Pharmacokinetics of a proposed tocilizumab biosimilar (MSB11456) versus US-licensed tocilizumab: results of a randomized, double-blind, single-intravenous dose study in healthy adults.

BACKGROUND

Tocilizumab, a recombinant monoclonal immunoglobulin G, targets the interleukin-6 receptor. MSB11456 is a proposed tocilizumab biosimilar.

OBJECTIVES

To assess pharmacokinetic equivalence of intravenous MSB11456 to US-licensed tocilizumab.

RESEARCH DESIGN AND METHODS

In this double-blind, parallel-group, single-dose study, 128 healthy adults were randomized to a single one-hour 8 mg/kg IV infusion of either MSB11456 or US-licensed tocilizumab. Blood samples were collected pre-dose and at regular intervals up to day 48 post-dose. The primary endpoint pharmacokinetic parameter was analyzed using analysis of variance (ANOVA) model on the natural logarithm of the endpoint (AUC), with treatment as a fixed effect. Immunogenicity and safety data were summarized descriptively.

RESULTS

Subjects received either MSB11456 (N = 62) or US-licensed tocilizumab (N = 66). Pharmacokinetic bioequivalence, defined as 90% confidence intervals for the geometric least squares mean ratio entirely contained within the 80.00% to 125.00% equivalence limits, was demonstrated between MSB11456 and US-licensed tocilizumab for the primary and secondary pharmacokinetic endpoints. Anti-drug antibody responses, frequency of neutralizing antibodies against tocilizumab, and safety profiles showed no notable between-treatment differences. Safety was comparable between treatments.

CONCLUSIONS

Pharmacokinetic similarity of MSB11456 and US-licensed tocilizumab was demonstrated, with comparable immunogenicity and safety profiles, supporting MSB11455 as a biosimilar to US-licensed tocilizumab. The trial is registered at EudraCT, number 2019-003484-22.