Assays Reveal Equivalence Between Adalimumab-aqvh and Humira

Researchers compiled countless assays on originator adalimumab (Humira), in comparison to the biosimilar, adalimumab-aqvh, showing comparable safety and efficacy between the products in their study, which was published in Drugs in R&D.

Adalimumab-aqvh was approved in July 2023 by the FDA under the brand name, Yusimry, to treat rheumatoid arthritis, hidradenitis suppurativa, Crohn disease, ulcerative colitis, juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis. Since the approval of the biosimilar, assessments on the physiochemical and functional attributes between the originator and adalimumab-aqvh have included quality factors based on mechanism of action.

Various materials and methods were applied for the comparative analytical assessment, based on risk ranking of the product quality attributes. The results were either similar criteria between the originator and adalimumab-aqvh or they were identical. Both adalimumab and adalimumab-aqvh had visible stability with functional activities.

Of the assorted methods, the majority of all principles were met to standard. The primary structure exhibited parallel peptides with the same masses, confirming 100% coverage. The higher order structure’s fluorescence profiles and emission maxima were also comparable between adalimumab and adalimumab-aqvh. Glycosylation in both medications were identical in most glycan categories, aside from terminal galactose and sialic acid. The high-molecular-weight species were proportionate outcomes among both drugs, meeting acceptance criteria yet again.

Slight differences were amid the originator adalimumab and the biosimilar. For starters, adalimumab-aqvh size variants were either similar or expressed a lower-molecular-weight species, resulting in greater monomer in relative areas. Charge variants, measured by cation-exchange chromatography, differed in acidity with only 1 adalimumab-aqvh lot above the range of the originator. The hydrophobic variables included oxidized fragment crystallizable (fc) variants within the average data, excluding one lot. Post-translational modifications had similar outcomes in all 5 levels monitored by adalimumab and adalimumab-aqvh. Free thiol and host-cell proteins had lower numbers in adalimumab-aqvh when compared to the originator drug but both categories achieved accepted criterion.

Overall, adalimumab-aqvh received identical numbers of or slightly fewer non-spherical particles than originator adalimumab. In areas surrounding fragment antigen-binding (fab) associated biological activity, the association constant and disassociation rate constant had similarities between both medications. The binding of membrane tumor necrosis factor-α with adalimumab and adalimumab-aqvh had similar results. An assay based on fab- and fc-associated biological activity had accepted variability, despite the biosimilar above the range of antibody dependent cell cytotoxicity. Partial disparities in biosimilars did not affect CDC activity in comparison to the originator lots. Binding affinity was similar in both medications with a fairly lower binding affinity outside of the 3 standard deviation range of the originator.

The stable data selected through assays encourages the biosimilarity support of similar functions between adalimumab and adalimumab-aqvh. Despite brief differences, similarity criteria were met for most of the glycan categories, amino acid sequences, and disulfide structures. There was no significant impact on the potency or efficacy in the minor physicochemical differences. The authors concluded, “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.”

Reference

Jiang Y, Arora T, Klakamp S, et al. Demonstration of physicochemical and functional similarity of biosimilar adalimumab-aqvh to adalimumab. Drugs R D. 2023;23(4):377-395. doi:10.1007/s40268-023-00437-3