Belatacept Pharmacokinetic Analysis of Belatacept Early Steroid Withdrawal Trial (BEST) to Clinical Outcomes and Compared With Reported BENEFIT and BENEFIT-EXT Pharmacokinetic Analysis

Abstract

Belatacept (BELA) pharmacokinetic (PK) studies informed dosing strategies used in phase 3 studies, where fixed mg/kg dosing compared a less intensive (LI) and more intensive (MI) regimen. The LI regimen was preferred due to a better risk/benefit profile. We compared PK parameters observed in the BELA Early Steroid Withdrawal Trial (BEST) with previous reports. BELA trough samples were analyzed using a validated quantitative enzyme-linked immunoassay. Clearance (CL) was estimated with Bayesian estimation using a published BELA population PK model. Significantly higher CL was observed in subjects <60 years old and African American (AA) patients, leading to decreased BELA exposure. No differences in allometrically scaled CL were observed by BMI or sex; however, overall BELA exposure was greater in males. There were no differences in exposure in subjects with rejection; however, subjects with infection had significantly higher exposure. BELA PK was not different between alemtuzumab and rabbit-antithymocyte globulin induction groups without steroids, but overall drug exposure was higher than previously reported in trials co-administering with basiliximab and steroids. Future studies to optimize BELA dosing strategies are warranted as BELA exposure in this analysis exceeded Phase 3 target thresholds. Trial Registration: ClinicalTrials.gov identifier: NCT01729494.