Nipocalimab shows stronger responses in Sjögren’s disease patients with high autoantibody levels
New Phase 2 analyses presented by Johnson & Johnson suggest that adults with moderate-to-severe Sjögren’s disease and elevated disease-driving autoantibodies may derive greater clinical benefit from nipocalimab, an investigational FcRn blocker currently being evaluated in a Phase 3 trial.
Johnson & Johnson has reported new exploratory analyses from its Phase 2 DAHLIAS study showing that adults with moderate-to-severe Sjögren’s disease who have elevated auto-antibody and immunoglobulin G (IgG) levels experienced greater clinical response rates with nipocalimab treatment.
The findings, which will be presented at the 2026 European Alliance of Associations for Rheumatology (EULAR) Congress, provide additional evidence supporting the role of pathogenic IgG autoantibodies in driving disease activity in certain patients with Sjögren’s disease. The analyses also strengthen the scientific rationale for nipocalimab, an investigational neonatal Fc receptor (FcRn) blocker designed to reduce disease-associated IgG autoantibodies while preserving broader immune function.
Why the findings matter
Sjögren’s disease is a chronic autoimmune condition characterised by substantial variability in symptoms and disease severity. According to Johnson & Johnson, patients with elevated autoantibody and IgG levels often experience a greater disease burden.
The latest analyses suggest that these patients may also be more likely to benefit from targeted reduction of pathogenic autoantibodies. The findings could help clinicians better understand which patient groups are most responsive to emerging therapies and contribute to ongoing efforts to develop treatments for a disease that remains underserved.
“Sjögren’s disease is a highly heterogeneous condition that has historically posed significant challenges for therapeutic development, leaving gaps in patient care,” said Dr R. Hal Scofield of the University of Oklahoma and the Oklahoma Medical Research Foundation.
“These analyses provide important insight into the potential role of pathogenic immunoglobulin G autoantibodies in disease activity and help expand our understanding of the biological drivers of Sjögren’s disease for certain patients,” Scofield said.
Greater responses seen in autoantibody-high subgroup
Johnson & Johnson said clinical improvements were observed across all participants in the DAHLIAS study. However, the strongest responses were seen among patients with elevated disease-driving autoantibodies and IgG levels.
Previously reported Phase 2 results showed that nipocalimab produced statistically significant improvements in ClinESSDAI scores compared with placebo.
In the latest analysis, 62.5% of patients in the autoantibody-high subgroup who received nipocalimab achieved a clinical response, compared with 51.9% in the overall study population treated with the drug.
The company said the findings support continued evaluation of nipocalimab as a potential immunoselective treatment approach for systemic Sjögren’s disease in the ongoing Phase 3 DAFFODIL study.
Biomarker data support proposed mechanism
Biomarker analyses from the study were consistent with the proposed mechanism of action of nipocalimab, according to the company.
Nipocalimab is designed to selectively reduce pathogenic IgG autoantibodies associated with Sjögren’s disease activity while preserving broader immune function. Autoantibodies are antibodies that mistakenly target the body’s own tissues and are considered important drivers of several autoimmune conditions.
“The biomarker analyses are consistent with the hypothesised mechanism of nipocalimab in Sjögren’s disease,” said Dr Leonard L. Dragone, Disease Area Leader, Autoantibody and Rheumatology at Johnson & Johnson.
“These findings suggest greater response in the broad study population of adults with moderate to severe SjD, plus a greater response observed among patients with elevated disease-driving autoantibodies and immunoglobulin G levels,” Dragone said.
He added that the data further advance understanding of the role pathogenic IgG autoantibodies may play in the disease as development of nipocalimab continues.
Regulatory status
Johnson & Johnson said nipocalimab is the only FcRn blocker to receive both Breakthrough Therapy Designation and Fast Track Designation from the U.S. Food and Drug Administration (FDA) for the treatment of adults with moderate-to-severe Sjögren’s disease.
The new findings add to previously reported evidence that nipocalimab may reduce disease activity and severity, including systemic manifestations and patient-reported symptoms such as dryness, fatigue and pain. Results from the ongoing Phase 3 DAFFODIL study are expected to provide further evidence on the therapy’s potential role in Sjögren’s disease management.
