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ABSTRACT
Background: PF-06438179/GP1111 (PF-SZ-IFX) is an infliximab (IFX) biosimilar. Pharmacokinetic (PK) similarity of PF-SZ-IFX and reference IFX authorized in the European Union (ref-IFX-EU) and in the US (ref-IFX-US) was demonstrated in healthy subjects. Safety and efficacy of PF-SZ-IFX were investigated in a multinational, double-blind, randomized study in rheumatoid arthritis (RA) patients. This work aims to evaluate the population pharmacokinetics (PopPK) of ref-IFX-EU and PF-SZ-IFX in RA patients.
Research design and methods: Patients with moderately to severely active RA (N = 650) were randomized 1:1 to PF-SZ-IFX or ref-IFX-EU. PopPK modeling with data collected from the study was performed using a nonlinear mixed-effects approach (NONMEM 7.2.0).
Results: The PK of ref-IFX-EU and PF-SZ-IFX were adequately described using a two-compartment model with linear elimination. Clearance (CL) estimates were 0.014 L/h and 0.015 L/h for PF-SZ-IFX and ref-IFX-EU, with inter-individual variability (IIV) on CL of 43.1% and 40.1%, respectively. Volumes of distribution in the central compartment (V1) were 3.38 L and 3.57 L, with IIV on V1 of 28.1% and 23.7%, respectively. The same covariates of sex and antidrug antibody titers on CL, and body weight on V1, influenced the PK variability of ref-IFX-EU and PF-SZ-IFX.
Conclusions: PopPK analysis revealed no appreciable differences between the PK of ref-IFX-EU and PF-SZ-IFX in RA patients.
Trial registration: ClinicalTrials.gov identifier: NCT02222493.
Acknowledgments
Editorial support was provided by Iain McDonald, PhD, of Engage Scientific Solutions, and was funded by Pfizer Inc.
Author contributions
R Palaparthy, D Yin, and MI Rehman were involved in the study design, data collection and data analysis. O von Richter was involved in the data analysis. All authors were involved with the interpretation of data. All authors participated in drafting the manuscript and revising the manuscript critically for important intellectual content, and have given final approval of the version to be published. All authors agree to be accountable for all aspects of the work.
Availability of data
Upon request, and subject to certain criteria, conditions and exceptions (see https://www.pfizer.com/science/clinical-trials/trial-data-and-results for more information), Pfizer will provide access to individual de-identified participant data from Pfizer-sponsored global interventional clinical studies conducted for medicines, vaccines and medical devices (1) for indications that have been approved in the US and/or EU; or (2) in programs that have been terminated (i.e. development for all indications has been discontinued). Pfizer will also consider requests for the protocol, data dictionary, and statistical analysis plan. Data may be requested from Pfizer trials 24 months after study completion. The de-identified participant data will be made available to researchers whose proposals meet the research criteria and other conditions, and for which an exception does not apply, via a secure portal. To gain access, data requestors must enter into a data access agreement with Pfizer.
Declaration of interest
R Palaparthy, D Yin, and MI Rehman are employees of and hold stock in Pfizer Inc. O von Richter is an employee of Sandoz Biopharmaceuticals, Hexal AG (a Sandoz company). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Reviewer Disclosures
Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.
Supplementary material
Supplemental data for this article can be accessed here.