Population pharmacokinetic, pharmacodynamic and efficacy modeling of SB12 (proposed eculizumab biosimilar) and reference eculizumab.

ABSTRACT:

Purpose

To describe, compare similarity of pharmacokinetic (PK), pharmacodynamic (PD) and efficacy of SB12 and reference eculizumab (ECU) and find clinically significant covariate relationships.

Methods

The PK, PD (terminal complement activity) and efficacy (LDH) data of SB12 and ECU were obtained from 289 subjects from phase I and phase III studies. One- and two-compartment PK models with first-order elimination were evaluated for SB12 and ECU. For PD and efficacy, both direct and indirect models were tested. The impact of covariates on PK, PD and efficacy parameters was assessed. Relationship between PK/PD and PD/efficacy was characterized. This modeling was performed using NONMEM version 7.4 (Icon Development Solutions, Ellicott City, MD, USA).

Results

The two-comp

SUBMITTER: Lee H 

PROVIDER: S-EPMC11303580 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature