New Phase 3 Monotherapy Study of Sirukumab Versus Humira® and Sirukumab Data in an Anti-TNF Refractory Population Reported in the Treatment of Moderately to Severely Active Rheumatoid Arthritis

WASHINGTON, Nov. 16, 2016 /PRNewswire/ -- Janssen Research & Development, LLC (Janssen) announced today results from two pivotal Phase 3 studies evaluating subcutaneous (SC) sirukumab, a human anti-interleukin (IL)-6 monoclonal antibody in development for the treatment of adults with moderately to severely active rheumatoid arthritis (RA). Data from the Janssen-sponsored head-to-head study, SIRROUND-H, showed patients receiving sirukumab monotherapy demonstrated significantly greater improvement in Disease Activity Score (DAS28), the first of two co-primary endpoints, when compared with Humira^® (adalimumab) monotherapy. Investigators also reported results from a second study (SIRROUND-T), which showed that patients refractory to or intolerant to one or more anti-tumor necrosis factor (TNF) treatments receiving sirukumab demonstrated significant improvement in signs and symptoms of active RA compared with placebo. Sirukumab is currently being evaluated by health authorities in Europe, the U.S. and Japan as a SC therapy for the treatment of adult patients with moderately to severely active RA.

• In SIRROUND-H, a comparator study of sirukumab monotherapy versus adalimumab monotherapy, patients receiving sirukumab 50 mg every four weeks (q4w) and patients receiving sirukumab 100 mg every two weeks (q2w) experienced significant mean changes from baseline in DAS28 at week 24 of -2.58 and -2.96, respectively, one of two co-primary endpoints of the study, compared with a mean change of -2.19 in patients receiving adalimumab 40 mg q2w (P = 0.013 and P < 0.001, respectively). All treatment groups showed clinically relevant improvements in achieving the other co-primary endpoint, at least 50 percent improvement in signs and symptoms (ACR50) of disease at week 24, although the proportions of patients in ACR50 response were not significantly different between sirukumab 50 mg q4w, sirukumab 100 mg q2w and adalimumab 40 mg q2w (27 percent, 35 percent and 32 percent, respectively [P > 0.05]).
• In SIRROUND-T, among patients refractory/intolerant to anti-TNF treatments, 40 percent of patients receiving sirukumab 50 mg q4w and 45 percent of patients receiving sirukumab 100 mg q2w achieved the study's primary endpoint, at least a 20 percent improvement in signs and symptoms (ACR20) at week 16, compared with 24 percent of patients receiving placebo (P ≤ 0.001). Approximately 40 percent of patients in the study had prior exposure to non-TNF biologic therapies.

"We are focused on developing a range of therapeutic options to help meet the needs of people living with RA, including individuals who are still searching for an effective option having not experienced success with other advanced therapies," said Newman Yeilding, M.D., Head of Immunology Development, Janssen Research & Development, LLC. "We believe the sirukumab data generated to date show the potential of this IL-6-targeted therapy to benefit adults living with moderately to severely active RA in the future, and we look forward to continuing to work with global health authorities on the applications that have been submitted."

SIRROUND-H: Efficacy and Safety of Monotherapy with Sirukumab, an Anti-IL-6 Cytokine Monoclonal Antibody, Compared with Adalimumab Monotherapy in Biologic-Naïve Patients with Active Rheumatoid Arthritis
The Phase 3 SIRROUND-H trial is a randomized, double-blind, parallel-group study that included 559 biologic-naïve  patients with moderately to severely active RA who were intolerant to methotrexate (MTX), considered inappropriate for MTX treatment for safety reasons or were inadequate responders to MTX. Patients were randomized evenly to receive sirukumab 50 mg q4w or sirukumab 100 mg q2w or adalimumab 40 mg q2w as monotherapy. In addition to the co-primary endpoints evaluated, a clinically relevant proportion of patients in all three treatment groups attained the major secondary endpoints of low disease activity in 28 joints (DAS28 Remission; sirukumab 50 mg q4w, 13 percent; sirukumab 100 mg q2w, 20 percent; adalimumab, 8 percent [P = 0.086 and P < 0.001, respectively]) and ACR20 response at week 24 (sirukumab 50 mg q4w, 54 percent; sirukumab 100 mg q2w, 59 percent; adalimumab q2w 57 percent [P > 0.05]).

"We saw significant improvements in disease activity among patients receiving both doses of sirukumab compared with those receiving adalimumab, and while sirukumab-treated patients demonstrated clinically relevant ACR50 improvements, the difference in ACR50 response rates results did not reach statistical significance," said Peter Taylor, Ph.D., Norman Collisson Professor of Musculoskeletal Sciences, Kennedy Institute of Rheumatology, University of Oxford and lead SIRROUND-H investigator. "As not all patients are appropriate candidates for TNF blocker therapy or methotrexate, and many are intolerant of methotrexate, the clinical improvements observed with sirukumab in this study provide important insights when evaluating available data for this IL-6 inhibitor in the treatment of moderately to severely active rheumatoid arthritis."

The incidence of patients reporting adverse events (AEs) was 57 percent, 64 percent and 55 percent in the sirukumab 50 mg q4w, sirukumab 100 mg q2w and adalimumab q2w groups, respectively. The incidence of patients reporting serious AEs was 7 percent, 3 percent and 4 percent in the sirukumab 50 mg q4w, sirukumab 100 mg q2w and adalimumab q2w groups, respectively. The rate of reported infections was 20 percent, 24 percent and 19 percent in the sirukumab 50 mg q4w, sirukumab 100 mg q2w and adalimumab q2w groups, respectively, and there were few serious infections reported (sirukumab 50 mg q4w, 3 percent; sirukumab 100 mg q2w, 0 percent; adalimumab q2w, 1 percent). The reported incidence of injection-site reactions was dose-related and greater with sirukumab 100 mg q2w (21 percent) compared with sirukumab 50 mg q4w (11 percent) and adalimumab q2w (8 percent). No injection-site reactions were considered serious, and there were no deaths reported through week 24.

SIRROUND-T: Efficacy and Safety of Sirukumab, an Anti-IL-6 Cytokine Monoclonal Antibody, in Patients with Active Rheumatoid Arthritis Despite Anti-TNF and Other Biologic Therapy
The Phase 3 SIRROUND-T trial is a randomized, double-blind, placebo-controlled study that included 878 patients refractory to anti-TNF therapy, approximately 40 percent of whom had prior exposure to non-TNF biologic therapies. Patients were randomized evenly to receive sirukumab 50 mg q4w or sirukumab 100 mg q2w or placebo. Patients receiving placebo with less than 20 percent improvement from baseline in both swollen and tender joint counts at weeks 18, as well as those still on placebo at week 24, were re-randomized to receive SC injections of sirukumab 50 mg q4w or 100 mg q2w through week 52. In addition to meeting the primary endpoint, patients receiving sirukumab also demonstrated statistically significant improvements across secondary endpoints compared with placebo. These included a change from baseline in the Health Assessment Questionnaire Disability Index (HAQ-DI), percentage of patients achieving ACR50 and percentage of patients with low disease activity in 28 joints (DAS28 Remission) at week 24 (P ≤ 0.001 for all measures). These improvements were seen as early as week four and were maintained with sirukumab therapy through week 52. Additionally, the efficacy of sirukumab was similar in patients who had previously received both anti-TNF therapy and other biologic therapy and in patients who had taken only TNF inhibitors.

"These Phase 3 results—the first of an IL-6 cytokine inhibitor in RA—showed significant improvements in the signs and symptoms of patients with moderately to severely active RA whose disease remains active despite treatment with anti-TNF therapy, a typically difficult to treat group," said Daniel Aletaha, Consultant Physician, Division of Rheumatology, Medical University of Vienna and lead SIRROUND-T investigator. "Improvements in pain and inflammation were seen within four weeks and were maintained with sirukumab treatment through one year."

The incidence of patients reporting AEs was 66 percent, 71 percent and 62 percent in the sirukumab 50 mg q4w, sirukumab 100 mg q2w and placebo groups, respectively. Incidence of patients reporting serious AEs was 10 percent, 8 percent and 5 percent in the sirukumab 50 mg q4w, sirukumab100 mg q2w and placebo groups, respectively. Through week 52, the incidences of AEs and serious AEs were comparable between sirukumab 50 mg q4w (80 percent and 14 percent, respectively) and sirukumab 100 mg q2w (81 percent and 13 percent, respectively). No deaths were reported through week 24; there were five deaths reported through week 52 (two in the sirukumab 50 mg q4w group and three in the sirukumab 100 mg q2w group). 

About the SIRROUND Clinical Program
The Phase 3 clinical program in patients with active RA includes five studies investigating subcutaneously administered sirukumab 50 mg every four weeks and sirukumab 100 mg every two weeks in combination with conventional disease-modifying antirheumatic drugs (DMARDs) or as monotherapy. The comprehensive development program involves more than 3,000 patients encompassing the following five studies:

• SIRROUND-D study: patients who had an inadequate response to DMARDs. This study is estimated to complete in 2017.
• SIRROUND-H study: patients with an inadequate response or who were intolerant to MTX or for whom MTX was inappropriate. This study has completed.
• SIRROUND-T study: patients who had an inadequate response or were intolerant to anti-TNF-alpha agents. This study has completed.
• SIRROUND-M study: Japanese patients who had an inadequate response to MTX or sulfasalazine. This study has completed.
• SIRROUND-LTE study: a long-term extension study for patients completing SIRROUND-D and SIRROUND-T. This study is estimated to complete in 2020.

About Sirukumab
Sirukumab is a human monoclonal IgG1 kappa antibody that targets the cytokine IL-6, a naturally occurring protein that is believed to play a role in autoimmune conditions like RA. It is not approved as a treatment for RA or any other indication anywhere in the world.

In December 2011, Janssen and GSK entered into a licensing and co-development agreement with respect to sirukumab. Under the terms, Janssen retains exclusive rights to commercialize sirukumab in Europe, the Middle East, Africa and Asia Pacific, while GSK has commercialization rights in North, Central and South America. The agreement gives both companies the option to investigate sirukumab for other indications beyond RA. Sirukumab is currently being evaluated by health authorities in Europe, the U.S. and Japan as a SC therapy for the treatment of adult patients with moderately to severely active RA.

About Rheumatoid Arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory condition that is characterized by pain, joint swelling, stiffness, joint destruction and disability. It is estimated that more than 23.5 million people worldwide are affected by the condition, for which there is no cure.[1]

About the Janssen Pharmaceutical Companies
At the Janssen Pharmaceutical Companies of Johnson & Johnson, we are working to create a world without disease. Transforming lives by finding new and better ways to prevent, intercept, treat and cure disease inspires us. We bring together the best minds and pursue the most promising science. We are Janssen. We collaborate with the world for the health of everyone in it. Learn more at www.janssen.com. Follow us at Twitter.com/JanssenGlobal.

Cautions Concerning Forward-Looking Statements
This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding new product development including ongoing clinical studies. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC and Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; competition, including technological advances, new products and patents attained by competitors; challenges to patents; manufacturing difficulties or delays; product efficacy or safety concerns resulting in product recalls or regulatory action; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended January 3, 2016, including in Exhibit 99 thereto, and the company's subsequent filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. None of the Janssen Pharmaceutical Companies or Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.

Humira^® is a registered trademark of AbbVie Inc.

[1] Centers for Disease Control and Prevention. Rheumatoid Arthritis (RA). Available at: http://www.cdc.gov/arthritis/basics/rheumatoid.htm. Accessed August 16, 2016.

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