[pubmed] Analytical Similarity Assessment of ABP 959 in Comparison with Eculizumab Reference Product
Posté : 23 juil. 2021 12:00
BioDrugs. 2021 Jul 22. doi: 10.1007/s40259-021-00492-9. Online ahead of print.
ABSTRACT
BACKGROUND: ABP 959 is one of the first proposed biosimilars to eculizumab reference product (RP), a recombinant IgG2/4Ƙ monoclonal antibody (mAb) that binds human C5 complement protein and inhibits C5 cleavage to C5a and C5b, preventing the generation of the terminal complement complex C5b-9. Eculizumab RP is approved for the treatment of paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, myasthenia gravis in patients who are anti-acetylcholine receptor antibody positive, and neuromyelitis optica spectrum disorder in patients who are anti-aquaporin-4 antibody positive.
OBJECTIVES: The objective of this work was to comparatively assess analytical (structural and functional) similarity between ABP 959 and eculizumab RP using sensitive, state-of-the art analytical methods capable of detecting minor differences in product quality attributes.
METHODS: Comprehensive analytical (structural and functional) characterization utilizing orthogonal techniques was performed using multiple lots of ABP 959 and eculizumab RP over several years applying > 40 state-of-the-art assays. Comparisons were performed to investigate the primary structure and post-translational modifications including glycans, higher-order structure, particles and aggregates, product-related structures and impurities, thermal stability and forced degradation, general properties, and biological properties mediated by target binding.
RESULTS: Results confirmed that ABP 959 had the same amino acid sequence, similar primary structure, higher-order structure, post-translational profiles, and the same protein content and concentration (e.g., ABP 959: 9.4-10.0; eculizumab EU: 9.4-10.0; eculizumab US: 9.3-10.3 mg/mL) as well as biological activity as eculizumab RP.
CONCLUSIONS: Based on these results, it can be concluded that ABP 959 is analytically similar to eculizumab RP.
PMID:34296421 | DOI:10.1007/s40259-021-00492-9
Source: https://pubmed.ncbi.nlm.nih.gov/3429642 ... 3&v=2.14.5