FcRn blocker nipocalimab: A new treatment option for systemic lupus erythematosus?

The neonatal Fc receptor (FcRn)  blocker nipocalimab, already approved for myasthenia gravis, showed promising results in a proof-of-concept phase 2 trial in systemic lupus erythematosus (SLE). By lowering immunoglobulin G (IgG) levels, the drug aims to reduce the pathogenetic autoantibodies that drive the disease.

IgG antibodies contribute to inflammation and tissue damage through direct binding to cellular targets and immune activation following tissue deposition of circulating immune complexes. As explained by Dr Richard Furie (Northwell Health, NY, USA), the rationale for using nipocalimab is that reducing circulating IgG levels should decrease these pathogenic autoantibodies, mirroring the drug’s mechanism of action in myasthenia gravis, for which nipocalimab was approved last year [1].

A phase 2 study randomised 221 patients in a 1:1:1 ratio to receive placebo or nipocalimab at 5 mg/kg or 15 mg/kg, administered every 2 weeks. Participants had relatively long-standing disease and high disease activity despite standard therapy. Treatment continued for 52 weeks, with Systemic Lupus Erythematosus Responder Index-4 (SRI-4) composite response as the primary endpoint.

The study demonstrated clear efficacy. SRI-4 responses were achieved by 54% and 52% of patients receiving the high and low nipocalimab doses, respectively. Although a pronounced placebo response was observed, with 40% of placebo-treated patients achieving SRI-4, the difference between placebo and the high-dose group was statistically significant. Efficacy was also evaluated in 3 prespecified biomarker-defined populations based on nipocalimab’s mechanism of action.

A subgroup of patients with particularly high autoantibody signatures appeared to derive the greatest benefit, with SRI-4 response rates of 76% and 66% in the high- and low-dose groups, respectively, compared with 11% in the placebo group, although this subgroup represented only 15% of the study population. Achievement of lupus low disease activity state (LLDAS) was likewise influenced by biomarker status: at week 52, 38% of patients receiving high-dose therapy achieved LLDAS, compared with 54% in the high-autoantibody subgroup. Both autoantibody levels and circulating immune complexes decreased throughout the treatment period.

The safety profile was reassuring. Infection rates were comparable across the treatment groups, with no unexpected safety findings. In the highest-dose group, IgG concentrations decreased to below 3 g/L in some patients; however, Dr Furie reported that none of these participants experienced serious adverse events.

A phase 3 trial is now underway to confirm these early findings.

1. Furie R, et al. Nipocalimab in SLE: First-in-class efficacy and safety results demonstrating proof of concept for FcRn blockade from the phase 2 JASMINE-SLE study. LB0007, EULAR 2026, 3–6 June, London, United Kingdom.