1. Population Pharmacokinetics of MYL-1402O, a Proposed Biosimilar to Bevacizumab and Reference Product (Avastin®) in Patients with Non-squamous Non-small Cell Lung Cancer
- Date: Oct 4th, 2023
- Authors: Joel S. Owen, Russell J. Rackley, Matthew A. Hummel, Stefan Roepcke, Hannah Huang, Mark Liu, Tazeen A. Idris, Sundara Moorthi Nainar Murugesan, Ashwani Marwah, Subramanian Loganathan, Gopinath Ranganna, Abhijit Barve, Cornelius F. Waller & Mark A. Socinski
Abstract –
Background and Objectives: MYL-1402O is a bevacizumab (Avastin®) biosimilar. Pharmacokinetic and safety similarity of MYL-1402O and reference Avastin® authorized in the European Union (EU-Avastin®) and the US (US-Avastin®) was demonstrated in healthy subjects (phase I, NCT02469987). The key objectives of this study were to establish a population pharmacokinetic (PopPK) model on pooled data from the phase I and phase III clinical studies to assess pharmacokinetic linearity of MYL-1402O and Avastin® across dose ranges, to assess the pharmacokinetic similarity of MYL-1402O and Avastin® in patients with non-squamous non-small cell lung cancer (nsNSCLC), and to explore potential covariates to account for systematic sources of variability in bevacizumab exposure.
Methods:Efficacy and safety of MYL-1402O compared with EU-Avastin® was investigated in a multicenter, double-blind, randomized, parallel-group study in patients with stage IV nsNSCLC (phase III, NCT04633564). PopPK models were developed using a nonlinear mixed effects approach (NONMEM® 7.3.0).
Results: The pharmacokinetics of Avastin® and MYL-1402O were adequately described with a two-compartment linear model. Fourteen covariates were found to be statistically significant predictors of bevacizumab pharmacokinectics. The impact of each covariate on area under the concentration-time curve, half-life, and maximum plasma concentration was modest, and ranges were similar between the treatment groups, MYL-1402O and EU-Avastin®, in patients with nsNSCLC. The pharmacokinectics of bevacizumab appeared to be linear.
Conclusions: PopPK analysis revealed no significant differences between pharmacokinetics of MYL-1402O and Avastin® in patients with nsNSCLC. The developed PopPK model was considered robust, as it adequately described bevacizumab pharmacokinetics in healthy participants and nsNSCLC patients.
Conflict of Interest Statement: JO, SR, HH are consultants from Simulation Plus Inc. for Viatris for Pharmacometric analyses. MS; Research/grant funding from Spectrum, Novartis, Lilly, Genentech, and AstraZeneca; speaker bureau for Genentech, AstraZeneca, Guardant, Bristol Myers Squibb, Novartis, and Bayer. CW: Member of advisory board of Viatris. RR, MH, ML, TI, GR, AB: Full time employees of Viatris and may hold stock of Viatris. AM, SL, SN: Full time employees of Biocon and may hold stock of Biocon
