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Janssen Research & Development, LLC (Janssen) announced today positive results from a randomised, placebo-controlled Phase 2 study investigating the anti-interleukin (IL)-12/23 monoclonal antibody STELARA® (ustekinumab) in the treatment of active systemic lupus erythematosus (SLE or lupus). The study met the primary endpoint, with a significantly higher proportion of patients in the ustekinumab group showing improvements in lupus disease activity as measured by the SLE Responder Index (SRI)-4 response at week 24, compared with patients receiving placebo (60% vs. 31%, respectively, P=0.0046). The data are being presented as a late-breaking oral presentation at the 2017 ACR/ARHP Annual Meeting in San Diego.
"Despite the progress made in the treatment of autoimmune diseases, major unmet needs remain for patients living with lupus, a serious, life-altering and in some cases, life-threatening disease," said Ronald van Vollenhoven, M.D. Ph.D., Director of the Amsterdam Rheumatology and Immunology Center ARC and Professor of Rheumatology, University of Amsterdam and Free University; and lead study investigator. "The positive data from this Phase 2 study of ustekinumab are encouraging, highlighting the role that IL-12 and/or IL-23 may play in the pathophysiology of the disease, and offering hope for patients living with lupus and the rheumatology community."
Consistent with the primary endpoint, at week 24 patients receiving ustekinumab experienced significantly greater changes from baseline in Systemic Lupus Erythematosus Disease Activity-2K (SLEDAI-2K) score compared with patients receiving placebo (Least Squares Mean difference -1.36, P=0.09) at a predefined alpha level of 0.1 ustekinumab did not meet statistical significance in other secondary endpoints, although investigators reported a numerical trend favoring ustekinumab for such endpoints as Physician Global Assessment, British Isles Lupus Assessment Group (BILAG)-based Combined Lupus Assessment (BICLA) and BILAG, unique measures of disease activity in SLE. A pre-specified exploratory endpoint demonstrated that the risk of a new BILAG flare (at least one new BILAG A or at least two new BILAG B) was nominally significantly lower in the ustekinumab group compared with the placebo group (HR 0.11 [95% CI 0.01-0.94]; nominal P=0.0078).
Similar proportions of adverse events (AEs) across ustekinumab and placebo treatment groups were reported. Serious AEs occurred in 8.3% of patients receiving ustekinumab and 9.5% receiving placebo, with the most common adverse events including upper respiratory tract infection, urinary tract infection, nasopharyngitis and headache. Ustekinumab demonstrated a similar safety profile to previous trials for approved indications in moderate to severe plaque psoriasis, active psoriatic arthritis and moderately to severely active Crohn's disease. No deaths have been reported in the study to date.
"We are excited by the results from this Phase 2 study showing the potential of ustekinumab in the treatment of lupus," said Newman Yeilding, M.D., Head of Immunology Development, Janssen. "These findings, together with our knowledge of the IL-12/23 pathway and our commitment to transform the lives of patients with lupus, provide strong rationale for moving into a Phase 3 clinical development program."
The Lupus Research Alliance advocated for investigating ustekinumab in SLE given the limited treatment options and the high unmet medical need for patients.
"Lupus is a devastating autoimmune disease that affects the organs, joints and skin. Unfortunately for people living with the disease, effective treatment options to date are limited," said Kenneth Farber, President and Chief Executive Officer at Lupus Research Alliance. "In this Phase 2 study, ustekinumab showed clinical improvements in lupus disease activity and symptoms, which brings important hope to patients who have eagerly awaited new treatment options. We look forward to continuing to collaborate with Janssen on the important clinical program for ustekinumab in lupus."
Based on the results of the Phase 2 study results, Janssen plans to advance ustekinumab into a Phase 3 SLE development program in 2018.
About the Phase 2 ustekinumab SLE Trial
The efficacy and safety of ustekinumab was evaluated in a global Phase 2, randomised, placebo-controlled trial in 102 adults with seropositive SLE by Systemic Lupus International Collaborating Clinics (SLICC) criteria and active disease despite ongoing standard of care therapy (steroid, antimalarial and/or immunosuppressive therapies). Patients were randomised (3:2) to receive intravenous (IV) ustekinumab 6 mg/kg or placebo (PBO) at week 0, followed by subcutaneous (SC) injections of ustekinumab 90 mg or placebo every eight weeks, both in addition to standard of care therapy for 24 weeks. At week 24, patients in the placebo arm crossed over to active study agent.
The primary endpoint was the proportion of patients achieving SRI-4 response at week 24. The SRI combines scores from three different validated lupus disease indexes to define responders versus non-responders, and has previously been accepted by health authorities in SLE registration trials. To achieve SRI-4 response, an individual with lupus must have at least a four-point improvement on the SLEDAI-2K score, less than 10% increase in PGA of disease activity and no worsening of moderate/severe organ disease on the BILAG disease activity index. Major secondary endpoints included change from baseline in SLEDAI-2K score, change from baseline in PGA of disease activity, and proportion of patients with BICLA response, all at week 24. Joint and cutaneous disease activity were also assessed with joint counts and Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI), respectively.
Endpoint analyses included all patients who received at least one dose of study agent, had at least one measurement prior to administration, and had at least one post-baseline measurement. Patients with missing data and treatment failures were imputed as non-responders. Long-term safety and efficacy data are currently being collected through 104 weeks.
Lupus is a chronic, inflammatory autoimmune disease that can affect many different body systems, including joints, skin, heart, lungs, kidneys and brain. SLE can range from mild to severe and is characterised by inflammation of any organ system including kidneys, nervous system and brain. The disease most often affects women and disproportionately affects women of African American, Hispanic, Asian and Native American descent compared to Caucasian women. Incidence rates vary across European countries, ranging from 2.2 cases/100,000 in Spain to 5 cases/100,000 in France. Lupus is estimated to affect at least 5 million people worldwide.
In the European Union, ustekinumab is approved for the treatment of moderate to severe plaque psoriasis in adults who failed to respond to, or who have a contraindication to, or are intolerant to other systemic therapies including ciclosporin, methotrexate (MTX) or psoralen plus ultraviolet A (PUVA), and is also indicated for the treatment of moderate to severe plaque psoriasis in adolescent patients from the age of 12 years and older who are inadequately controlled by or are intolerant to other systemic therapies or phototherapies. In addition, ustekinumab is approved alone or in combination with MTX for the treatment of active psoriatic arthritis in adult patients when the response to previous non-biological disease-modifying antirheumatic drug (DMARD) therapy has been inadequate. In November 2016, the European Commission approved ustekinumab for the treatment of adult patients with moderately to severely active Crohn's disease who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a TNF-alpha antagonist or have medical contraindications to such therapies.
The Janssen Pharmaceutical Companies of Johnson & Johnson maintain exclusive worldwide marketing rights to ustekinumab, which is currently approved for the treatment of moderate to severe plaque psoriasis in 89 countries, paediatric psoriasis in 42 countries, psoriatic arthritis in 83 countries and Crohn's disease in 40 countries.
Important Safety Information
For complete European Union (EU) prescribing information, please visit: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000958/human_med_001065.jsp&mid=WC0b01ac058001d124
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 at https://twitter.com/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 the potential benefits and expectations for continued development of STELARA® (ustekinumab). 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/or 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; the uncertainty of commercial success; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; 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 1, 2017, including under "Item 1A. Risk Factors," its most recently filed Quarterly Report on Form 10-Q, including in the section captioned "Cautionary Note Regarding Forward-Looking Statements," and in the company's subsequent filings with the Securities and Exchange Commission. Copies of these filings are available online atwww.sec.gov,www.jnj.com or on request from Johnson & Johnson. Neither the Janssen Pharmaceutical Companies nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.
NHS Choices. Lupus. Available at:https://beta.nhs.uk/conditions/lupus/?WT.mc_id=organic_split. Accessed 31 October 2017.
Arthritis Research UK. Lupus (SLE). Available at:https://www.arthritisresearchuk.org/arthritis-information/conditions/lupus.aspx. Accessed 31 October 2017.
Lupus Research Alliance. About Lupus. Available at:http://www.lupusresearch.org/understanding-lupus/what-is-lupus/about-lupus/. Accessed 31 October 2017.
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Summary of Product Characteristics Stelara 45 mg solution. Janssen-Cilag International NV. Available at:http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000958/WC500058513.pdf. Accessed 31 October 2017.
PHEM/STE/1117/0001 November 2017
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