London, England, (May 25, 2011) – Results from a Phase 2 multicenter, randomized, double-blind, proof-of-concept and dose-finding study showed that treatment with sirukumab (CNTO 136) improved signs and symptoms of rheumatoid arthritis (RA) in patients with active disease despite treatment with methotrexate (MTX). Findings from Part A of the two-part trial presented at the 2011 European League Against Rheumatism (EULAR) Congress showed that a greater proportion of patients receiving sirukumab achieved a significantly greater reduction in Disease Activity Score 28 (DAS28 CRP) at week 12, the primary endpoint of the study. All patients in this study were continued on MTX. Sirukumab is a human monoclonal IgG1 kappa antibody that targets the cytokine interleukin (IL)-6 and is currently in Phase 2 study investigating its use in moderately to severely active RA as a subcutaneously administered treatment.
RA is a chronic, systemic inflammatory condition that is characterized by symptoms that include pain, stiffness and inflammation, and in some cases, joint destruction and disability. It is estimated 1.5 million Americans  and more than 23.5 million people worldwide  are affected by the condition, for which there is no cure.
“Not all patients respond to initial treatment, and in my experience a proportion of patients receiving currently available therapies will either have an inadequate response or lose response over time,” said Josef Smolen, M.D., Professor of Medicine at the Department of Internal Medicine at the Medical University of Vienna, Austria, and study investigator. “There continues to be a need for additional therapeutic options for the treatment of rheumatoid arthritis, a serious, progressive autoimmune disease. The results we have seen to date with sirukumab are promising, and we look forward to seeing future data from the ongoing clinical studies.”
Investigators reported data from Part A of the study in which patients remained on their background MTX dose and were randomized to receive subcutaneous (SC) injections of sirukumab 100 mg or placebo once every two weeks from week 0 to week 10. At week 12, an interim analysis showed 82 percent of patients in the sirukumab group achieved good or moderate DAS28 CRP response (38 percent good and 44 percent moderate) compared with 32 percent (11 percent good and 21 percent moderate) of patients receiving placebo plus MTX (P = 0.015). By week 12, at least a 20 percent improvement in American College of Rheumatology Scores (ACR20) was seen in 75 percent of sirukumab-treated patients compared with 21 percent of patients receiving placebo plus MTX (P = 0.002). Findings also showed participants receiving sirukumab demonstrated improvements in ACR components and decreased morning stiffness.
Treatment with sirukumab was generally well-tolerated through 10 weeks of treatment. Three patients discontinued the study before week 12 due to an adverse event (AE): 1 serious AE of cellulitis staphylococcal that was resolved (sirukumab patient), 1 AE of pneumonia (sirukumab patient) and 1 AE of worsening of RA (placebo patient). No deaths, cardiovascular events or gastrointestinal perforations occurred. Notable laboratory abnormalities were: asymptomatic Grade 3 neutropenia (absolute neutrophil count 660) and Grade 3 elevated alanine amino transferase (peak: 7-8 times upper limit of normal) in 1 sirukumab patient each, and hypercholesterolemia in 2 of 14 placebo patients (14 percent) versus 3 of 5 sirukumab patients (60 percent) among 19 patients overall with normal baseline total cholesterol (less than 200 mg/dL or 5.17 mmol/L).
“We are very optimistic about the results that we have seen thus far with sirukumab, a human antibody directed against IL-6,” said Jerome A. Boscia, M.D., Head of Immunology Development, Centocor Research & Development, Inc. “We believe sirukumab has the potential to offer physicians an important new therapeutic option for the treatment of rheumatoid arthritis in the future.”
About Rheumatoid Arthritis
Rheumatoid Arthritis is a chronic, systemic inflammatory condition that is often characterized by symptoms that include pain, stiffness and inflammation, and in some cases, joint destruction and disability. It is estimated that 1.5 million Americans1 and more than 23.5 million people worldwide2 are affected by the condition, for which there is no cure.
About the Phase 2 Study
The Phase 2 study is a two-part, multicenter, randomized, double-blind, parallel-group, placebo-controlled, proof-of-concept and dose-finding study evaluating the efficacy and safety of sirukumab administered subcutaneously in subjects with active rheumatoid arthritis (RA) despite methotrexate therapy. In Part A, approximately 40 subjects were randomly assigned in a 1:1 fashion to receive either sirukumab 100 mg or placebo subcutaneous (SC) injections at week 0 and every 2 weeks thereafter through week 10. At week 12, subjects randomized to sirukumab began receiving placebo and subjects randomized to placebo began receiving sirukumab 100 mg SC injections every 2 weeks through week 22. An interim analysis was performed when all subjects randomized in Part A had either completed the week 12 visit or terminated study participation. Based on the results from this interim analysis, Part B has been initiated.
About Sirukumab (CNTO 136)
Sirukumab is a human monoclonal IgG1 kappa antibody in development for the treatment of active rheumatoid arthritis (RA). Sirukumab targets the cytokine interleukin (IL)-6, a naturally occurring protein that is believed to play a role in autoimmune conditions like RA. Sirukumab is also being investigated as a treatment for lupus nephritis and is currently in Phase 2 study.
About Centocor Ortho Biotech Inc.
Centocor Ortho Biotech Inc. redefines the standard of care in immunology, nephrology, and oncology. Built upon a pioneering history, Centocor Ortho Biotech harnesses innovations in large-molecule and small-molecule research to create important new therapeutic options. Beyond its innovative medicines, Centocor Ortho Biotech is at the forefront of developing education and public policy initiatives to ensure patients and their families, caregivers, advocates, and healthcare professionals have access to the latest treatment information, support services, and quality care. For more information about Centocor Ortho Biotech, visit www.CentocorOrthoBiotech.com.
 Centers for Disease Control and Prevention. Arthritis-Related Statistics. Available at: http://www.cdc.gov/arthritis/data_statistics/arthritis_related_stats.htm. Accessed April 7, 2011.
 World Health Organization. The global burden of disease: 2004 update. Geneva: WHO Press, 2008. Available at: http://www.who.int/healthinfo/global_burden_disease/GBD_report_2004update_full.pdf. Accessed April 13, 2011.
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Johnson & Johnson
Centocor Ortho Biotech Inc.