AUTHOR=Cao Guoying , Wang Jingjing , He Jinjie , Hu Yingying , Yang Haijing , Que Linling , Gu Xianghong , Yu Jicheng , Wu Xiaojie , Wu Jufang , Fang Wei , He Qing , Zhang Jing 

TITLE=LZM008, a proposed tocilizumab biosimilar: Pharmacokinetics, safety, and immunogenicity profiles compared with ACTEMRA® in Chinese healthy male subjects

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1111893

DOI=10.3389/fphar.2023.1111893

ISSN=1663-9812

ABSTRACT=Background: 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 tocilizumab (Actemra®) 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 1:1 ratio to receive 4 mg/kg intravenous dose of 
LZM008 or (Actemra®), and evaluated for 28 days. The pharmacokinetic bioequivalence was assessed by the maximum serum concentration (Cmax), the area under the serum concentration-time curve (AUC) from time 0 to the last detectable drug concentration (AUC0-t) , and AUC0-∞.The statistical analysis was conducted by SAS enterprise guide statistical software. Safety was assessed by physical examinations, vital signs, laboratory tests, and electrocardiograms. Anti-drug antibodies (ADAs) were measured by bridged electrochemiluminescence immunoassay. 
Results: LZM008 (N=49) and Actemra® (N=47) groups showed similar PK properties. After single intravenous infusion of 4 mg/kg LZM008, the Cmax and AUC0-∞ of LZM008 reached at 87.99 μg/mL and 11526.70 h*μg/mL with Tmax 1.98 h, and the half-life (t1/2) was 83.45 h. The 90% confidence intervals of ratios for Cmax, AUC0-t and AUC0-∞ were within the range of 80.00%-125.00%. After infusion, One (2.0%) subject in LZM008 group and three (6.4%) subjects in Actemra@ group showed positive ADA test results. The incidence of treatment emergent adverse events (TEAEs) was comparable in the LZM008 and Actemra@ groups (98.0% versus 100%), with blood fibrinogen decreased and neutrophil counts decreased being the most common TEAEs. 
Conclusions: The pharmacokinetic characteristics and immunogenicity exhibited by LZM008 were similar to that of the reference product, Actemra®. The safety profiles of LZM008 was similar in the two group with mild-moderate adverse effects.