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Open Label Study of Infliximab Demonstrates Efficacy in Pediatric Ulcerative Colitis

Chicago, IL, May 9, 2011 – Data from a Phase 3 randomized, multicenter, open-label study demonstrated clinical response with infliximab (Remicade) in the treatment of pediatric patients with moderately to severely active ulcerative colitis (UC), and showed a safety profile consistent with previous clinical trials conducted in an adult population. The pediatric UC findings, presented today at Digestive Disease Week, showed Remicade induced clinical response in 73 percent of patients aged 6-17 years at week 8, the primary endpoint of the trial. Remicade received U.S. Food and Drug Administration (FDA) approval for the treatment of adults with moderately to severely active UC in September 2005 and in October 2006, Remicade received FDA approval for maintaining clinical remission and mucosal healing indications in adults living with UC.

UC is a chronic inflammatory bowel disease (IBD) of the colon. It is estimated that 1.4 million Americans have IBD with the number evenly split between UC and Crohn’s disease. An estimated 150,000 children under age 17 are living with debilitating symptoms of IBD.1

“The results of this study are consistent with findings from the Active Ulcerative Colitis (ACT) trials, which evaluated Remicade in the treatment of adults with ulcerative colitis,” said Jeffrey Hyams, Head of the Division of Digestive Diseases and Nutrition at Connecticut Children’s Medical Center and Professor of Pediatrics at University of Connecticut School of Medicine, and lead study investigator. “UC can be a devastating disease, particularly for children and adolescents. It is encouraging to see such promising results in a patient population that is in need of additional treatment options.”

In December 2010, Centocor Ortho Biotech Inc. submitted a supplemental Biologics License Application (sBLA) to the FDA requesting the approval of Remicade (infliximab) for the treatment of moderately to severely active UC in pediatric patients who have had an inadequate response to conventional therapy. The Remicade pediatric UC sBLA was designated priority review by the FDA. On November 12, 2003, the FDA designated Remicade orphan drug status for the treatment of pediatric UC.

A total of 60 patients with moderately to severely active UC (Mayo score of 6-12, with an endoscopy subscore =2) were enrolled in the trial. Patients had previously failed to respond to or tolerate treatment with 6-mercaptopurine (6-MP), azathioprine (AZA), corticosteroids, and/or 5-aminosalicylate (5-ASA) and were administered Remicade 5 mg/kg at weeks 0, 2, and 6. At week 8, Remicade induced clinical response according to the Mayo score in 73.3 percent of patients, the primary endpoint of the trial. The Mayo score is a 12-point clinical assessment and colonoscopy-based measure of disease activity. Also at week 8, 40 percent of patients were in clinical remission by the Mayo score and 33.3 percent were in remission by the validated, non-invasive clinical assessment of disease activity in children, the Pediatric UC Activity Index (PUCAI). In addition, 68.3 percent of patients achieved mucosal healing at week 8.

Patients achieving clinical response at week 8 (n=45) were randomized to receive Remicade 5 mg/kg every eight weeks through week 46 (n=22) or every 12 weeks through week 42 (n=23). At week 54, twice as many patients in the group that received Remicade every eight weeks (38.1 percent) achieved remission by the PUCAI compared with the group that received Remicade every 12 weeks (18.2 percent), though this did not reach statistical significance (P = 0.146) due to the small sample sizes. More patients on corticosteroids at baseline were in remission and off corticosteroids at week 54 in the maintenance group that received Remicade every eight weeks (38.5 percent) than in the every 12-week maintenance group (0 percent).

About the Study
The Phase 3 randomized, multicenter, open-label trial was designed to evaluate the efficacy of a 3-dose Remicade regimen in inducing clinical response in pediatric patients with moderately to severely active UC and to evaluate the safety of Remicade during induction and maintenance treatment. A total of 60 patients, aged 6-17, with a median disease duration of 1.4 years were included in the study. Patients had a median Mayo score of 8.0, and median PUCAI score of 55. All patients had failed to respond to or tolerate treatment with 6-MP, AZA, corticosteroids and/or 5-ASA. Patients received Remicade 5 mg/kg at weeks 0, 2, and 6. The primary endpoint, clinical response at week 8, was defined as a decrease from baseline in the Mayo score of at least 30 percent and at least 3 points, with a decrease in rectal bleeding subscore of at least 1 or a rectal bleeding subscore of 0/1. Patients who achieved clinical response at week 8 were randomized to receive Remicade 5 mg/kg every 8 weeks through week 46 or every 12 weeks through week 42. Non-responders were discontinued from study agent.

Remicade was generally well tolerated. The proportions of patients experiencing serious adverse events were similar across the maintenance groups (18.2% and 21.7% in the every 8 week and every 12 week groups, respectively). Similarly the proportions of patients experiencing infusion reactions were also similar (18.2% and 13.0% in the every 8 week and every 12 week groups, respectively). No deaths, malignancies, opportunistic infections, tuberculosis or delayed hypersensitivity reactions were reported.

About Ulcerative Colitis
Ulcerative colitis (UC), a chronic inflammatory bowel disease affecting nearly 700,000 people in the U.S., is marked by the inflammation and ulceration of the colonic mucosa, or innermost lining, which may lead to bloody stools, severe diarrhea and frequent abdominal pain. Tiny open sores, or ulcers, form on the surface of the lining where they bleed and produce pus and mucus. Symptoms of the disease may lead to loss of appetite, subsequent weight loss, and fatigue. UC is a chronic disease, and there is no cure. Although progress has been made in IBD research, investigators do not know what causes this disease.

Source: Centocor Ortho Biotech Inc

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