AI Article Synopsis
- ABP 959 is a proposed biosimilar to eculizumab, a monoclonal antibody used to treat various serious conditions by inhibiting the C5 complement protein.
- This study aimed to compare the structural and functional similarities between ABP 959 and the reference product using advanced analytical methods.
- Results indicated that ABP 959 has the same amino acid sequence, similar structures, and biological activity as eculizumab, supporting its classification as analytically similar to the original product.
Article Abstract
Background: ABP 959 is one of the first proposed biosimilars to eculizumab reference product (RP), a recombinant IgG2/4 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8502742 | PMC |
| http://dx.doi.org/10.1007/s40259-021-00492-9 | DOI Listing |
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