A new study published in The Lancet has found that nipocalimab, a neonatal Fc receptor (FcRn) blocker, significantly reduces clinical disease activity in patients with moderate to severe active Sjögren’s disease. The findings mark a major step forward for a condition that currently lacks approved targeted or disease-modifying therapies.
Nipocalimab acts by blocking FcRn, a receptor that prolongs the survival of IgG antibodies, including harmful autoantibodies that drive autoimmune disease. By inhibiting the interaction between FcRn and IgG, the drug accelerates IgG breakdown, lowering levels of circulating IgG and pathogenic autoantibodies. The therapy is a fully human monoclonal IgG1 antibody engineered to minimize immune-mediated cytotoxicity. It has already shown benefit in disorders such as generalised myasthenia gravis and haemolytic disease of the fetus and newborn.
The phase 2 double-blind, multicentre trial enrolled 163 adults with active Sjögren’s disease between September 2021 and April 2023 across 69 centres in Europe, Asia, and the United States. All participants had a ClinESSDAI score of 6 or higher and were positive for anti-Ro IgG autoantibodies. The average age was 48 years, and women accounted for 93% of the cohort.
Participants were randomly assigned to receive nipocalimab 5 mg/kg, nipocalimab 15 mg/kg, or placebo intravenously every two weeks for 22 weeks. The primary endpoint was the change in ClinESSDAI score at week 24, excluding the biological domain to avoid confounding results related to IgG reduction.
The higher 15 mg/kg dose produced a significant improvement in disease activity, with a least squares mean difference of –2.65 compared with placebo (90% CI –4.03 to –1.28; p=0.0018). The 5 mg/kg dose showed a smaller, non-significant reduction. Safety outcomes were similar across all groups, with no major differences in adverse or serious adverse events.
This is the first known randomised controlled trial of an FcRn blocker in Sjögren’s disease and the largest study to use ClinESSDAI as the primary measure of efficacy. By lowering pathogenic IgG autoantibodies rather than targeting B-cell depletion, nipocalimab introduces a novel therapeutic approach for this chronic autoimmune condition.
The results provide clear proof of concept that reducing abnormal IgG autoantibodies may help control systemic Sjögren’s disease. The study reinforces interest in therapies that act on autoantibody-related pathways, offering hope for future disease-modifying options for patients who currently rely mainly on symptomatic management.
Reference
Noaiseh G, Sivils KL, Campbell K, Idokogi J, Lo KH, Liva SG, Leu JH, Dhatt H, Ma K, Leonardo S, Li H, Hubbard JJ, Gottenberg JE. Efficacy and safety of nipocalimab in patients with moderate-to-severe Sjögren’s disease (DAHLIAS): a randomised, phase 2, placebo-controlled, double-blind trial. Lancet. 2025 Nov 22;406(10518):2435-2448.