Johnson & Johnson announced findings from the Phase 2 DAHLIAS study published in The Lancet showing that nipocalimab, an investigational FcRn treatment for Sjögren's disease (SjD), significantly decreased disease activity and severity in patients with moderate-to-severe disease. The study met its primary endpoint, with statistically significant improvement in ClinESSDAI score at Week 24 in the nipocalimab 15 mg/kg Q2W group compared to placebo (least squares mean difference −2.65; 90% confidence interval −4.03 to −1.28; p=0.0018).
Clinical Efficacy and Biomarker Improvements
The DAHLIAS study demonstrated reductions in disease activity supported by favorable changes in key biomarkers when compared to placebo, including lower levels of rheumatoid factor, fewer circulating immune complexes, and decreased inflammatory markers. This significant reduction in disease activity suggests nipocalimab may lessen the burden of SjD symptoms for patients impacted by the condition.
Patients who received nipocalimab reported a decrease in symptoms, with numerical improvements compared with placebo in the hallmark symptoms of SjD including dryness of the mouth, eyes, and/or vagina, as well as fatigue and joint pain. Additionally, an improvement in objective salivary flow (at least 50% increase from baseline) was observed in more than twice as many patients in the high dose nipocalimab group (15 mg/kg) compared to the placebo group (33% vs. 16%, respectively) at Week 24.
Safety Profile and Immune Function Preservation
Nipocalimab had a tolerable safety profile and no new safety signals were observed during the 24-week treatment period. Immune function was preserved throughout treatment, even among patients who experienced significant reductions in circulating immunoglobulin G (IgG) levels. There was no observed increase in serious infections and no participants required intravenous immunoglobulin (IVIG) or rescue therapy. The DAHLIAS data are consistent with the overall safety profile of IMAAVY™ (nipocalimab-aahu), which is approved in generalized myasthenia gravis (gMG).
Expert Commentary and Clinical Significance
"The DAHLIAS Phase 2 study represents an important step forward in the understanding of FcRn inhibition as a potential therapeutic approach in Sjögren's disease. By demonstrating clinically meaningful improvements in disease activity and reductions in key biological indicators, nipocalimab may offer an avenue for addressing the autoantibody-driven pathology of this complex condition," said Ghaith Noaiseh, M.D., Associate Professor, Allergy, Clinical Immunology, and Rheumatology, The University of Kansas Medical Center. "The ability of nipocalimab to potentially lower IgG autoantibody levels rapidly and reversibly is consistent with the mechanism of FcRn inhibition and does so without broadly suppressing the immune system."
Regulatory Status and Development Program
Nipocalimab is the only investigational treatment to be granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration (FDA) for SjD in November 2024. It also received Fast Track Designation by the U.S. FDA in April 2025. Building on the regulatory momentum, the Phase 3 DAFFODIL study is now underway and actively enrolling patients.
The drug has received multiple regulatory designations across various indications, including U.S. FDA Fast Track designation for hemolytic disease of the fetus and newborn (HDFN), warm autoimmune hemolytic anemia (wAIHA), gMG, and fetal and neonatal alloimmune thrombocytopenia (FNAIT). It also holds U.S. FDA Orphan drug status for several conditions and Breakthrough Therapy designation for HDFN.
Study Design and Patient Population
DAHLIAS (NCT04968912) is a Phase 2 multicenter, randomized, placebo-controlled double-blind, dose-ranging study to evaluate the effects of nipocalimab in participants with moderately-to-severely active primary SjD who were seropositive for anti-Ro60 and/or anti-Ro52 immunoglobulin G (IgG) antibodies. The study enrolled 163 adults aged 18-75 who were randomized 1:1:1 to receive intravenous nipocalimab at 5 or 15 mg/kg, or placebo every 2 weeks through Week 22. The primary endpoint was change from baseline in the ClinESSDAI (Clinical European League Against Rheumatism Sjögren's Syndrome Disease Activity Index) Score at Week 24.
Disease Background and Unmet Medical Need
"A significant unmet need exists in the treatment of Sjögren's disease, a condition in which patients, 9 out of 10 of which are women, live with persistent and often debilitating symptoms, yet there are no approved therapies available," said Leonard L. Dragone, M.D., Ph.D., Disease Area Leader, Rheumatology and Autoantibody, Johnson & Johnson Innovative Medicine.
Sjögren's disease is one of the most prevalent autoantibody-driven diseases for which no therapies are currently approved that treat the underlying and systemic nature of the disease. It is a chronic autoimmune disease that is estimated to impact approximately four million people worldwide and is nine times more common in women than men. SjD is characterized by autoantibody production, chronic inflammation, and lymphocytic infiltration of exocrine glands. More than 50% of SjD patients have a moderate to severe form of the condition, and disease burden can be as high as that of rheumatoid arthritis or systemic lupus erythematosus.
