A phase 1 clinical trial in China comparing the tocilizumab biosimilar candidate LZM008 (Livzon Mabpharm) to the reference product (Actemra) found pharmacokinetic (PK) parameters within the bioequivalence margins and similar immunogenicity and safety in healthy participants.

Tocilizumab is a recombinant humanized monoclonal antibody to the interleukin-6 receptor. The originator is approved to treat rheumatoid arthritis (RA) in China, the United States, and Europe. Preclinical studies demonstrated “high similarities” between LZM008 and the originator, the authors said, adding that, at the time of writing, there was no biosimilar tocilizumab product available in China. China’s National Medical Products Administration approved Bio-Thera Solutions’ tocilizumab biosimilar BAT1806 for RA in January 2023.

The randomized, double-blind study evaluated PK, safety, and immunogenicity parameters for 28 days following a single intravenous dose of the biosimilar (n = 49) or reference product (n = 47). The investigators said the 2 groups were “well balanced and comparable” regarding demographics and baseline characteristics.

PK Parameters Met Equivalence Criteria

Similar PK properties were observed, with 90% CI of ratios for all pharmacokinetic parameters measured within the equivalence range of 80% and 125%. CIs for the primary endpoints maximum serum concentration (Cmax) and area under the concentration-time curve (AUC) from time 0 to the last detectable drug concentration (AUC0-t) were 105% to 119% and 103% to 115%, and 105% to 119% for the secondary endpoint AUC from time 0 to infinity (AUC0-∞). “Overall, PK profiles were similar in the two groups and can meet the bioequivalence criterion.”the authors concluded.

Safety and Immunogenicity

The incidence of treatment emergent adverse events (TEAEs) was similar in the LZM008 and reference tocilizumab groups, with 98% and 100% of patients experiencing TEAEs, respectively. The most common were decreases in blood fibrinogen and neutrophil counts. In the biosimilar group 8% of subjects had TEAEs of grade 3 or worse compared to 13% in the reference product group. No serious adverse events or TEAEs leading to discontinuation of treatment or death were observed. All grade 4 TEAEs resolved after day 36.

At day 28, 1 (2%) participant in the LZM008 group and 3 (6%) in the reference product group had positive anti-drug antibody (ADA) results. Also, 1 subject in the reference product group was positive for neutralizing antibodies. However, the authors noted there were no AEs attributable to these ADA findings, and the PK profiles of patients with ADAs were similar to those of ADA-negative subjects.

Reference

Cao G, Wang J, He J, et al. LZM008, a proposed tocilizumab biosimilar: Pharmacokinetics, safety, and immunogenicity profiles compared with ACTEMRA® in Chinese healthy male subjects. Front Pharmacol. 2023;14:1111893. doi:10.3389/fphar.2023.1111893

Source:- Center For Biosimilars