New Janssen Phase 3 Data in Patients with Moderately to Severely Active Rheumatoid Arthritis Shows Sirukumab Significantly Inhibited Radiographic Progression and Improves Signs and Symptoms of Disease

Sirukumab One-year Radiographic Data Show Significant Inhibition of Joint Destruction.

London, United Kingdom, 8 June, 2016 – Janssen Research & Development, LLC (Janssen) announced today results from a pivotal Phase 3 study evaluating subcutaneous sirukumab (CNTO 136), 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 trial of 1,670 patients showed those receiving sirukumab demonstrated significant inhibition of radiographic progression, or joint destruction, from baseline to week 52 and improvement in signs and symptoms of RA at week 16, the study’s co-primary endpoints, when compared with patients receiving placebo.[i] Sirukumab is being co-developed as part of a collaboration with GSK. This data is scheduled for presentation during the Annual European Congress of Rheumatology (EULAR 2016).

The SIRROUND-D study met both co-primary endpoints evaluating treatment with sirukumab in adult patients with active RA who had an inadequate response to treatment with disease-modifying antirheumatic drugs (DMARDs):

• Inhibition of radiographic progression, or joint destruction, was significantly greater among sirukumab-treated patients, with a mean change from baseline to week 52 in the van der Heijde-Sharp score of 0.50 among patients receiving sirukumab 50 mg every four weeks (n=557) and 0.46 for patients receiving sirukumab 100 mg every two weeks (n=557) compared with 3.69 among the placebo group (n=556) (both P £001). ¹The van der Heijde-Sharp scoring method is an X-ray measure of changes in joint destruction and damage, including joint erosion and joint space narrowing. With this method, higher scores indicate greater structural damage while lower scores indicate less structural damage.
• Significant inhibition of radiographic progression was demonstrated in both patients naïve to biologic therapy and those treated with biologics in the past, and was seen as early as week 24.[ii]
• At least a 20 percent improvement in RA signs and symptoms as measured by the American College of Rheumatology (ACR20) at week 16 was achieved by 54.8 percent and 53.5 percent of patients receiving sirukumab 50 mg and sirukumab 100 mg, respectively, compared with 26.4 percent of the placebo group (both P £001).¹

“The results from this Phase 3 study showed significant inhibition of the progression of joint damage for sirukumab and improvements in the pain and inflammation patients with rheumatoid arthritis experience when not adequately controlled with traditional disease-modifying agents. Treatments that may allow us to limit the disease from causing permanent joint damage are valuable in the long-term management of rheumatoid arthritis,” said Tsutomu Takeuchi, Professor of Medicine, Division of Rheumatology and Clinical Immunology, Keio University School of Medicine, Tokyo, Japan. “We look forward to forthcoming data from ongoing Phase 3 programs to better understand the efficacy and safety of sirukumab in a broader and more diverse rheumatoid arthritis patient population.”

All major secondary endpoints were also met with statistical significance for both doses of sirukumab versus placebo (P £ 0.001 for all measures across both doses). These were the change from baseline in the health assessment questionnaire disability index (HAQ-DI), percentage of patients achieving at least a 50 percent improvement in RA symptoms (ACR50), percentage of patients with improved disease activity score in 28 joints (DAS28 Remission [DAS28 (CRP) <2.6]) at week 24, and percentage of patients achieving at least a 70 percent improvement in RA signs and symptoms (ACR70) for six consecutive months (major clinical response) by week 52.^1,3 Mean improvements in HAQ-DI scores were -0.43 for the sirukumab 50 mg group, -0.46 for the sirukumab 100 mg group and -0.22 for the placebo group. ACR50 was achieved by 30 and 33 percent of patients receiving sirukumab 50 mg and 100 mg, respectively, compared with 12 percent of placebo patients. DAS28 remission was achieved by 26 percent of patients in both sirukumab groups compared with 6 percent of patients in the placebo group.¹ Major clinical response was seen in 5 percent and 9 percent of patients receiving sirukumab 50 mg and 100 mg, compared with 2 percent of patients receiving placebo.¹

In the 18-week control period, the proportion of patients experiencing adverse events (AEs) and serious AEs, respectively, was higher with sirukumab 50 mg (79.6 percent and 11.0 percent) and sirukumab 100 mg (80.2 percent and 9.8 percent) versus placebo (65.5 percent and 6.8 percent), with the most common AEs being (at least 8 percent) elevated liver enzymes, upper respiratory tract infection, injection site erythema and nasopharyngitis.¹Through week 52, types of AEs and SAEs were similar.¹ Prior to week 18, the formal placebo-controlled period, three subjects died, one in each treatment group (placebo, sirukumab 50 mg and sirukumab 100 mg). From week 18 to week 52, there were 8 additional deaths: three in the group originally on placebo that switched to sirukumab 50 mg, three in the sirukumab 50 mg and two in the sirukumab 100 mg. Long-term safety and efficacy data are currently being collected in ongoing extensions of the three Phase 3 trials.¹

“Janssen is committed to advancing therapeutic options for people living with RA and for rheumatologists,” said Newman Yeilding, M.D., Head of Immunology Development, Janssen Research & Development, LLC. “We believe sirukumab represents an important investigational treatment option for the rheumatology community and we look forward to presenting additional data from the comprehensive Phase 3 development program in the future as we work towards global regulatory submissions this year.”

About SIRROUND-D
SIRROUND-D (CNTO136ARA3002) is a multicenter, randomized, double-blind, placebo-controlled, parallel group study in patients with moderately to severely active RA who had an inadequate response to disease-modifying antirheumatic drugs (DMARDs). The primary objective was to assess the efficacy of subcutaneous sirukumab as measured by the reduction of the signs and symptoms of RA and inhibition of radiographic progression. A total of 1,670 patients were randomized evenly to receive sirukumab 50 mg every 4 weeks or sirukumab 100 mg every 2 weeks or placebo.[iii]

The Phase 3 clinical program in patients with active RA also includes four other studies investigating sirukumab 50 mg and 100 mg administered subcutaneously in combination with conventional DMARDs or as monotherapy every four or two weeks, respectively. The comprehensive development program involves more than 3,000 patients, the largest RA trial program investigating an anti-IL-6 biologic therapy.^{3,[iv],[v],[vi],[vii]}

These other studies include patients with an inadequate response to anti-TNF agents and other biologic agents (SIRROUND-T study which has completed)⁴; patients with an inadequate response or were intolerant to methotrexate (MTX) or for whom MTX was inappropriate (SIRROUND-H study which is estimated to complete in September 2016)⁵; Japanese patients who had an inadequate response to MTX or sulfasalazine (SIRROUND-M study which has completed)⁶; and a long-term extension study for patients completing SIRROUND-D and SIRROUND-T (SIRROUND-LTE study which is estimated to complete in 2020).⁷

Information for Editors:

About Sirukumab
Sirukumab is an investigational human monoclonal IgG1 kappa antibody in Phase 3 development for the treatment of moderately to severely active RA.[viii] It is not approved as a treatment for RA or any other indication anywhere in the world.  Sirukumab targets the cytokine IL-6, a naturally occurring protein that is believed to play a role in autoimmune conditions like RA.[ix]

In December 2011, Janssen and GSK entered into a licensing and co-development agreement with respect to sirukumab. Under the terms, GSK has exclusive rights to commercialize sirukumab in North, Central and South America, while Janssen retains commercialization rights in the rest of the world, including such territories as EMEA and Asia Pacific. Prior to the agreement, Janssen had been developing sirukumab for RA.

As part of the collaboration, a Phase 3 Program began in August 2012 to investigate sirukumab for the treatment of moderately to severely active RA. The agreement gives both companies the option to investigate sirukumab for other indications beyond RA.

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

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/EMEA. Follow us on Twitter: @JanssenEMEA.

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 anticipated regulatory submissions. 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.

References

1. Takeuchi T, Thorne C, Karpouzas G et al. Efficacy and safety of sirukumab in patients with active rheumatoid arthritis despite disease-modifying anti-rheumatic drug treatment: Results of a randomized, double-blind, placebo-controlled study. Annual European Congress of Rheumatology (EULAR 2016); 8–10 June, 2016; London, UK; SAT0145.
2. Thorne C, Karpouzas G, Takeuchi T et al. Response and radiographic progression in biologic-naïve and biologic-experienced patients with rheumatoid arthritis treated with sirukumab. Annual European Congress of Rheumatology (EULAR 2016); 8–10 June, 2016; London, UK; SAT0158.
3. ClinicalTrials.gov. NCT01604343. Available at https://clinicaltrials.gov/ct2/show/NCT01604343 (last accessed June 2016).
4. ClinicalTrials.gov. NCT01606761. Available at https://clinicaltrials.gov/ct2/show/NCT01606761 (last accessed June 2016).
5. ClinicalTrials.gov. NCT02019472. Available at https://clinicaltrials.gov/ct2/show/NCT02019472 (last accessed June 2016).
6. ClinicalTrials.gov. NCT01689532. Available at https://clinicaltrials.gov/ct2/show/NCT01689532 (last accessed June 2016).
7. ClinicalTrials.gov. NCT01856309. Available at https://clinicaltrials.gov/ct2/show/NCT01856309 (last accessed June 2016).
8. Smolen J et al. Sirukumab, a human anti-interleukin-6 monoclonal antibody: a randomised, 2-part (proof-of-concept and dose-finding), phase II study in patients with active rheumatoid arthritis despite methotrexate therapy. Ann Rheum Dis 2014;73:1616–1625.
9. Rossi J et al. Interleukin-6 as a Therapeutic Target. Clin Can Res 2015;21(6):1248–1257.
10. World Health Organization. Chronic rheumatic conditions. Available at http://www.who.int/chp/topics/rheumatic/en (last accessed June 2016).
11. World Health Organization. The global burden of disease: 2004 update. Available at   http://www.who.int/healthinfo/global_burden_disease/GBD_report_2004update_full.pdf?ua=1 (last accessed June 2016).

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