SUMMARY  

• The company cannot recommend any unapproved practices, procedures, or usage of nipocalimab.
• Nipocalimab is a fully human, aglycosylated, effectorless immunoglobulin G1 (IgG1) monoclonal antibody that binds with high affinity to the IgG-binding site on the neonatal Fc receptor (FcRn) and is being studied for the treatment of adult patients with primary Sjogren’s disease (SjD).^1,2
  • By selectively blocking FcRn, nipocalimab interferes with IgG recycling and in turn reduces circulating IgG levels, including pathogenic IgG autoantibodies that may contribute to primary SjD (those that target Ro/La ribonuclear complexes, ie, antibodies to primary SjD-associated antigen A [anti-Ro/SSA] and primary SjD-associated antigen B [anti-La/SSB]).³
• DAFFODIL is an ongoing phase 3, randomized, double-blind, placebo-controlled, multicenter study designed to evaluate the efficacy and safety of nipocalimab in adults with moderate to severe SjD. The results are not currently available. Details regarding the study status and study design of DAFFODIL can be found on clinicaltrials.gov and are summarized below.⁴
• DAHLIAS is a phase 2, multicenter, randomized, double-blind, placebo (PBO)-controlled trial evaluated the efficacy and safety of nipocalimab in adult patients with moderately to severely active primary SjD.^1,5
  • The primary endpoint was change from baseline in Clinical European League Against Rheumatism Sjogren’s Syndrome Disease Activity Index (ClinESSDAI) score at week 24. Patients treated with nipocalimab 15 mg/kg demonstrated statistically significant improvement in ClinESSDAI score from baseline to 24 weeks vs PBO (least square [LS] mean change: nipocalimab 15 mg/kg, -6.40 vs PBO, -3.74; P=0.0018).³
  • Nipocalimab treatment was well tolerated with no new safety signals observed.

BACKGROUND

• SjD is a chronic, autoimmune, systemic, progressive disease that can be associated with significant morbidity and mortality.¹
• SjD is characterized by lymphocytic infiltration of exocrine glands and B-cell dysfunction, resulting in sicca syndrome (dryness of the eye, oral cavity, pharynx, larynx, and/or vagina).^6,7 Ocular and oral dryness are the primary local manifestations, with >25% of patients also developing systemic symptoms.^7,8 Commonly affected organs include cardiovascular (Raynaud phenomenon), digestive (dysphagia, chronic gastritis), pulmonary (pleuritis), ocular (uveitis), cutaneous, neurological, eyes/nose/throat, and urological systems.⁸ SjD also increases the risk of hematologic malignancies in patients.^9,10
• SjD is classified into 2 categories^6,11:
  • Primary SjD: occurs by itself in an individual without underlying autoimmune disorder.
  • Secondary SjD: associated with other autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), or systemic sclerosis.
• Primary SjD has a global incidence of 6.92 (95% confidence interval [CI], 4.98-8.86) per 100,000 person-years at risk and a global prevalence of 60.82 (95% CI, 43.69-77.94) cases per 100,000 people.¹² It is more common in women than among men (incidence ratio, 9.15:1), with an average onset of 56.16 years of age (95% CI, 52.54-59.78).¹²
• Primary SjD develops from the activation of both innate and adaptive immune systems, triggered initially by viral infection of the salivary epithelial cells.^13,14 This leads to B-lymphocyte hyperactivity, resulting in abnormally high levels of IgG and production of pathogenic IgG autoantibodies specifically targeting Ro/La ribonuclear complexes (ie, anti-Ro/SSA and anti-La/SSB).^13,14 These pathogenic autoantibodies form immune complexes that activate inflammatory cascades, causing extraglandular tissue damage.¹³ Elevated B-cell activating factor levels are observed in the sera of patients with primary SjD and are upregulated in their salivary glands.¹⁵ Autoantibodies for rheumatoid factor, anti-Ro, and anti-La appear for a median of 4-6 years before symptom development.¹⁶ As the disease progresses, periductal infiltrate becomes more organized into ectopic lymphoid tissue, with an increase in the number of B-cells and formation of ectopic germinal centers.¹³
• Currently, there are no approved treatments to alter disease progression in SjD; thus, treatment strategies focus on symptomatic management.⁷ The Sjogren’s Syndrome Foundation has developed guidelines for assessing and managing dry eyes, dry mouth, and the systemic manifestations of SjD.^17-19

CLINICAL DATA

Phase 3 Study- DAFFODIL

DAFFOFIL⁴ is an ongoing phase 3, randomized, double-blind, placebo-controlled, multicenter study to assess the efficacy and safety of nipocalimab in adults with moderate to severe SjD.

Study Design/Methods

• Eligibility criteria of the DAFFODIL trial:
  • Adult patients (≥18 years of age) who are medically stable on physical examination, medical history, vital signs, clinical laboratory tests, and 12-lead electrocardiogram (ECG) performed at screening
  • Diagnosis of SjD as per 2016 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria
  • Seropositive for antibodies to Ro/SSA (Ro60 and/or Ro52)
  • Total Clinical European League Against Rheumatism Sjogren’s Syndrome Disease Activity Index (ClinESSDAI) score ≥5 at screening
  • For patients of childbearing potential must have a negative beta-hCG pregnancy test at screening and a negative urine pregnancy test at week 0 before randomization.
• Key exclusion criteria include:
  • History of severe, progressive and/or uncontrolled disorders such as hepatic, gastrointestinal, renal, pulmonary, cardiovascular, psychiatric, neurological, musculoskeletal, hypertension and autoimmune disorders or clinically significant abnormalities in screening laboratory
  • History of allergies, hypersensitivity, or intolerance to nipocalimab or its excipients or excipients used in the placebo formulation
  • Any confirmed or suspected clinical immunodeficiency syndrome not related to treatment of his/her SjD or has a history of congenital or hereditary immunodeficiency.
• A target of 600 eligible patients will be randomly assigned to subcutaneous (SC) nipocalimab+standard of care (SOC) and PBO+SOC treatments till week 48.
  • Eligible patients from both the treatment arms will enter an open-label extension phase and will continue to receive nipocalimab until week 143.
• Efficacy and safety will be evaluated through week 48. Please refer to Table: Study Objectives and Endpoints.

Phase 2 Study- DAHLIAS

Noaiseh et al (2025)³ assessed the efficacy and safety of nipocalimab in a phase 2, multicenter, randomized, double-blind, PBO-controlled trial in adult patients with moderately to severely active primary SjD.

Study Design/Methods

• Patients were permitted to receive background standard-of-care therapies, including immunomodulators, antimalarial drugs, or glucocorticoids, as allowed by the protocol.²⁰
• The study design is shown in Figure: Phase 2 Study Design (Primary SjD).

• Other key exploratory endpoints included pharmacokinetics and immunogenicity measures, clinical biomarkers, and pharmacodynamics.

Results

• A total of 163 patients were randomized to receive intravenous (IV) nipocalimab 5 mg/kg (n=53) or 15 mg/kg (n=54) or PBO (n=56) every 2 weeks (Q2W) through week 22.³
• Baseline characteristics were comparable between groups. For complete baseline demographics, see Table: Baseline Demographic Characteristics (Intent-To-Treat Population).

Efficacy

• A statistically significant change in ClinESSDAI from baseline was observed at week 24 for nipocalimab 15 mg/kg compared to PBO (P=0.0018).³
• Treatment with nipocalimab resulted in greater LS mean (90% CI) improvement from baseline to week 24 in the nipocalimab 5 mg/kg Q2W and 15 mg/kg Q2W groups when compared with PBO, as illustrated in Figure: LS Mean (90% CI) Change in ClinESSDAI at Week 24.

• Mean changes in secondary and supportive endpoints are presented in Tables: Secondary Endpoints and Supportive Endpoints.

Safety

• Overall, no cases of severe hypoalbuminemia (<20 g/L) or deaths were reported.
• Severe infections or infections requiring IV anti-infectives occurred in 3.8%, 1.9%, and 1.8% of participants in the nipocalimab 5 mg/kg, nipocalimab 15 mg/kg, and PBO groups, respectively, none of which were deemed related to the study treatment.
• For safety results, see Table: Nipocalimab Safety and Tolerability.

Pharmacokinetic (PK)/Pharmacodynamic (PD) Activity

• In a PK and PD simulation analysis, a 77% maximum reduction in total IgG was observed.²¹ 
  • Pre-dose (minimum) median reduction of 61% in total IgG was observed at week 24 in the nipocalimab 15 mg/kg group.
• Dose-dependent reductions from baseline in total IgG were observed with nipocalimab which returned to baseline levels by week 30.²²
  • Consistent reductions were observed in SjD-associated anti-Ro60, -Ro52, and -La IgG autoantibodies (see Table: Observed Predose (Minimum) Percent Change from Baseline in Clinical Biomarkers at Week 24).

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 18 February 2026.