Data suggest that biosimilarity is demonstrated between reference and biosimilar adalimumab.
The structural, functional, and stability data give convincing evidence of biosimilarity between adalimumab-aqvh and the reference product, adalimumab, according to Drugs in R&D.
Adalimumab-aqvh/CHS-1420 (adalimumab-aqvh) was newly approved by the FDA as a biosimilar for adalimumab.
First, this study was conducted to evaluate the analytical similarity of adalimumab-aqvh and the reference product, adalimumab.
Even though adalimumab-aqvh and adalimumab have the same primary structure and sequence, some protein heterogeneity could be anticipated due to the inherent variation that can happen with biologic products are manufactured. Small differences as a result of post-translational modifications might happen during the production of biologics in living cells.
State-of-the-art assays were used to compare the structural, functional, and stability attributes of adalimumab-aqvh and adalimumab.
Then, the primary structure, disulfide structure, glycan profile, secondary and tertiary structures, molar mass, size variants, free thiol, charge variants, hydrophobic variants, post-translational modifications, subvisible particles, host cell proteins, and protein concentration were examined. The functional similarity between adalimumab-aqvh and adalimumab was shown by comparing fragment antigen-binding (Fab)- associated and fragment crystallizable (Fc)- associated biological activities. The stability of adalimumab-aqvh and of adalimumab was contrasted through forced degradation.
The structural qualities of adalimumab-aqvh were indistinguishable to those of adalimumab or met the similarity criteria, with some exceptions. Adalimumab-aqvh and adalimumab showed comparable stability profiles and functional activities. Any perceived differences in the physiochemical attributes did not influence the conclusion of similarity because they did not impact any functional activities related to the adalimumab mechanism of action.
Similarity criteria for adalimumab-aqvh was met for isoelectric point and molecular weight but was not met for protein concentration.
“However, after a process improvement, all subsequent lots were within the similarity range for protein concentration,” added the study authors.
Adalimumab-aqvh did not meet the criteria for percentage main peak by non-reduced capillary electrophoresis in sodium dodecyl sulfate, but the differences seen had no impact on potency or stability.
Still, there were differences in FcγRIIIa binding did not affect similarity in antibody-dependent cell-mediated cytotoxicity, activity.
“The differences in FcγRIIIa binding also did not affect the pharmacokinetics or safety of adalimumab-aqvh when evaluated in the clinical trial in which biosimilarity of adalimumab-aqvh to adalimumab was assessed,” said the study authors.
Furthermore, functional characterization using orthogonal assays for known, likely, and plausible mechanisms of action additionally supported similarity between adalimumab-aqvh and adalimumab. Adalimumab-aqvh and adalimumab showed comparable degradation profiles under stressed storage conditions.
“The similarities between adalimumab-aqvh and adalimumab predict similar efficacy and safety outcomes in clinical trials, which was confirmed by the pharmacokinetic, safety, immunogenicity, and efficacy clinical trials that have been conducted,” concluded the study authors.
Jiang Y, Arora T, Klakamp S, et al. Demonstration of physicochemical and functional similarity of biosimilar adalimumab-aqvh to adalimumab. Drugs R D. Published online August 26, 2023. Doi:10.1007/s40268-023-00437-3