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

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.