New Phase 2 Data Show Stelara® (ustekinumab) Sustained Improvement in Disease Activity in Adults With Systemic Lupus Erythematosus Through One Year

BEERSE, Belgium, October 23, 2018 /PRNewswire/ --

• Janssen presents one-year data from continued Phase 2 lupus study during plenary session at 2018 American College of Rheumatology (ACR) / Association for Rheumatology Health Professionals (ARHP) Annual Meeting     

The Janssen Pharmaceutical Companies of Johnson & Johnson today announced results through one year of a randomised, placebo-controlled Phase 2 study investigating STELARA^®* (ustekinumab) in the treatment of active systemic lupus erythematosus (SLE or lupus). The data show sustained improvements across global and organ-specific disease activity measures in patients receiving ustekinumab continuously through one year, and improvements in patients who crossed over from placebo to ustekinumab at week 24 through one year.^[1] The data are being presented at a plenary session during the American College of Rheumatology and Association of Rheumatology Health Professionals (ACR / ARHP) 2018 Annual Meeting taking place 19-24 October.

"Lupus, a chronic autoimmune disease, can affect the joints, skin, heart, lungs, kidneys and brain. For those who live with it, it can be debilitating and even life-threatening," 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 results of this longer-term Phase 2 study further support the role that IL-12 and -23 cytokines may play in the pathophysiology of the disease and underscore the need for additional treatment options for patients living with lupus."

The one-year results build on initial data from the Phase 2 trial, which found a significantly higher proportion of patients receiving ustekinumab showed improvements in lupus disease activity, as measured by the SLE Responder Index (SRI)-4 response, at week 24, compared with placebo (62% vs. 33% respectively, P=0.0057). These findings were presented at the ACR / ARHP 2017 Annual Meeting and were recently published online (September) and in the October print issue of The Lancet.^[1]

After the 24-week placebo-controlled period of the study, patients receiving placebo crossed over to receive ustekinumab (90 mg SC every 8 weeks), while patients receiving ustekinumab continued to receive ustekinumab at the same dose (90 mg SC every 8 weeks). Following 48 weeks (or approximately one year) of treatment, data showed the following:^[1]

• Of patients initially randomised to ustekinumab:
  • 63% of patients met SRI-4 response criteria.
  • Rates of changes from baseline in SLE Disease Activity-2K (SLEDAI-2K) were sustained from week 24 (65%) through one year (67%).
  • Rates of Physician Global Assessment (PGA) and active joint responses were sustained from week 24 to one year.
  • Response rate of Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) increased from week 24 (53%) through one year (69%).
• Of placebo-controlled patients who crossed over to ustekinumab at week 24, 55% achieved an SRI-4 response at one year.

Safety was assessed through week 56. Of patients who continued on ustekinumab or crossed over from placebo to ustekinumab, 15% had serious adverse events (SAEs) and 7.5% had serious infections through week 56. No deaths, malignancies, opportunistic infections or tuberculosis cases were observed. Safety events were consistent with the known ustekinumab safety profile.

"Our commitment to innovating on behalf of people with chronic immune diseases is 20 years strong and remains steadfast as we expand our work to help more people in need, including those with lupus," said Jaime Oliver Vigueras, Europe, Middle East and Africa Immunology Therapeutic Area Lead, Janssen-Cilag AG. "It's a truly exciting time as these latest findings serve as a catalyst as we advance the programme into Phase 3."

Based on the results of the Phase 2 study, Janssen has initiated the Phase 3 LOTUS study (NCT no. NCT03517722 / EudraCT no. 2017-001489-53). Janssen will collaborate with the Lupus Foundation of America (LFA) to incorporate the Rapid Evaluation of Activity in Lupus (LFA-REAL™) instrument into the Phase 3 study. LFA-REAL was developed by the LFA as a disease monitoring tool for use in clinical trials and clinical practice. An important feature of the LFA-REAL is that it integrates both clinician and patient input to determine the impact of SLE on the health and daily life of patients. Additionally, Janssen will work with the Lupus Research Alliance (LRA) and its network of leading lupus experts within the Lupus Clinical Investigators Network (LuCIN), to provide a coordinated framework to accelerate the development of ustekinumab for the treatment of lupus.

"With such a limited amount of treatment options available for patients with lupus, there is a great need for those living with the disease to have the possibility of additional therapies," said Kenneth Farber, President and Chief Executive Officer at Lupus Research Alliance. "We look forward to continuing collaborations with Janssen in the Phase 3 study to further evaluate ustekinumab as a potential treatment option."

About the Phase 2 ustekinumab SLE Trial^[1]   
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. Modified intention-to-treat (mITT) analyses across SLE disease activity measures were performed to evaluate maintenance of response with ustekinumab between week 24 and week 48. Safety was assessed through week 56.

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 British Isles Lupus Assessment Group (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 BILAG-Based Composite Lupus Assessment (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 inputted as non-responders. Long-term safety and efficacy data are currently being collected through 104 weeks.

About systemic lupus erythematosus (SLE)      
Lupus is a chronic, inflammatory autoimmune disease that can affect many different body systems, including joints, skin, heart, lungs, kidneys and brain.^[2] SLE can range from mild to severe and is characterised by inflammation of any organ system and complex auto-antibody production (antibodies directed against normal human tissue).^[3] The disease most often affects women and disproportionately affects women of African American, Hispanic, Asian and Native American descent compared to Caucasian women.^[4] Incidence rates vary across European countries, ranging from 2.2 cases/100,000 in Spain to 5 cases/100,000 in France.^[5] Lupus is estimated to affect at least 5 million people worldwide.^[6]

About ustekinumab^[7]     
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.^[7] 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.^[7] Ustekinumab is approved by the European Commission 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.^[7]

*Ustekinumab is currently under investigation and is not approved for SLE. A Phase 3 programme evaluating ustekinumab in the treatment of adults with active SLE is ongoing.

The common (≥1/100) adverse reactions reported in controlled periods of the adult psoriasis, psoriatic arthritis and Crohn's disease clinical studies with ustekinumab as well as post-marketing experience were: upper respiratory tract infection, arthralgia, back pain, diarrhoea, dizziness, fatigue, headache, injection site pain, injection site erythema, myalgia, nasopharyngitis, nausea, oropharyngeal pain, pruritus and vomiting.^[7]

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 90 countries, paediatric psoriasis in 43 countries, psoriatic arthritis in 83 countries and Crohn's disease in 62 countries.

STELARA^® (ustekinumab) is a registered trademark of Johnson & Johnson.

Important Safety Information 
For complete European Union (EU) prescribing information, please visit: www.ema.europa.eu/documents/product-information/stelara-epar-product-information_en.pdf.

About the Janssen Pharmaceutical Companies of Johnson & Johnson 
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 www.twitter.com/JanssenEMEA. Janssen-Cilag International NV, marketing authorisation holder for ustekinumab in the European Union, and Janssen-Cilag AG are part of the Janssen Pharmaceutical Companies of Johnson & Johnson.

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 study data on ustekinumab in Europe. 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 materialise, actual results could vary materially from the expectations and projections of Janssen-Cilag International NV, any of the other Janssen Pharmaceutical Companies 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; uncertainty of commercial success; manufacturing difficulties or delays; 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 behaviour 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 December 31, 2017, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors," in the company's most recently filed Quarterly Report on Form 10-Q and in 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. Neither of 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. 

**Dr. van Vollenhoven is a paid consultant for Janssen. He was not compensated for any media work.     

Date of preparation: October 2018 
PHGB/IMM/1018/0006    

1. Van Vollenhoven, R. F., et al (2018). Efficacy and Safety of Ustekinumab, an Interleukin-12/23 Inhibitor, in Patients with Active Systemic Lupus Erythematosus: 1-Year Results of a Phase 2, Randomized Placebo-Controlled, Crossover Study. 2018 American College of Rheumatology Annual Meeting, Abstract no. 2785. 

2. Mayo Clinic. Lupus. Available at: http://www.mayoclinic.org/diseases-conditions/lupus/symptoms-causes/syc-20365789. Accessed Oct 2018. 

3. Moulton, V. R., Suarez-Fueyo, A., Meidan, E., Li, H., Mizui, M., & Tsokos, G. C. Pathogenesis of human systemic lupus erythematosus: a cellular perspective. Trends in molecular medicine 2017;23(7), 615-635. 

4. Lupus Research Alliance. About Lupus. Available at: http://www.lupusresearch.org/understanding-lupus/what-is-lupus/about-lupus/. Accessed Oct 2018. 

5. Danchenko N, Satia JA and Anthony MS. Epidemiology of systemic lupus erythematosus: a comparison of worldwide disease burden. Lupus 2006;15:308-318. 

6. Lupus UK. World Lupus Day 2018 Survey Findings. Available at: http://www.lupusuk.org.uk/wld-survey-2018/. Accessed Oct 2018. 

7. EMC. STELARA 45 mg solution for injection (vials) SmPC. Available at: http://www.medicines.org.uk/emc/product/4413/smpc. Accessed Oct 2018.

SOURCE Janssen