(M-088) PK/PD Analysis of the Primary Endpoint for Nipocalimab in Sjögren's Disease

Min Dong – Johnson & Johnson Innovative Medicine; Yuan Xiong – Johnson & Johnson Innovative Medicine; Fudan Zheng – Johnson & Johnson Innovative Medicine; Sophia Liva – Johnson & Johnson Innovative Medicine; Jocelyn Leu – Johnson & Johnson Innovative Medicine; An Vermeulen – Johnson & Johnson Innovative Medicine; Mahesh Samtani – Johnson & Johnson Innovative Medicine

Objectives: Nipocalimab is a fully human aglycosylated IgG monoclonal antibody (mAb) designed to selectively block the IgG binding site on endogenous neonatal Fc receptors (FcRn). This blockade reduces native IgG recycling, leading to decreased circulating IgG levels. Currently, nipocalimab is being investigated for several diseases with pathogenic IgG, including Sjögren's Disease (SjD), a systemic autoimmune disease characterized by elevated IgG levels affecting multiple organs and tissues. A randomized, placebo-controlled, double-blind, Phase 2 study was recently conducted to assess the PK, efficacy, and safety of nipocalimab treatment in adult patients with SjD (NCT04968912; Study SJD2001). The overall objective of the current analysis was to evaluate the relationship between IgG reduction and the primary clinical endpoint (clinESSDAI) from the Phase 2 study.

Methods: A total of 150 adult patients with confirmed primary SjD were enrolled to receive either a placebo or nipocalimab at doses of 5 mg/kg or 15 mg/kg IV Q2W. Population PK/PD modeling was first conducted to characterize nipocalimab PK and associated IgG reduction profiles. Subsequently, the current analysis was done to elucidate the longitudinal relationship between IgG reduction and clinESSDAI response.

Results: The total change in clinESSDAI scores from baseline was considered as the composite effect of placebo response and treatment effect. The placebo response was modeled as a linear function of time. An effect compartment was incorporated to account for the delay in clinESSDAI reduction relative to IgG changes and linked to clinESSDAI change over time through a linear relationship.
Covariate analysis identified that the individual baseline clinESSDAI score was a significant covariate for both the placebo response and the treatment effect. Model evaluation indicated that the model accurately described the time course of clinESSDAI reduction and its variability in patients. Model-based simulations suggested that a median clinESSDAI reduction of 4.4 can be achieved at Week 24, following the nipocalimab 15 mg/kg IV Q2W regimen.

Conclusions: A longitudinal PK/PD model was developed that adequately characterizes the relationship between IgG reduction and clinESSDAI changes in patients with SjD. This analysis represents one of the first PK/PD evaluations using clinESSDAI as the primary clinical endpoint for FcRn inhibitors in the treatment of SjD. Model-based simulations demonstrate the sustained clinESSDAI reduction following the 15 mg/kg IV Q2W regimen of nipocalimab in SjD participants, and will be used to inform dose selection in SjD patients for late-stage development.

Citations: None

Keywords: E-R analysis, immunology, nipocalimab, Sjögren's Disease (SjD)