Pharmacokinetics, Pharmacodynamics, and Safety of Subcutaneous Belimumab in Pediatric Patients With Systemic Lupus Erythematosus: A Multicenter, Open-Label Trial.

Abstract

This study aimed to characterize the pharmacokinetics, pharmacodynamics, safety, and exploratory efficacy of subcutaneous belimumab in pediatric patients with active systemic lupus erythematosus (SLE) receiving standard therapy. This single-arm, multicenter, open-label trial (GSK study 200908; ClinicalTrials.gov identifier: NCT04179032) used three-weight-band subcutaneous dosing of belimumab 200 mg every week (qw) for pediatric patients weighing ≥50 kg, every 10 days for pediatric patients weighing 30 to <50 kg, and every 2 weeks (q2w) for pediatric patients weighing 15 to <30 kg. The pharmacokinetic profile was characterized by observed concentration at week 12 and population pharmacokinetics (popPK) estimates derived from concentrations over 52 weeks. Pharmacodynamics, safety, and exploratory efficacy (≥4-point reduction from the baseline Safety of Estrogens in Lupus Erythematosus National Assessment - Systemic Lupus Erythematosus Disease Activity Index [SELENA-SLEDAI] score) were descriptively evaluated. Alternative two-weight-band subcutaneous dosing (≥40 kg: 200 mg qw; 15 to <40 kg: 200 mg q2w) was simulated to predict pharmacokinetics for this regimen. Patients weighing 30 to <50 kg had lower observed belimumab concentrations than those weighing ≥50 kg (week 12 geometric mean 82.8 vs 134 μg/mL), but popPK analyses predicted the three weight bands to be generally consistent and in alignment with established adult subcutaneous and pediatric intravenous exposures. The pharmacodynamic and safety profile was consistent with known belimumab effects. By week 52, 18 of 22 patients (81.8%) had a ≥4-point reduction from baseline SELENA-SLEDAI scores. Hypothetical two-weight-band dosing simulations predicted consistent exposure across weight bands and in line with established exposures in SLE. Exposure following subcutaneous belimumab administration in pediatric patients is consistent with approved usage; these findings, along with consistent safety and efficacy data, support subcutaneous belimumab use for pediatric patients with SLE.