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Janssen has announced positive results from a randomised, placebo-controlled Phase II 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 were 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, MD, PhD, 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 II 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 II study showing the potential of ustekinumab in the treatment of lupus,” said Newman Yeilding, MD, 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 III 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 II 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 II study results, Janssen plans to advance ustekinumab into a Phase III SLE development program in 2018.
