Get the knowledge about biosimilars with our course director Dr. Alex Kudrin, MD, MBA, Ph.D.
Dr Alex Kudrin, MD, MBA, PhD
Biosimilars are biological recombinantly derived products with similar analytical, functional, efficacy, and safety features to a licensed originator/reference medicinal product (RMP). Biosimilars include monoclonal antibodies, soluble receptors, growth factors, and hormones. The recent and upcoming generation biosimilars includes copies of anti-TNF (adalimumabs, infliximabs, etanercepts, golimumabs), anti-CD20 (rituximabs, ocrelizumabs, obinutuzumabs), ant-IL12/IL23 (ustekinumabs), anti-IL6 (tocilizumabs), anti-HER2 (trastuzumabs and pertuzumabs), anti-VEGF (bevacizumabs), anti-EGFR (cetuximabs), anti-PD1 (pembrolizumabs and nivolumabs), and many other monoclonal antibodies against chronic inflammatory, degenerative and oncologic diseases.
The main objective for biosimilars is to reduce healthcare costs and it is anticipated that emergence of several biosimilars of the same class can drive prices down by 30-80%. Overall the biosimilar field is extremely competitive now with multiple companies and products placed into the market space at the same time. Lean and low cost strategy in development and commercialization of biosimilars is pivotal in ensuring the survival of biosimilar sponsors and business as a whole.
An inherent micro-heterogeneity of biological products is driven by presence of multiple species with distinct or slightly different glycosylation profiles in the same vial of the product. These species can generate different structural, functional, PK and efficacy attributes, as well as can confer different stability profile.
The manufacturing of biosimilars is a complex multistep process; factors at each stage, such as production cell line, culture conditions, and formulation, may each alter the final product through post-translational modifications and other structural features, e.g. aggregation or truncation. Whereas the focus for the manufacturer of the RMP is to demonstrate a favorable benefit-risk balance in clinical trials, biosimilar development focuses on confirmation that the biosimilar is highly similar to RMP in terms of structure, composition, purity potency and in vitro activities. Therefore, the critical quality attributes of a biological drug that can impact pharmacology, clinical safety and efficacy should be carefully assessed. At least one clinical study is required to compare pharmacokinetics of RMP and a biosimilar, and at least one sufficiently powered randomised controlled trial to demonstrate clinical non-inferiority or equivalence in the most homogenous and sensitive therapeutic setting. Any residual uncertainties from the analytical similarity, manufacturing development and non-clinical studies should be adequately addressed and resolved in these clinical studies.
Once biosimilarity is confirmed, there could be scientific grounds for extrapolation of non-studied indications licensed for RMP, provided there is a shared or similar mechanism of action and toxicities profile in each condition. Consequently, a biosimilar can be approved in all indications for which the RMP has been approved, without multiple clinical trials.