(S-008) Population PK-RO-IgG Modeling of Nipocalimab in Patients with Sjögren's Disease

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

Objectives: Nipocalimab is a fully human IgG1 monoclonal antibody designed to selectively block the IgG binding site on endogenous neonatal Fc receptors (FcRn), which inhibits IgG recycling and reduce circulating IgG levels. Sjögren’s disease (SjD) is an autoimmune disease associated with elevated IgG production and the presence of IgG autoantibodies. A Phase 2 DAHLIAS Study (80202135SJS2001, NCT04968912) was conducted to assess the efficacy and safety of nipocalimab in adults with SjD. The objective of this analysis was to characterize the relationship between nipocalimab PK, FcRn receptor occupancy and IgG reduction following IV administration in SjD patients from the DAHLIAS Study.

Methods: Previously, a population PK model and a PKPD model were developed using the clinical data from 4 Phase 1 studies in healthy participants to characterize the PK-RO-IgG relationship. The current PK-RO-IgG analyses were updated by integrating clinical data from the DAHLIAS Study in SjD patients. The pooled dataset included a total of 3667 nipocalimab concentrations, 1954 unoccupied receptor (%) records and 4743 IgG concentration records from 366 participants. The updated models were used to simulate nipocalimab concentrations and associated IgG reduction to inform dose selection for the next-stage of development in the SjD patient population.

Results: Nipocalimab PK exhibits significant nonlinear behavior. Along with RO, nipocalimab PK was adequately captured by a two-compartment quasi-steady state target-mediated drug disposition model following IV or SC doses. Body weight effects on clearances and volumes of distribution were included in the model using the standard allometric scaling approach. The longitudinal IgG data were adequately described by the indirect response model using a sequential modeling approach.1 The SjD population was added as a covariate on IgG baseline to account for the higher IgG baseline in SjD patients than in healthy participants. IgG simulation utilizing the updated PK-RO-IgG model shows that the 15 mg/kg IV Q2W regimen will substantially reduce IgG levels with an average lowering of 72%, pre-dose lowering of 63% and maximum lowering of 78% in the SjD population.

Conclusions: The updated PK-RO-IgG models adequately captured the time courses of both nipocalimab PK and total IgG in SjD patients. Model-based simulations demonstrate the extensive IgG lowering following 15 mg/kg IV Q2W regimen of nipocalimab in SjD patients, and will be used to inform dose selection for late-stage development.

Citations: [1] Taylor PC, Schett G, Huizinga TW, Wang Q, Ibrahim F, Zhou B, Liva SG, Shaik JSB, Xiong Y, Leu JH, Panchakshari RA, Loza MJ, Ma K, Dhatt H, Rojo Cella R, Karyekar CS, Cuff CA, Gao S, Fei K. Nipocalimab, an anti-FcRn monoclonal antibody, in participants with moderate to severe active rheumatoid arthritis and inadequate response or intolerance to anti-TNF therapy: results from the phase 2a IRIS-RA study. RMD Open. 2024 Jun 28;10(2):e004278.

Keywords: PKPD, IgG, nipocalimab