BEVZ92 Highly Similar to Reference Bevacizumab in PK, Efficacy, Immunogenicity, and Safety

Notably, the study was conducted in patients with cancer, rather than in a healthy population, to generate evidence of pharmacokinetic (PK) equivalence in a scenario that reflects how the biosimilar would be used in clinical practice.

Bevacizumab, an anti—vascular endothelial growth factor (anti-VEGF) agent, is regularly used in combination with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) or fluorouracil, leucovorin, and irinotecan (FOLFIRI) regimens to treat metastatic colorectal cancer.

BEVZ92, a proposed bevacizumab biosimilar being developed by mAbxience, has been previously been demonstrated to be highly similar to the reference Avastin in term of primary structure, higher order structure, biological activity, and binding affinity to VEGF. In a newly published study, researchers have reported findings from a confirmatory trial in patients with metastatic colorectal cancer receiving first-line treatment with bevacizumab and FOLFOX or FOLFIRI.

Notably, the study was conducted in patients with cancer, rather than in a healthy population, to generate evidence of pharmacokinetic (PK) equivalence in a scenario that reflects how the biosimilar would be used in clinical practice.

Read more about biosimilar bevacizumab.

The open-label, randomized, controlled trial was conducted at 15 centers in South America, Asia, and Europe between 2014 and 2015. In total, 142 patients were randomly assigned 1:1 to receive either the biosimilar or the reference at a dose of 5 mg/kg on the first day of every cycle of chemotherapy. Patients were treated until disease progression, unacceptable toxicity, or withdrawal of consent.

The study’s primary outcomes were the truncated area under the concentration-versus-time curve calculated from start of the first infusion until start of the second infusion (AUC0—336h) and over a dosage interval at steady state (AUCss). The study’s prespecified bioequivalence margin was 80% to 125%.

The researchers report that the proposed biosimilar and its reference had similar median concentration—time PK profiles after 1 infusion and again at cycle 7, when a steady state was reached. The geometric mean ratio was 99.4% (90% CI, 90.5%-109.0%) for AUC0—336h and 100.0% (90.2%-112.0%) for AUCSS. As the 90% CIs for the ratio of geometric means for the primary endpoints were contained within the prespecified margin, bioequivalence for the products was demonstrated.

Efficacy was also similar between the 2 treatment arms; the objective response rate was 49% (95% CI, 37%-61%) in the biosimilar arm and 56% (95% CI, 44%-68%) in the reference arm. Clinical benefit was observed in 87% (95% CI, 77%-94%) of patients in the biosimilar arm and 92% (83%-97%) of patients in the reference arm. Median progression-free survival was 10.8 months (95% CI, 7.4-11.5) in the biosimilar arm and 11.1 months (95% CI, 8.6-12.8) in the reference arm.

The proportions of patients reporting treatment-emergent adverse events (TEAEs) during treatment were similar between groups; 69 patients receiving the biosimilar reported AEs versus 71 patients receiving the reference. The most frequently reported TEAEs were diarrhea and nausea. Among AEs of grades 3 or 4, neutropenia was the most commonly reported. Serious TEAEs were reported by 28% of patients in the biosimilar arm and 30% of patients in the reference arm. Death as a result of a TEAE occurred in 8 patients in the biosimilar arm and 5 patients in the reference arm. All patients were assessed for antidrug antibodies (ADAs); 2 patients receiving the biosimilar developed ADAs, as did 1 patient in the reference group.

The investigators concluded that BEVZ92 and its reference were highly similar in terms of PK, efficacy, immunogenicity, and safety, and when used in the same way as its reference, the proposed biosimilar can be expected to produce the same benefits as the innovator product at a lower cost.

Reference

Romera A, Peredpaya S, Shparyk Y, et al. Bevacizumab biosimilar BEVZ92 versus reference bevacizumab in combination with FOLFOX or FOLFIRI as first-line treatment for metastatic colorectal cancer: a multicentre, open-label, randomised controlled trial. [Published online September 24, 2018.] Lancet Gastroenterol Hepatol. doi: 10.1016/S2468-1253(18)30269-3.