The impending “patent cliff” for billon dollar monoclonal antibody drugs (mAbs), the enactment of the Biologics Price Competition and Innovation Act, and the newly issued US FDA guidance on biosimilar products has opened the door for numerous biosimilar applications. Remsima™ is a mimic of a nine billion dollar product Remicade® is in line to become the first approved biosimilar mAb in the US and was the first mAb biosimilar approved in Europe, and is also approved in South Korea and Canada. Questions regarding the uses of analytical comparison to show similarity and extrapolation of indications are still unresolved, as differences in glycosylation profiles and in vitro receptor binding were observed for the two products and led to limited indication for Remsima in Canada. Regulators, however, agree that bisomiliar applications must start with a thorough analytical comparison of the products, but analytical characterization of mAbs is challenging due to their large size (~150 kDa) and complex nature owing to intrinsic and process driven heterogeneities. We compared multiple lots of Remsima™ and Remicade® for critical quality attribute differences using an optimized LC-MS workflow coupled with powerful statistical software. Samples were quantitatively compared according to levels of oxidation, deamidation, terminal lysine truncation, glycation, glycosylation, disulfide bond formation and sequence variance; the products were highly similar for these parameters. Noticeable differences were observed in the levels of glycation and N-glycan forms (figure A), with Remicade having 20% and Remsima having 13% a-fucosylated forms. Follow on binding studies suggest that Remicade binds to FcγIIIa receptors tighter than Remsima, KD 162 ± 18 vs. 351 ± 48 nM (figure B). Increased fucsoylation, and glycation, coupled with weaker receptor binding could translate to reduced efficacy in treatment of inflammatory bowel disease and warrants further investigation.

Characterization and quantitative comparison of remicade and its biosimilar remsima

251st National Meeting (2016)

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