Abevmy Mechanism of Action

Pharmacotherapeutic Class: Antineoplastic and immunomodulating agents/antineoplastic agents/other antineoplastic agents/monoclonal antibodies. ATC Code: L01X C07.
Pharmacology: Pharmacodynamics: Mechanism of Action: Bevacizumab is a recombinant humanised monoclonal antibody that selectively binds to human vascular endothelial growth factor (VEGF) and neutralises its biologic activity. ABEVMY is produced by recombinant DNA technology in a Chinese Hamster ovary mammalian cell expression system in a nutrient medium containing the antibiotic gentamicin, and is purified by a process that includes specific viral inactivation and removal steps. By binding to VEGF, bevacizumab blocks the interaction of VEGF and its receptors (Flt-1 and KDR), present on the surface of endothelial cells. Bevacizumab inhibits the formation of tumour vasculature, thereby inhibiting tumour growth. In xenograft cancer models in nude (athymic) mice, bevacizumab or the parent murine antibody had notable anti-tumour activity, and inhibited metastatic disease progression as well as reduced microvascular permeability.
Pharmacokinetics: A double-blind, randomized, active-controlled, parallel-arm, comparative PK, efficacy, safety and immunogenicity study of ABEVMY and bevacizumab (Reference Product), both in combination with capecitabine and oxaliplatin in patients with metastatic colorectal cancer (mCRC) showed that the pharmacokinetic profile of ABEVMY was similar to that of bevacizumab.
Clinical Efficacy: The clinical efficacy of ABEVMY was assessed in a double-blind, randomized, active-controlled, parallel-arm, comparative PK, efficacy, safety and immunogenicity study of ABEVMY and bevacizumab (Reference Product), both in combination with capecitabine and oxaliplatin in patients with first-line mCRC. There were no significant differences between ABEVMY and bevacizumab with regard to efficacy in terms of progression-free survival (PFS) rate, clinical benefit (disease control rate [DCR]), or overall response rate (ORR).
Toxicology: Preclinical Safety Data: During conventional single- and repeat-dose toxicity studies of ABEVMY in mice, rabbits, and cynomolgus monkeys, no clinically relevant adverse events were observed at the highest dose levels tested. Local tolerance was also evaluated in these toxicity studies, and no clinically relevant effects were observed. No meaningful differences were observed between the toxicity profiles of ABEVMY and bevacizumab (Reference Product). The inhibition of angiogenesis following administration of bevacizumab may result in an adverse effect on female fertility.