Bioequivalence of MYL-1402O to EU- and US-reference bevacizumab

Biosimilares/Investigación | Posted 30/07/2021 post-comment0 Post your comment

The proposed bevacizumab biosimilar MYL-1402O demonstrated bioequivalence to European Union (EU)- and United States (US)-reference bevacizumab in a pharmacokinetic (PK) study of healthy adult male volunteers.

Bevacizumab 2 V14f01

Vascular endothelial growth factor (VEGF) is involved in angiogenesis in many cancers, and VEGF inhibition can help control cancer progression. The originator biological, Genentech’s Avastin (bevacizumab) is a recombinant humanized monoclonal antibody that binds to VEGF to inhibit its activity. Bevacizumab has demonstrated significant benefits in several cancer types, and it is approved in combination for multiple metastatic cancers in the US and the EU and as single-agent therapy for glioblastoma in the US.

Currently, at least 16 bevacizumab biosimilars are in development [1] and two have been approved by the US Food and Drug Administration (FDA) [2]. The proposed bevacizumab biosimilar MYL-1402O has the same amino acid sequence as reference bevacizumab. Hummel and colleagues recently reported results comparing pharmacokinetic (PK) parameters, safety, and tolerability of MYL-1402O with reference bevacizumab sourced from the US and the EU (ClinicalTrials.gov, NCT02469987; EudraCT, 2014-005621-12) [3].

A total of 111 healthy adult male volunteers aged 18 to 55 years (mean [SD] age, 31 [12] years) with no prior bevacizumab exposure were enrolled in this single-centre, randomized, double-blind, 3-arm, parallel-group, phase I clinical study. Participants were randomized 1:1:1 on day 1 and received a single 1 mg/kg dose of either MYL 1402O, EU-reference bevacizumab, or US-reference bevacizumab via intravenous infusion over 90 minutes. Use of healthy volunteers eliminated confounding health and treatment variables that may be associated with administration in patients with cancer, and subtherapeutic dosing was chosen to minimize drug exposure. Volunteers remained in the clinic on days 1 to 9, where serial blood sampling was performed within the first 12 hours after drug infusion and every day until clinic release, followed by a series of ambulatory visits up to day 99.

In keeping with other bevacizumab biosimilar PK studies and regulatory guidelines, area under the serum concentration–time curve extrapolated from 0 to infinity (AUC0-∞) was the primary PK parameter. Safety, tolerability and immunogenicity were also assessed

Of the 111 participants enrolled, 110 were included in the PK analysis (MYL 1402O, n = 37; EU-reference bevacizumab, n = 36; US-reference bevacizumab, n = 37) and all 111 were included in the safety analysis. All three bevacizumab formulations demonstrated similar mean serum concentrations and PK parameters. Natural log–transformed AUC0 ∞ comparisons all exhibited 90% confidence intervals within the predetermined 0.80 to 1.25 threshold for bioequivalence. Of 111 participants, 90 (81%) reported adverse events, with the most common being headache. Safety profiles and immunogenicity across all three treatments were comparable and all adverse events were mild or moderate in severity.

The authors concluded that overall, this study supports the bioequivalence of MYL 1402O to EU-reference bevacizumab and US-reference bevacizumab for PK and safety in healthy adult male volunteers. Results were generally consistent with previously published comparisons of bevacizumab biosimilars with reference biologicals and support continued investigation of MYL-1402O as a future, lower-cost alternative to reference bevacizumab.

In Europe, four bevacizumab biosimilars, including MYL 1402O, have been approved [4]. MYL 1402O was approved by the European Commission as Abevmy on 26 April 2021 [5]. FDA also accepted the application for the bevacizumab biosimilar MYL 1402O in March 2020 [6].

Conflict of interest
The authors of the research paper [3] reported conflict of interest, including being employees of Viatris or Biocon Research and being a consultant/advisory board member for Viatris. For full details of the authors’ conflict of interest, see the research paper [3].

Abstracted by Sandra Sposet, Account Director, MedThink, North Carolina, USA.

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References
1. GaBI Online - Generics and Biosimilars Initiative. Biosimilars approved in the US [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2021 Jul 30]. Available from: www.gabionline.net/Biosimilars/General/Biosimilars-approved-in-the-US 
2. GaBI Online - Generics and Biosimilars Initiative. Biosimilars of bevacizumab [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2021 Jul 30]. Available from: www.gabionline.net/Biosimilars/General/Biosimilars-of-bevacizumab 
3. Hummel M, Bosje T, Shaw A, et al. A pharmacokinetics study of proposed bevacizumab biosimilar MYL-1402O vs EU-bevacizumab and US-bevacizumab. J Cancer Res Clin Oncol 2021 [Epub ahead of print]. doi:10.1007/s00432-021-03628-0. 
4. GaBI Online - Generics and Biosimilars Initiative. Biosimilars approved in Europe [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2021 Jul 30]. Available from: www.gabionline.net/Biosimilars/General/Biosimilars-approved-in-Europe 
5. GaBI Online - Generics and Biosimilars Initiative. EC approves bevacizumab biosimilar Abevmy [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2021 Jul 30]. Available from: www.gabionline.net/Biosimilars/News/EC-approves-bevacizumab-biosimilar-Abevmy 
6. GaBI Online - Generics and Biosimilars Initiative. FDA accepts application for Mylan’s bevacizumab biosimilar [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2021 Jul 30]. Available from: www.gabionline.net/Biosimilars/News/FDA-accepts-application-for-Mylan-s-bevacizumab-biosimilar

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