Efficacy and Safety of Epratuzumab in Moderately to Severely Active Systemic Lupus Erythematosus: Results from the Phase 3, Randomized, Double-blind, Placebo-controlled Trials, EMBODY™ 1 and EMBODY™ 2.

Objective Epratuzumab, a monoclonal antibody that targets CD22, modulates B cell signaling without substantial reductions in B cells. We report data from two Phase 3, randomized, double-blind, placebo-controlled studies of epratuzumab in patients with moderately to severely active SLE; EMBODY 1 (NCT01262365) and EMBODY 2 (NCT01261793). Methods Patients met ≥4 ACR revised criteria, were ANA and/or anti-dsDNA positive, had SLEDAI-2K score ≥6, BILAG-2004 ≥1 A or ≥2 Bs in mucocutaneous, musculoskeletal or cardiorespiratory domains, and were receiving standard therapy (ST) including mandatory corticosteroids (5–60 mg/day). BILAG A grade renal and central nervous system domain scores were excluded. Patients were randomized 1:1:1 to placebo, epratuzumab 600 mg every week (QW) or 1200 mg every other week (QOW), with infusions delivered for the first 4 weeks of each 12-week dosing cycle, for 4 cycles. Patients across all three dosing arms continued their ST. The primary endpoint was the Week 48 response rate according to the BICLA definition, requiring BILAG improvement, no worsening in BILAG, SLEDAI-2K score and PhGA, with no disallowed changes in concomitant medications. Patients who discontinued were classified as non-responders. Results In EMBODY™ 1/EMBODY™ 2, 793/791 patients were randomized, 786 (99.1%)/788 (99.6%) received study medication, and 528 (66.6%)/533 (67.4%) completed the study. There was no statistically significant difference in the primary endpoint between groups: Week 48 BICLA response rates were similar in epratuzumab and placebo groups (range 33.5–39.8%). No new safety signals were identified. Conclusions Treatment with epratuzumab+ST did not result in improvements in response rates over placebo+ST. This article is protected by copyright. All rights reserved.