Chicago, IL (November 7, 2011) – Results from Part B of a two-part Phase 2 study of sirukumab (CNTO 136), a subcutaneously administered human antibody directed against the cytokine interleukin (IL)-6, showed that patients with active rheumatoid arthritis (RA) receiving the monoclonal antibody demonstrated substantial improvement in signs and symptoms and inflammation. Findings from the proof-of-concept, dose-finding study of patients with active RA despite methotrexate therapy will be presented at the 2011 American College of Rheumatology Annual Scientific Meeting and follow positive Part A study results previously presented in June.
Treatment with sirukumab significantly improved arthritis signs and symptoms as measured by the American College of Rheumatology 50 (ACR50) response at week 12, the primary endpoint of the study, with 24 percent of patients in ACR50 response in the combined sirukumab group (inclusive of dose regimens: 100 mg every 2 weeks; 100 mg every 4 weeks; 50 mg every 4 weeks; 25 mg every 4 weeks) compared with 3 percent of patients receiving placebo plus methotrexate (P = 0.010). A higher proportion of patients achieved an ACR50 response in each of the four sirukumab groups with the 100 mg every 2 weeks and the 50 mg every 4 weeks groups reaching statistical significance at week 12 compared with the placebo group: 27 percent 100 mg every 2 weeks (P = 0.026); 23 percent 100 mg every 4 weeks (P = 0.052); 27 percent 50 mg every 4 weeks (P = 0.026) and 19 percent 25 mg every 4 weeks (P = 0.104).
At week 24, patients in the sirukumab treatment groups showed continued improvement in ACR50 response: 60 percent with 100 mg every 2 weeks; 50 percent with 100 mg every 4 weeks; 30 percent with 50 mg every 4 weeks and 36 percent with 25 mg every 4 weeks.
“The data show response across multiple dose regimens in a proof-of-concept study, with data at week 24 showing continued improvement in ACR50 scores,” said lead investigator Josef Smolen, M.D., Professor of Medicine, Department of Medicine at the Medical University of Vienna, Austria. “Thus, IL-6 remains a promising target for treating patients with RA, who frequently still struggle with their disease, and for rheumatologists. We look forward to additional sirukumab data to more thoroughly understand its potential in the treatment of rheumatoid arthritis.”
Investigators also reported at week 12 a greater average improvement from baseline in Disease Activity Score (DAS) 28 C-reactive protein (CRP) measure in each of the four sirukumab groups compared with the placebo group (P < 0.001). The mean levels of CRP observed in patients’ blood serum also decreased on average more than 80 percent across the four sirukumab dose regimens at week 2, and continued to remain suppressed through week 24. CRP is a type of protein produced in the liver and expressed during episodes of acute inflammation associated with RA.
In separate analyses, higher remission rates according to the 2011 ACR/European League Against Rheumatism (EULAR) Boolean and Simplified Disease Activity Index (SDAI) remission criteria and DAS28 CRP were achieved with sirukumab across the four dosing regimens compared with the placebo group, and increased to a peak at week 24 in the sirukumab 100 mg every-2-week and every-4-week treatment groups. Researchers also reported results of a subanalysis of the Phase 2 trial that correlated an effect of sirukumab therapy on hepcidin levels (a hormone shown to regulate iron levels in the blood) and markers of anemia. Serum hemoglobin levels in anemic patients increased significantly following sirukumab treatment, with half of the patients normalizing hemoglobin levels.
Treatment with sirukumab was generally well-tolerated. Overall there was no clear difference in safety among the four sirukumab dose regimens. Through week 38, adverse events (AEs) occurred more often with sirukumab than with placebo (81 percent vs. 67 percent), including mostly minor infections/infestations (31 percent vs. 13 percent), gastrointestinal disorders (19 percent vs. 10 percent) and injection site reactions (16 percent vs. 3 percent). Serious AEs were reported in 13 percent of patients receiving placebo and 9 percent of patients receiving sirukumab and the majority were infections. One patient died of brain aneurysm considered not related to study medication. Decreases in white blood cells, neutrophils, platelets and lymphocytes, as well as transaminase elevations, were observed after sirukumab treatment. Sustained increases from baseline starting at week 2 in total cholesterol (mean sirukumab vs. placebo: 19 percent ± 17 percent vs. -5 percent ± 12 percent) and low-density lipoprotein (LDL) (20 percent ± 20 percent vs. -4 percent ± 22 percent) were seen with sirukumab. These lab abnormalities occurred without dose relationship or short-term clinical sequelae. Antibodies to sirukumab were detectable through week 38 in 3 percent of evaluable patients; 3 of these patients were ACR50 responders at week 24 and none had injection site reactions.
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 Americans[1] and more than 23.5 million people worldwide[2] 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 RA despite methotrexate therapy. Results from Part A of the study were presented at EULAR in June. In Part B, 151 patients with active RA despite methotrexate therapy were continued on stable weekly methotrexate, and randomized equally to: (1) placebo every 2 weeks through week 10, and then sirukumab 100 mg subcutaneous (SC) injections every 2 weeks through week 24; (2) sirukumab 100 mg SC injections every 2 weeks through week 24; (3) sirukumab 100 mg SC injections every 4 weeks through week 24; (4) sirukumab 50 mg SC injections every 4 weeks through week 24; or (5) sirukumab 25 mg SC injections every 4 weeks through week 24. An analysis of the results was performed when all subjects had either completed the 38-week study or terminated study participation.
About Sirukumab (CNTO 136)
Sirukumab is an investigational human monoclonal IgG1 kappa antibody in development for the treatment of active 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 Janssen Biotech, Inc.
Janssen Biotech, Inc. redefines the standard of care in immunology, oncology, urology and nephrology. Built upon a rich legacy of innovative firsts, Janssen Biotech has delivered on the promise of new treatments and ways to improve the health of individuals with serious disease. Beyond its innovative medicines, Janssen Biotech is at the forefront of developing education and public policy initiatives to ensure patients and their families, caregivers, advocates and health care professionals have access to the latest treatment information, support services and quality care. For more information on Janssen Biotech, Inc. or its products, visit www.janssenbiotech.com.
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[1] Centers for Disease Control and Prevention. Arthritis-Related Statistics. http://www.cdc.gov/arthritis/data_statistics/arthritis_related_stats.htm. Accessed April 7, 2011.
[2] World Health Organization. The global burden of disease: 2004 update. Geneva: WHO Press, 2008. http://www.who.int/healthinfo/global_burden_disease/GBD_report_2004update_full.pdf. Accessed April 13, 2011.