Janssen announced 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).

"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.

The Lupus Research Alliance advocated for investigating STELARA in SLE given the limited treatment options and the high unmet medical need for patients.

Based on the results of the Phase 2 study results, Janssen plans to advance STELARA into a Phase 3 SLE development program in 2018.