Rituximab biosimilar(Biocad Medical, Inc.)

BCD‐020 is a proposed rituximab biosimilar, which has shown high similarity to rituximab in quality and nonclinical studies in vitro and in vivo.International multicenter clinical trial was conducted to compare efficacy and safety of BCD‐020 and reference rituximab in adult (older than 18 years) patients with indolent lymphomas (follicular lymphoma grade 1‐2, splenic marginal zone lymphoma, and nodal marginal zone lymphoma). Pharmacokinetics, pharmacodynamics, and immunogenicity were also studied.Patients with no previous biologic treatment for lymphoma were randomly assigned 1:1 to receive BCD‐020 or comparator 375 mg/m2 for 4 weeks.Primary study outcome was day 50 overall response rate defined as complete or partial remission. Equivalence range was −20% to 20% for 95% CI for overall response rates difference. Secondary outcomes included adverse events, pharmacokinetics, pharmacodynamics, and immunogenicity.One hundred seventy‐four patients were enrolled, 89 in BCD‐020 arm and 85 in comparator arm. The overall response rate was 44.71% in BCD‐020 arm and 41.89% in comparator arm. Limits of 95% confidence interval (CI) for difference of overall response rates between arms were (−12.62%‐18.24%) showing equivalent efficacy. Sixty‐one (68.54%) and 59 (69.41%) patients had at least one adverse event in BCD‐020 arm or comparator arm, respectively. No unexpected adverse reactions were reported.Antidrug antibodies with no neutralizing activity were detected in two patients in comparator arm on day 14 further declining below detection threshold.Rituximab concentrations had equivalent pattern after intravenous administration of both drugs. Both drugs caused depletion of B‐cells without significant influence on other blood cell lineages.In this study, we showed equivalent efficacy of BCD‐020 and reference rituximab when used in patients with CD20‐positive indolent lymphomas. We also confirmed pharmacokinetic equivalence of BCD‐020 and reference rituximab. Safety profile, pharmacodynamics, and immunogenicity of BCD‐020 were also comparable with those of reference rituximab.

Biosimilars are poised to reduce prices and increase patient access to expensive, but highly effective biologic products. However, questions still remain about the degree of similarity and scarcity of information on biosimilar products from outside of the US/EU in the public domain. Thus, as an independent entity, we performed a comparative analysis between the innovator, Rituxan® (manufactured by Genentech/Roche), and a Russian rituximab biosimilar, Acellbia® (manufactured by Biocad). We evaluated biosimilarity of these two products by a variety of state-of-the-art analytical mass spectrometry techniques, including tandem MS mapping, HX-MS, IM-MS, and intact MS. Both were found to be generally similar regarding primary and higher order structure, though differences were identified in terms of glycoform distribution levels of C-terminal Lys, N-terminal pyroGlu, charge variants and soluble aggregates. Notably, we confirmed that the biosimilar had a higher level of afucosylated glycans, resulting in a stronger FcγIIIa binding affinity and increased ADCC activity. Taken together, our work provides a comprehensive comparison of Rituxan® and Acellbia®.