Safety, pharmacokinetics, and pharmacodynamics of epratuzumab in Japanese patients with moderate-to-severe systemic lupus erythematosus: Results from a phase 1/2 randomized study

Abstract

Objectives: This 12-week, randomized, double-blind, placebo-controlled, multicenter phase 1/2 study (NCT01449071) assessed the safety, pharmacokinetics, and pharmacodynamics of epratuzumab in Japanese patients with moderate-to-severe systemic lupus erythematosus despite standard of care.

Methods: Twenty patients were randomized 1:1:1:1:1 to placebo or one of four epratuzumab dose regimens (100 mg every other week [Q2W], 400 mg Q2W, 600 mg every week [QW], or 1200 mg Q2W) administered during an initial 4-week dosing period. Adverse events (AEs), pharmacokinetics and pharmacodynamics were assessed.

Results: Nineteen of 20 patients completed the study. All placebo patients and 13 of 16 epratuzumab patients reported ≥1 AE, 2 of 16 epratuzumab patients reported a serious AE. C_max and AUC_τ increased proportionally with dose after first and last infusion, t_1/2 was similar across groups (∼13 days). Epratuzumab treatment was associated with decreased CD22 mean fluorescence intensity in total B cells (CD19⁺CD22⁺) and unswitched memory B cells (CD19⁺IgD⁺CD27⁺). Small-to-moderate decreases were observed in total B cell (CD20⁺) count.

Conclusions: Epratuzumab was well-tolerated, with no new safety signals identified. The pharmacokinetics appeared linear after first and last infusions. Treatment with epratuzumab was associated with CD22 downregulation and with small-to-moderate decreases in total B cell count.

Keywords:

• Epratuzumab
• Pharmacodynamics
• Pharmacokinetics
• Safety
• Systemic lupus erythematosus

Acknowledgements

We thank the patients, the investigators, and their teams who took part in this study. The authors acknowledge Jen Timoshanko, UCB Pharma, Slough, UK, for publication coordination, Sirisha Bulusu and Helen Chambers, Costello Medical Consulting, UK, for writing and editorial assistance, Tim Kopotsha for bioanalysis of plasma epratuzumab and ADA, and Tony Shock for bioanalysis of flow markers. Epratuzumab was licensed from Immunomedics Inc. (Morris Plains, NJ, USA) by UCB Pharma for clinical development and commercialization in all autoimmune disorders.

Conflict of interest

T. Tsuru has served as a consultant for UCB Pharma. Y. Tanaka has received consulting fees, speaking fees, and/or honoraria from Abbvie, Daiichi-Sankyo, Chugai, Takeda, Mitsubishi-Tanabe, BMS, Astellas, Eisai, Janssen, Pfizer, Asahi Kasei, Eli Lilly, GlaxoSmithKline, UCB Pharma, Teijin, MSD, and Santen and has received research grants from Mitsubishi-Tanabe, Takeda, Chugai, Astellas, Eisai, Taisho-Toyama, Kyowa-Kirin, Abbvie, and BMS. Y. Takasaki has acted as a consultant and/or served on speakers bureau for Santen, Daiichi-Sankyo, Mitsubishi Tanabe, BMS, AstraZeneca, Astellas, MSD, Chugai, Asahi Kasei, Eisai, and Janssen.

T. Koike has served as a consultant for BMS, Pfizer, and UCB Pharma and has served on speakers bureaus for Abbvie, Astellas, BMS, Chugai, Daiichi-Sankyo. Eisai, Mitsubishi-Tanabe, Pfizer, Santen, Takeda, Teijin, and UCB Pharma. J. Yamamoto, R. Lledo-Garcia, J. Shao, S. Tatematsu, and O. Togo are employees of UCB Pharma. All other authors have declared no conflicts of interest. This study was funded by UCB Pharma.

Supplementary material available online