FRI0383 Safety, Pharmacokinetics, and Pharmacodynamics of Epratuzumab in Japanese Patients with Moderate-To-Severe Systemic Lupus Erythematosus: Results from A Phase 1/2 Study

Background Treatment with epratuzumab, a humanized monoclonal antibody targeting CD22 on B cells, has been associated with improvements in disease activity in patients (pts) with moderate-to-severe systemic lupus erythematosus (SLE) with an acceptable safety/tolerability profile and moderate reductions in B cell levels. Objectives To assess safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of epratuzumab in Japanese pts with moderate-to-severe SLE in addition to standard of care treatments. Methods Japanese pts were randomized 1:1:1:1:1 to placebo (PBO) or epratuzumab (100mg/400mg/1200mg every other week [wk] [Q2W] or 600mg every wk [QW]) for a 4-wk dosing period at the beginning of the 12-wk study. Pts had moderate-to-severe SLE (BILAG A disease activity in ≥1 or BILAG B disease activity in ≥2 body systems). Levels of plasma epratuzumab, human anti-human antibodies (HAHA) to epratuzumab, B cells, T cells and mean fluorescence intensity (MFI) of B cell CD22 were measured and results summarized using descriptive statistics. PK parameters were computed by non-compartmental methods. Adverse events (AEs) and laboratory parameters were assessed. Results 19 of 20 randomized pts (95.0%) completed the study; 1 pt (1200mg Q2W group) discontinued due to an AE. PK appeared to be linear: after first and last epratuzumab infusion Cmax and AUCτ increased proportionally to dose (Table). t1/2 was approximately 13 days and similar across groups. No pts were HAHA positive during the study (antibody concentration >2-fold the limit of quantitation; 62ng/mL). There were small-to-moderate decreases in total B cell (CD20+) counts in all epratuzumab groups (median change from baseline: -43.2% to 10.0%), no trend was seen with dose or regimen. Total T cell (CD3+) counts showed no consistent trends in any treatment group. A pharmacological effect on median CD22 MFI was observed in all epratuzumab groups: Wk1 median change from baseline was -3360 to -4092 on total B cells (CD19+CD22+) and -2147 to -2805 on memory B cells (CD19+IgD+CD27+). Decreases were maintained in 400mg Q2W/1200mg Q2W/600mg QW groups whilst increasing towards baseline in the 100mg Q2W group after Wk4 (median change on memory B cells: -954 and -674 at Wks 8 and 12, respectively). All PBO pts and 13/16 epratuzumab pts reported ≥1 AE, all mild-moderate in intensity. Most commonly reported AEs were in the system organ class of infections and infestation (7/16 pts; 43.8%). Serious AEs were reported