Adalimumab biosimilar(Mochida Pharmaceutical Co., Ltd.)

LBAL was developed as an adalimumab (Humira®) biosimilar using Chinese hamster ovary cell lines. Comparable quality, safety, and efficacy between a biosimilar and its reference product should be ensured for regulatory approval. Here, we present the results of a comprehensive physicochemical and biological characterization between LBAL and Humira®. As physicochemical attributes, primary and higher-order structure, N-glycan profile, and disulfide linkage were investigated. Biological attributes were evaluated by target/receptor binding analysis and in vitro/ex vivo cell-based assays, which are linked to mechanisms of action. As a result, LBAL had the identical amino acid sequence, similar post-translational modifications and N-/C-terminal variants, and comparable primary, secondary, and tertiary structures and disulfide linkage profile. However, some differences in N-glycan profiles were observed. Biological activities, including tumor necrosis factor (TNF) binding, TNF-neutralization, apoptosis, Fc receptor binding, and complement-dependent cytotoxicity, were largely consistent. Despite a slightly lower antibody-dependent cellular cytotoxicity activity in LBAL, this difference was not significant under physiological conditions. As indicated, this extensive analytical characterization and functional comparison assessment showed that LBAL was similar to Humira®, with minor differences of no clinical relevance. Taken together, our comparative assessment of physicochemical and biological attributes demonstrated that LBAL is structurally and functionally very similar to Humira®, supporting the biosimilarity of clinical efficacy and safety.

This study aimed to compare the pharmacokinetics (PK), immunogenicity, and tolerability of LBAL, a biosimilar of adalimumab, with the originator, Humira®, in healthy volunteers.

A randomized, double-blind, single-dose, two-arm, parallel-group study was conducted in 116 healthy subjects. They randomly received a single subcutaneous (SC) 40 mg injection of LBAL or Humira. Blood samples were collected for PK and immunogenicity assessment. PK parameters were determined using the noncompartmental method, and primary endpoint parameters were compared using the point estimates and 90% confidence intervals (CIs) of the geometric mean ratios (GMRs). Tolerability was also evaluated.

The PK characteristics of the test and reference drugs were comparable. The GMR (90% CIs) for C_max and AUC_inf of LBAL to Humira were 1.01 (0.92-1.11) and 0.96 (0.83-1.10), respectively, which were within the conventional bioequivalence criteria of 0.80-1.25. No significant differences occurred in the frequency of subjects with anti-adalimumab antibody-positive responses between both drugs. Tolerability profiles including adverse events were also comparable.

The PK characteristics of the biosimilar LBAL and the originator Humira were similar. LBAL and Humira did not show significant differences in immunogenicity and both were well tolerated after a single SC injection.