Pharmacokinetics, Pharmacodynamics and Safety of Belimumab in Chinese Patients with Systemic Lupus Erythematosus: A Phase I, Open-Label Study

Introduction The B cell survival factor B lymphocyte stimulator (BLyS) is elevated in patients with systemic lupus erythematosus (SLE) and associated with disease activity. Belimumab, a monoclonal antibody specific for soluble BLyS, is approved for the treatment of adults with active, autoantibody-positive SLE receiving standard therapy. Ethnicity is one of the factors that can potentially affect the pharmacokinetics (PK) of therapeutic monoclonal antibodies, and therefore their efficacy and safety. Methods This phase 1, open-label study (200909) evaluated the pharmacokinetics (PK, primary objective), pharmacodynamics (PD), and safety (secondary objectives) of belimumab in Chinese patients with SLE (N = 20). Blood samples were taken up to 84 days after a single intravenous (IV) dose of belimumab 10 mg/kg. Results Peak serum concentrations of belimumab (C-max) were obtained within the 1-h infusion. Geometric mean C-max, area under the concentration-time curve (time 0 to last quantifiable concentration), terminal half-life, systemic clearance, and volume of distribution were 221 mu g/mL, 2395 day center dot mu g/mL, 14.6 days, 4.06 mL/day/kg, and 85.7 mL/kg, respectively. Decreases in CD20(+), CD20(+)/CD27(-) naive, CD20(+)/CD69(+) active, CD20(+)/CD138(+) plasmacytoid, CD19(+)/CD27(BRIGHT)/CD38(BRIGHT) SLE subset, and CD20(-)/CD138(+) plasma B Cells post-dose were accompanied by an increase in CD20(+)/CD27(+) memory B cells. Four cases of upper respiratory tract infection (three mild, one moderate) and one case of mild pharyngitis were possibly drug-related; all resolved during the study. Conclusion PK of a single belimumab 10 mg/kg IV dose in Chinese patients with SLE were similar to those observed previously in Japanese and American (white and African-American) patients with SLE. PD results were consistent with belimumab inhibiting BLyS, and belimumab was well tolerated. These data support the use of belimumab in Chinese patients with SLE.