A phase 2, randomised, placebo-controlled clinical trial of blisibimod, an inhibitor of B cell activating factor, in patients with moderate-to-severe systemic lupus erythematosus, the PEARL-SC study

Objective To evaluate the efficacy and safety of subcutaneous blisibimod, an inhibitor of B cell activating factor, in patients with systemic lupus erythematosus (SLE) in a dose-ranging Phase 2b clinical trial. Methods 547 patients with SLE with anti-double stranded DNA or antinuclear antibodies and Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) score >= 6 at baseline were randomised to receive placebo or blisibimod at one of 3 dose levels. The primary end point, measured at Week 24, was the SLE Responder Index-5 (SRI-5, meeting established SRI criteria but with >= 5 point improvement in SELENA-SLEDAI). Results Although SRI-5 response rates were not significantly improved in the pooled blisibimod groups compared with placebo, they were higher in subjects randomised to the highest dose of blisibimod (200 mg once-weekly (QW)) compared with pooled placebo, from Week 16 to Week 24, reaching statistical significance at Week 20 (p= 0.02). SRI response rates compared with placebo were higher still in subjects who attained SELENA-SLEDAI improvements of >= 8, and in a subgroup of patients with severe disease (SELENA-SLEDAI >= 10 and receiving corticosteroids at baseline). In subjects with protein: creatine ratios of 1-6 at baseline, significant reductions in proteinuria were observed with blisibimod. Significant (p< 0.01) changes in anti-double stranded DNA antibodies, complement C3 and C4, and reductions in B cells were observed with blisibimod. No imbalances in serious adverse events or infections (4/280 and 3/266), deaths (4/280 and 3/266) and malignancies (2/280 and 2/266) were reported for blisibimod compared with placebo. Conclusions This study successfully identified a safe, effective and convenient dose, study population and end point for evaluation of blisibimod effect in Phase 3.