Clinical and Regulatory Considerations for the Use of Bevacizumab Biosimilars in Metastatic Colorectal Cancer

Abstract

Biosimilars e biological medicines highly similar to a licensed reference product (RP) e can mitigate the risk of drug shortages by providing treatment alternatives and, with their lower costs, increase patient access to medication and reduce health care expenditure. However, limited knowledge of biosimilar approval processes and lack of confidence in their quality and efficacy can limit their uptake. Importantly, biosimilars are approved based on tightly controlled regulatory pathways to demonstrate that the physical, chemical, and biological properties of the proposed biosimilar are highly similar to the RP, with no clinically meaningful differences. Initially, a battery of highly sensitive in vitro studies are performed, comparing critical quality attributes between the proposed biosimilar and RP. Subsequently, in vivo pharmacodynamic studies compare the activity and physiologic effects of the biosimilar and RP. Finally, clinical studies are conducted, including a pharmacokinetic equivalence study and a confirmatory comparative clinical trial. The latter is performed in the most sensitive patient population for which the RP is licensed, to provide the greatest possibility of identifying any clinically meaningful differences between the proposed biosimilar and RP. When equivalent safety and efficacy have been demonstrated in one setting, the totality of evidence, together with scientific justification that there are no anticipated differences between the RP and proposed biosimilar in mechanism of action, pharmacokinetics, immunogenicity or toxicity, allows extrapolation into indications where clinical studies were not performed with the proposed biosimilar. Here, we review the approval process for biosimilars, focusing on the licensing of bevacizumab biosimilars and their extrapolation to metastatic colorectal cancer.

Progress in oncology biosimilars till 2020: Scrutinizing comparative studies of biosimilar monoclonal antibodies

“…The potential difference among the proposed biosimilar of bevacizumab and reference product of bevacizumab were studied in non-small cell lung cancer which is considered a more sensitive population of patients than those suffering from metastatic colorectal cancer. 59 A biosimilar of bevacizumab PF-06439535 has shown no dissimilarity to bevacizumab reference of European Union as far as the efficacy is concerned. Safety parameters were identical too.…”

Application Progress of Bevacizumab in Neoadjuvant Therapy for Locally Advanced Rectal Cancer

“…Anti-tumor mechanism of bevacizumab, vascular endothelial growth factor (VEGF) plays a major part in the formation of tumor angiogenesis, and its high expression stimulates angiogenesis and cause the recurrence and metastasis tumor to be earlier. The drug belongs to recombinant humanized antivascular endothelial growth factor monoclonal antibody, which can selectively inhibit its biological activity in combination with VEGF [4,5]; bevacizumab includes framework segment containing human antibody and antigen-binding segment which can bind humanized mouse VEGF antibody; there are 214 kinds of amino acids in the drug, and the relative molecular mass is about 149×103. Bevacizumab can inhibit the binding of VEGF and the receptors Flt-1 and KDR on the surface of endothelial cells, thereby prompting the disappearance of the biological activity of VEGFR, reducing the formation probability of tumor blood vessel, and inhibiting tumor growth, as a result, the formed tumor blood vessels are normalized, reduces the permeability of tumor blood vessels, increases the concentration of chemotherapeutic drugs in tumor tissue, and can achieve the synergistic effect of chemotherapy.…”

Anlotinib: A Novel Targeted Drug for Bone and Soft Tissue Sarcoma

“…As a recombinant human monoclonal antibody, bevacizumab is the most-studied anti-angiogenic drug ( 84 , 85 ). The mechanism of action of bevacizumab is that by binding to VEGF, it prevents VEGF from binding to its natural receptor, VEGFR, and inhibits the proliferation and activation of vascular endothelial cells, so as to exert anti-angiogenesis and anti-tumor effects ( 86 , 87 ).…”