Demonstration of physicochemical and functional similarity between the proposed biosimilar adalimumab MSB11022 and Humira®

Abstract

Biosimilars are biological products that are highly similar to existing products approved by health authorities. Demonstration of similarity starts with the comprehensive analysis of the reference product and its proposed biosimilar at the physicochemical and functional levels. Here, we report the results of a comparative analysis of a proposed biosimilar adalimumab MSB11022 and its reference product, Humira®. Three batches of MSB11022 and up to 23 batches of Humira® were analyzed by a set of state-of-the-art orthogonal methods. Primary and higher order structure analysis included N/C-terminal modifications, molecular weight of heavy and light chains, C-terminal lysine truncation, disulfide bridges, secondary and tertiary structures, and thermal stability. Purity ranged from 98.4%–98.8% for MSB11022 batches (N = 3) and from 98.4%–99.6% for Humira® batches (N = 19). Isoform analysis showed 5 isoform clusters within the pI range of 7.94–9.14 and 100% glycan site occupancy for both MSB11022 and Humira®. Functional analysis included Fab-dependent inhibition of tumor necrosis factor (TNF)-induced cytotoxicity in L929-A9 cell line and affinity to soluble and transmembrane forms of TNF, as well as Fc-dependent binding to Fcγ and neonatal Fc receptors and C1q complement proteins. All tested physicochemical and functional parameters demonstrated high similarity of MSB11022 and Humira®, with lower variability between MSB11022 and Humira® batches compared with variability within individual batches of Humira®. Based on these results, MSB11022 is anticipated to have safety and efficacy comparable to those of Humira®.

Comparison of the pharmacokinetics, safety, and immunogenicity of MSB11022, a biosimilar of adalimumab, with Humira® in healthy subjects

“…MSB11022 showed comparable physicochemical and in vitro primary pharmacodynamic properties to US-RP/EU-RMP. By testing several commercial scale drug product lots of MSB11022 and US-RP/EU-RMP, the Fab activities for binding to human soluble and membrane bound forms of TNF and for the inhibition of TNF-induced cytotoxicity, as well as the Fc binding to neonatal Fc receptor, Fc-γ receptors and C1q complement protein, were shown to result in affinities and potencies for MSB11022 that fall within the range established by the US-RP/EU-RMP [9]. In addition to the physicochemical and in vitro functional testing, a comparative, repeat-dose, toxicity study in Cynomolgus monkeys was conducted.…”

AURIEL ‐PsO: a randomized, double‐blind phase III equivalence trial to demonstrate the clinical similarity of the proposed biosimilar MSB 11022 to reference adalimumab in patients with moderate‐to‐severe chronic plaque‐type psoriasis

“…Regulatory approval of biosimilars requires evidence that the molecule is similar to the reference product in terms of structure, function, clinical efficacy and safety . MSB11022 (Idacio ® ) is a proposed adalimumab biosimilar that has been shown to be structurally and functionally similar to reference adalimumab based on extensive analytical characterization . The pharmacokinetic bioequivalence of MSB11022 and reference adalimumab (both European Union and U.S.A. approved versions) has been shown in a phase I study .…”

Novel chemical degradation pathways of proteins mediated by tryptophan oxidation: tryptophan side chain fragmentation

“…Trp side chain cleavage), which was subsequently confirmed to proceed under exposure to ambient light . Forced degradation (including thermal forced degradation) has also become an important tool for biosimilar analysis . However, certain limitations of forced degradation studies of proteins must also be acknowledged.…”