STELARA® (ustekinumab) Shows Positive Results In Treatment Of Systemic Lupus Erythematosus In Phase 2 Trial

- 60 percent of patients receiving STELARA® showed significant reductions in lupus disease activity vs. 31 percent of patients receiving placebo

- STELARA® showed significant improvements in various disease measures compared with placebo, including musculoskeletal, mucocutaneous, immunological markers and flares

- Janssen plans to advance STELARA® into Phase 3 development program based on Phase 2 results

SAN DIEGO, CA, USA I November 6, 2017 I Janssen Research & Development, LLC (Janssen) announced today positive results from a randomized, 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 STELARA® 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 percent vs. 31 percent, 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 STELARA® experienced significantly greater changes from baseline in SLE 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. STELARA® did not meet statistical significance in other secondary endpoints, although investigators reported a numerical trend favoring STELARA® 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 STELARA® group compared with the placebo group (HR 0.11 [95 percent CI 0.01-0.94]; nominal P=0.0078).

Similar proportions of adverse events (AEs) across STELARA® and placebo treatment groups were reported. Serious AEs occurred in 8.3 percent of patients receiving STELARA® and 9.5 percent receiving placebo. STELARA® 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 STELARA® 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 STELARA® 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 STELARA® into a Phase 3 SLE development program in 2018.

About the Phase 2 STELARA® SLE Trial
The efficacy and safety of ustekinumab (UST) was evaluated in a global Phase 2, randomized, 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 randomized (3:2) to receive intravenous (IV) STELARA® 6 mg/kg or placebo (PBO) at week 0, followed by subcutaneous (SC) injections of STELARA® 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 percent 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.

About SLE
Lupus is a chronic, inflammatory autoimmune disorder that can affect many different body systems, including joints, skin, heart, lungs, kidneys and brain.1 SLE, the most common form of lupus, can range from mild to severe and is characterized by inflammation of any organ system including kidneys, nervous system, brain or brain vasculature, as well as potential hardening of the arteries or coronary artery disease.2 The disease most often affects women and disproportionately affects women of African American, Hispanic, Asian and Native American descent compared to Caucasian women.3 Lupus is estimated to affect at least 1.5 million Americans and 5 million people worldwide.4

About STELARA® (ustekinumab)
STELARA®, a fully human interleukin (IL)-12 and IL-23 antagonist, is a prescription medicine used to treat adults and adolescents 12 years of age and older with moderate or severe plaque psoriasis who are candidates for phototherapy or systemic therapy.

STELARA® is also indicated for the treatment of adult patients 18 years and older with active psoriatic arthritis, alone or in combination with methotrexate, and for the treatment of adult patients 18 years or older with moderately to severely active Crohn's disease. STELARA® is in Phase 2 development for the treatment of systemic lupus erythematosus, however, safety and efficacy in the treatment of patients with SLE has not been established and STELARA® is not approved for this indication.

The Janssen Pharmaceutical Companies of Johnson & Johnson maintain exclusive worldwide marketing rights to STELARA®.

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 on Twitter at https://twitter.com/JanssenGlobal.

References
1 Mayo Clinic. Lupus. Available at: http://www.mayoclinic.org/diseases-conditions/lupus/basics/definition/con-20019676. Accessed October 9, 2017.
2 Lupus Foundation of America. Different Types of Lupus. Available at https://resources.lupus.org/entry/types-of-lupus. Accessed October 9, 2017.
3 Lupus Research Alliance. About Lupus. Available at http://www.lupusresearch.org/understanding-lupus/what-is-lupus/about-lupus/. Accessed October 9, 2017.
4 Lupus Foundation of America. What is Lupus? Available at https://resources.lupus.org/entry/what-is-lupus?utm_source=lupusorg&utm_medium=answersFAQ. Accessed October 9, 2017.

SOURCE: Janssen Pharmaceutical

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