LZM008, a proposed tocilizumab biosimilar: Pharmacokinetics, safety, and immunogenicity profiles compared with ACTEMRA((R)) in Chinese healthy male subjects

Background: This study aimed to investigate the pharmacokinetics, safety, and immunogenicity of recombinant humanized anti-human IL-6R monoclonal antibody injection, LZM008, and evaluate the pharmacokinetic similarity between LZM008 and wtocilizumab (ACTEMRA (R)) in Chinese healthy male subjects. Research design and methods: In this randomized, double-blinded, paralleled, two-center Phase I clinical trial, 96 subjects were randomized with a 1:1 ratio to receive 4 mg/kg intravenous dose of LZM008 or ACTEMRA (R) and evaluated for 28 days. The pharmacokinetic bioequivalence was assessed by the maximum serum concentration (C-max), the area under the serum concentration-time curve (AUC) from time 0 to the last detectable drug concentration (AUC(0-t)), and AUC(0-infinity). The statistical analysis was conducted using SAS Enterprise Guide statistical software. Safety was assessed by physical examinations, vital signs, laboratory tests, and electrocardiograms. Anti-drug antibodies (ADAs) were measured by a bridged electrochemiluminescence immunoassay. Results: LZM008 (N = 49) and ACTEMRA (R) (N = 47) groups showed similar pharmacokinetic properties. After a single intravenous infusion of 4 mg/kg LZM008, the C-max and AUC(0-infinity) values of LZM008 reached 87.99 mu g/mL and 11,526.70 h*mu g/mL, respectively, with T-max 1.98 h, and the half-life (t(1/2)) was 83.45 h. The 90% confidence intervals of ratios for C-max, AUC(0-t), and AUC(0-infinity) were within the range of 80.00%-125.00%. After infusion, one (2.0%) subject in the LZM008 group and three (6.4%) subjects in the ACTEMRA (R) group showed positive ADA test results. The incidence of treatment emergent adverse events (TEAEs) was comparable in LZM008 and ACTEMRA (R) groups (98.0% versus 100%), with the decrease in blood fibrinogen and neutrophil counts being the most common TEAEs. Conclusion: The pharmacokinetic characteristics and immunogenicity exhibited by LZM008 were similar to those of the reference product, ACTEMRA (R). The safety profiles of LZM008 were similar in the two groups with mild-moderate adverse effects.