Rituximab and biosimilars – equivalence and reciprocity

Abstract

Cancer is a debilitating disease affecting millions of people daily. Over the years, cancer treatment has advanced in leaps and bounds. Antibodies are important breakthrough therapeutic agents for cancer. These agents, proteins produced by B lymphocytes of the immune system in response to antigens, bind to receptors on cell surfaces so that the antigen–antibody complexes can be recognized and destroyed by phagocytes. While each B cell synthesizes only one kind of antibody, an entire population of different types of B cells and their respective antibodies are produced in response to various antigens to which the organism had been exposed. However, to be useful clinically, substantial amounts of a single antibody must be generated from a single ancestral B cell. These antibodies produced by a specific population of B cells are the monoclonal antibodies that have become the cornerstone of treatment for cancer and many immunologic illnesses. The purpose of this report is to provide an overview of the clinical development of biosimilars in clinical oncology, focusing on rituximab and like biosimilars.

Population pharmacokinetics of Reditux™, a biosimilar Rituximab, in diffuse large B-cell lymphoma

“…However, DRL demonstrated comparability of structures using circular dichroism studies, which is not accepted by US FDA as adequate proof of comparability. Furthermore, instead of conducting a head-to-head comparative trial, DRL demonstrated comparable objective response rates to historically reported outcomes with MabThera™ through a single-arm trial involving 67 patients [7].…”

“…From a regulatory perspective, the manufacturing processes of Reditux™ and MabThera™ are different [7]. However, DRL demonstrated comparability of structures using circular dichroism studies, which is not accepted by US FDA as adequate proof of comparability.…”

“…The variety of clinical uses of Rituximab coupled with lack of penetration of health insurance schemes in countries such as India means that MabThera™ is not affordable to majority of patients. In such a scenario, introduction of Reditux™ improved access to Rituximab which is evident from the fact that within 3 years of its introduction a sixfold increase in patients receiving Rituximab was observed [7].…”

“…Unlike small-molecule generics, the development and production of biosimilars is relatively complex [7]. In case of generics, proof of identical chemical composition with respect to the innovator followed by demonstration of bioequivalence is sufficient to get license for marketing [8].…”

Regulatory and clinical considerations for biosimilar oncology drugs

“…33 In India, before biosimilar rituximab approval, fewer than 1000 people received originator rituximab because of its high cost. 42 Since then, several thousand people have received biosimilar rituximab. In Russia, biosimilar rituximab approval and price discounts are expected, and therefore, presumably, overall use will increase.…”