A randomized, single-dose, pharmacokinetic equivalence study comparing MB02 (proposed biosimilar) and reference bevacizumab in healthy Japanese male volunteers

• Published in: Cancer chemotherapy and pharmacology Vol. 88; no. 4; pp. 713 - 722
• Main Authors: Eto, Takashi, Karasuyama, Yuji, González, Verónica, Del Campo García, Ana
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.10.2021; Springer Nature B.V
• Subjects: Adult; Adverse events; Angiogenesis Inhibitors - administration & dosage; Angiogenesis Inhibitors - adverse effects; Angiogenesis Inhibitors - pharmacokinetics; Area Under Curve; Asians; Bevacizumab; Bevacizumab - administration & dosage; Bevacizumab - adverse effects; Bevacizumab - pharmacokinetics; Biological products; Biosimilar Pharmaceuticals - administration & dosage; Biosimilar Pharmaceuticals - adverse effects; Biosimilar Pharmaceuticals - pharmacokinetics; Cancer Research; Double-Blind Method; Humans; Immunogenicity; Male; Medicine; Medicine & Public Health; Monoclonal antibodies; NCT; NCT04238650; Oncology; Original; Original Article; Pharmacokinetics; Pharmacology/Toxicology; Targeted cancer therapy; Young Adult; Biosimilars; Safety; MB02; Pharmacokinetics; Japanese; Bevacizumab
• ISSN: 0344-5704; 1432-0843; 1432-0843
• DOI: 10.1007/s00280-021-04324-z

Purpose MB02 is a biosimilar to bevacizumab that has demonstrated similar physicochemical and functional properties in in vitro studies to the reference bevacizumab (Avastin ® ). This study aims to assess the pharmacokinetic (PK) similarity of MB02 to the reference bevacizumab in Japanese population. Methods This double-blind, randomized, parallel-group, single-dose PK study, was performed in healthy Japanese male volunteers. Subjects were equally randomized (1:1) to receive a single (3 mg/kg) IV dose of MB02 or reference bevacizumab. PK assessments were done up to 70 days post-dose. Non-compartmental parameters were calculated. PK similarity was determined using predefined equivalence range (0.80–1.25) for the area under the serum concentration–time curve from time 0 extrapolated to infinity (AUC 0–∞ ). Immunogenicity samples were taken pre-dose and up to day 70. Safety was assessed throughout the study. Results In total, 48 subjects (24 in each treatment group) were dosed. Consequently to the observed similar PK profile, the 90% confidence interval for the geometric means ratio for the primary PK endpoint, AUC 0–∞ , was within the predefined equivalence range (0.981–1.11). Forty-seven treatment-emergent adverse events (TEAEs) were reported in 20 subjects (41.7%) with comparable incidence among MB02 and reference bevacizumab groups (22 and 25, respectively), none of them was severe or serious. Anti-drug antibodies incidence was low and similar between treatment groups. Conclusions Pharmacokinetic similarity of MB02 to reference bevacizumab was evidenced in Japanese healthy subjects, with comparable safety and immunogenicity profile between treatments. This study supports the biosimilarity of MB02 to reference bevacizumab in Japanese population. ClinicalTrials.gov identifier: NCT04238650.