Physicochemical and biological characterization of the Rituximab biosimilar RTXM83

BES, C; PESCE, A; CERUTTI, M.L; SEIGELCHIFER, M

Ciudad Autónoma de Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Biosimilars are biologic drugs designed to be similar to existing biopharmaceutical products for which patents have expired. Even though there are already approved Biosimilars in Europe and USA, the biosimilar manufacturing industry is also flourishing in emerging markets such as LatAm, Russia and Asia, where biosimilar adoption represents a strategic avenue to provide high quality and clinically effective medications at reduced cost. Rituximab is a chimeric monoclonal antibody approved for Non-Hodgkins lymphoma, chronic lymphocytic leukemia, and some autoimmune conditions. It is targeted against the pan-B-cell marker CD20 and exerts its therapeutic action through three different mechanisms of cell destruction: direct signaling of apoptosis, complement activation and cell-mediated cytotoxicity. We herein present the development and physicochemical and functional characterization of the Rituximab biosimilar RTXM83. In accordance with the guidelines established by International Regulatory Agencies such as the EMA and the FDA, the critical quality attributes of RTXM83 were evaluated in a comparability exercise to its reference product (RP) using an orthogonal approach. Some of the methodologies employed in this study are: peptide mapping and MS analysis, CD spectroscopy, SDS-PAGE, SE HPLC and glycan and charge variants analysis by chromatography, SPR binding assays and cell-based potency bioassays. The results indicate that the primary and higher order protein structures as well the post-translational modifications and impurity profiles of RTXM83 are similar to the RP. RTXM83 also showed similarity to the RP in terms of ADCC, CDC and apoptosis potency and binding affinities to CD20, C1q and a complete panel of Fc Receptors. Overall, these data reveal that RTXM83 can mimic the described mechanisms of action of Rituximab and provide confidence that it will match the potency and safety of the reference product in ongoing clinical trials.