cure for Crohn's disease.
Abbott is focused on the discovery and development of innovative treatments for immunologic diseases. The Abbott Bioresearch Center, founded in 1989 in Worcester, Massachusetts, United States, is a world-class discovery and basic research facility committed to finding new treatments for autoimmune diseases.