Bevacizumab Biosimilar MB02 Demonstrates Bioequivalence in Key Safety Parameters With Avastin

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A pooled analysis of 3 pharmacokinetic (PK) studies found comparable results in the bioequivalence margins, safety, and immunogenicity between MB02, a bevacizumab biosimilar, and the EU- and US-sourced reference product (Avastin).

Bevacizumab is a biologic medicinal product inhibiting angiogenesis by binding to vascular endothelial growth factor (VEGFs) and preventing its interaction with VEGF receptors on the surface of endothelial cells. The drug typically treats colorectal, nonsquamous non-small cell lung cancer, glioblastoma, kidney, cervical, and renal cell carcinoma.

The phase 1 studies were single-dose, double-blind, three-arm, parallel group designs. MB02-A-02-17 and MB02-A-05-18 analyzed the use of the EU-approved and US-approved reference product compared with the biosimilar in healthy Caucasian males. The third study (MB02-A-04-18) examined Japanese male participants treated with MB02 or the EU-sourced originator, where the duration covered more than 3.5 times the terminal half-life of bevacizumab.

MB02-A-02-17 collected data from 2 sites in the United Kingdom (UK) from November 2018 to May 2019, MB02-A-05-18 pooled data from a single center in Germany from September 2019 to March 2020, and MB02-A-04-18 contained data from a single Japanese center from August to December 2019.

All patients were randomized to receive a 3 mg/kg single 90-minute intravenous dose of either MB02, the reference EU-bevacizumab, or US-bevacizumab. The study population only included men, revealing few differences between demographics. The age range of the UK and German participants was 18 to 55 years, and the range for the Japanese participants was 20 to 55 years.

Study periods were 100 days for the UK and German studies, while the Japanese study lasted 70 days. Covance Laboratories performed the analyses with a validated enzyme-linked immunosorbent assay on their serum drug concentrations for MB02 and reference bevacizumab.

The PK parameters were measured by treatment group and as overall populations. The area under the serum concentration subtracted by the time curve measured from time zero and extrapolated to infinity did not express notable differences among MB02 or either of the EU- and US–reference bevacizumab groups (30258.8 vs 26091.65 vs 26436.53, respectively). The area under the serum concentration minus the time curve measured from time zero to the time of last quantifiable concentration did not include differences between the MB02 and EU- or US-bevacizumab groups (28811.74 vs 26091.65 vs 26436.53, respectively).

Maximum observed serum concentrations did not have any major differences among the 3 studies analyzed (MB02, 82.49; EU -bevacizumab, 77.57; US-bevacizumab, 71.92). The time of maximum observed serum concentration were almost identical between groups (MB02, 3; EU- and US-bevacizumab, 4). All pairwise comparisons within the studies had remained within the predefined bioequivalence margins, including the terminal half-life, total body clearance, and the volume of distribution during the terminal elimination phase.

Overall, 186 participants (67.4%) reported 483 treatment-emergent adverse events (TEAEs). Two reference bevacizumab groups had a higher report (166 TEAEs in EU-bevacizumab; 169 TEAEs in US-bevacizumab) of TEAEs compared with the MB02 group (148 TEAEs). The US-bevacizumab group had more TEAEs than the EU-bevacizumab and the MB02 group (80.3% vs 63% vs 62%, respectively). Most TEAEs were of mild severity and were similar between the studies (MB02, 52%; EU-bevacizumab, 43%; US-bevacizumab, 63.2%). The most frequent TEAEs were headaches and nasopharyngitis.

The MesoScale Discovery assay was utilized to determine the serum concentrations of antidrug antibodies. The studies had similar treatment induced antidrug antibodies developed in a total of 41 participants (MB02, 14%; EU-bevacizumab, 16%; US-bevacizumab; 14.47%). Five participants had neutralizing antibodies after treatment (MB02, .02%; EU-bevacizumab, .01%; US-bevacizumab, .03%).

The study populations limited the findings because the researchers did not correct the results from Asian participants to reflect the previous descriptions for bevacizumab PK characteristics. Additionally, the studies had short study periods and differing selected sampling schedules.

The authors noted that this is the largest known analysis in the field of biosimilar monoclonal antibodies, providing further evidence on PK similarities through larger populations.

Reference

Miguel-Lillo B, Sánchez-Vidaurre S, Pérez Díaz L, Paravisini A. Pooled analysis of three pharmacokinetic studies comparing biosimilar MB02 and reference bevacizumab. Pharmacol Res Perspect. 2023;11(6):e01139. doi:10.1002/prp2.1139