Population Pharmacokinetics of MYL-1402O, a Proposed Biosimilar to Bevacizumab and Reference Product (Avastin ® ) in Patients with Non-squamous Non-small Cell Lung Cancer.

Autor: Owen JS; Consulting Department, Cognigen Division of Simulations Plus, Buffalo, NY, USA. joel@pumas.ai., Rackley RJ; Global PK/DM Department, Viatris Inc, Morgantown, WV, USA., Hummel MA; Global PK/DM Department, Viatris Inc, Morgantown, WV, USA., Roepcke S; Pharmacometrics Department, Cognigen Division of Simulations Plus, Buffalo, NY, USA., Huang H; Pharmacometrics Department, Cognigen Division of Simulations Plus, Buffalo, NY, USA., Liu M; Global PK/DM Department, Viatris Inc, Morgantown, WV, USA., Idris TA; Global Clinical Sciences Department, Viatris, Hyderabad, India., Murugesan SMN; Clinical Development & Medical Affairs Department, Biocon Biologics Ltd, Bangalore, Karnataka, India., Marwah A; Clinical Development & Medical Affairs Department, Biocon Biologics Ltd, Bangalore, Karnataka, India., Loganathan S; Clinical Development & Medical Affairs Department, Biocon Biologics Ltd, Bangalore, Karnataka, India., Ranganna G; Global Clinical Sciences Department, Viatris, Bengaluru, India., Barve A; Clinical Development & Medical Affairs, Viatris Inc, Canonsburg, PA, USA., Waller CF; Department of Hematology, Oncology, and Stem Cell Transplantation, University Medical Centre Freiburg and Faculty of Medicine, Freiburg, Germany., Socinski MA; Cancer Institute, Advent Health Cancer Institute, Orlando, FL, USA.
Jazyk: angličtina
Zdroj: European journal of drug metabolism and pharmacokinetics [Eur J Drug Metab Pharmacokinet] 2023 Nov; Vol. 48 (6), pp. 675-689. Date of Electronic Publication: 2023 Oct 04.
DOI: 10.1007/s13318-023-00855-3
Abstrakt: 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.
(© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
Databáze: MEDLINE
Externí odkaz: