Nipocalimab - Clinical Studies in Systemic Lupus Erythematosus (SLE)

SUMMARY

• The company cannot recommend any unapproved practices, procedures, or usage of nipocalimab.
• Nipocalimab is a fully human immunoglobulin G (IgG) 1 monoclonal antibody that binds to the neonatal Fc receptor (FcRn). This results in the reduction of circulating IgG levels, including pathogenic IgG antibodies.¹
• GARDENIA is an ongoing phase 3, randomized, double-blind, placebo (PBO)-controlled, multicenter study designed to evaluate the efficacy and safety of nipocalimab in adult patients with moderate to severe systemic lupus erythematosus (SLE). The results are not currently available. Details regarding the study status and study design of GARDENIA are available on ClinicalTrials.gov and are summarized below.²
• JASMINE, a phase 2, multicenter, randomized, double-blind, PBO-controlled, parallel-group trial, evaluated the efficacy, safety, and pharmacodynamics (PD) of nipocalimab in adult patients with active SLE.³
  • The primary endpoint was the percentage of patients achieving SLE Responder Index-4 (SRI-4) composite response at week 24. Patients treated with nipocalimab 15 mg/kg showed a significant SRI-4 response of 53.5% vs 46.7% with PBO (P=0.081, with a prespecified 2-sided alpha level of 0.10 across doses). However, the endpoint was not met for the nipocalimab 5 mg/kg group.
  • Through week 58, adverse events (AEs) occurred in 89.6% (69/77) and 82.9% (63/76) of patients in the nipocalimab 5 mg/kg and 15 mg/kg groups, respectively vs 76% (57/75) in the PBO group.
  • Infections and infestation rates were reported at 58.4% (45/77) and 60.5% (46/76) of patients in the nipocalimab 5 mg/kg and 15 mg/kg groups, respectively vs 56% (42/75) the PBO group through week 58.

CLINICAL DATA

Phase 3 Study - GARDENIA

GARDENIA (NCT07438496)² is an ongoing phase 3, randomized, double-blind, PBO-controlled, multicenter study to assess the efficacy and safety of nipocalimab in adult patients with moderate to severe SLE.

Study Design/Methods

• Eligibility criteria of the GARDENIA trial:
  • Adult patients (18 to 75 years of age) who are medically stable on physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening
  • Diagnosis of SLE for ≥24 weeks prior to screening as per the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria
  • Must have a SLE Disease Activity Index 2000 (SLEDAI-2K) score ≥6 and a clinical SLEDAI-2K score ≥4 at screening, and clinical SLEDAI-2K score ≥4 at week 0, excluding points attributed to lupus headache, alopecia, and organic brain syndrome
  • Patients of childbearing potential must have a negative beta-human chorionic gonadotropin (β-hCG) pregnancy test at screening and a negative urine pregnancy test at week 0 before randomization
  • Presence of ≥ 1 British Isles Lupus Assessment Group (BILAG) A score or 2 BILAG B scores at screening
• Key exclusion criteria:
  • History of severe, progressive, and/or uncontrolled hypertension, hepatic, gastrointestinal, renal, pulmonary, cardiovascular, psychiatric, neurological, musculoskeletal, and/or autoimmune disorders or clinically significant abnormalities in screening laboratory.
  • Suspected or history of allergies, hypersensitivity, or intolerance to nipocalimab, its excipients, or excipients used in the PBO formulation
  • Any confirmed or suspected clinical immunodeficiency syndrome not related to SLE treatment, or 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) or PBO + SOC until week 52.
  • Eligible patients from both study groups will enter an open-label extension phase and continue to receive nipocalimab until week 156 or until discontinuation.
• Efficacy and safety will be evaluated through week 52. Please refer to Table: Study Objectives and Endpoints.

Phase 2 Study - JASMINE

Furie RA et al (2026)³ assessed the efficacy, safety, and PD of nipocalimab in a phase 2, multicenter, randomized, double-blind, PBO-controlled, parallel-group trial in adult patients with active SLE.

Study Design/Methods

• The total study duration was 64 weeks, including a ≤6-week screening period, a 52-week double-blind treatment period, and a 6-week follow-up period.
• The study design is shown in Figure: Phase 2 Study Design.

• The oral glucocorticoid (GC) taper schedule as follows:
  • Mandatory taper: from weeks 6-16 to a target of 7.5 mg/day and maintained through week 24
    • Patients on ≥10 mg/day oral GCs were required to taper; tapering could be paused or increased for disease worsening or safety concerns
  • Recommended taper: from weeks 24-40 to the target dose (7.5 mg/day) and maintained through week 52
• The primary efficacy and safety endpoints were evaluated by the full analysis set (FAS) population, defined as all randomized patients who received ≥1 dose of any study intervention.
• The major secondary efficacy endpoints were evaluated by the modified full analysis set (mFAS) population, defined as all randomized patients who received ≥1 dose of any study intervention, excluding 7 patients from one study site due to noncompliance with Good Clinical Practice.
• In the mFAS population, a predefined biomarker-based subpopulation was identified, and the patients were categorized into autoantibody (aAb)-positive, aAb-high and IFN-high.
  • aAb-positive population included patients positive ≥1 for anti-double stranded deoxyribonucleic acid (dsDNA), anti-Smith, or antinuclear antibody (ANA) with anti-ribonucleoprotein (RNP), anti-Ro, or historical anti-dsDNA.
  • aAb-high population included a subgroup of the aAb-positive population with increased circulating immune complex (CIC), high IFN signature, and low complement component 3 (C3). aAb population is identified through unsupervised consensus clustering based on semiquantitative baseline aAb intensities.
  • IFN-high population is defined using a peripheral blood ribonucleic acid (RNA) signature.

Results

• The FAS population of 228 patients were randomized to receive intravenous (IV) nipocalimab 5 mg/kg (n=77), 15 mg/kg (n=76), or PBO (n=75) every 2 weeks (Q2W) through week 52.
  • The mFAS population included 221 patients (nipocalimab 5 mg/kg, n=74; nipocalimab 15 mg/kg, n=74; PBO, n=73).
• For complete baseline demographics, see Table: Baseline Demographic Characteristics for the mFAS Population.

• In the mFAS population, predefined biomarkers were 79% of patients with aAb-positive, 15% of patients with aAb-high, and 66% of patients with IFN-high.

Efficacy

• At week 24, the primary efficacy endpoint, the percentages of patients achieving SRI-4 composite response, in nipocalimab 15 mg/kg vs PBO were 53.5% vs 46.7%, P=0.081 (controlled for multiplicity with a prespecified 2-sided α level of 0.10 across doses and evaluated based on the FAS population).
• For major secondary endpoints and the subpopulation analyses at week 52, see Table: Major Secondary Endpoints in the mFAS Population and the Predefined Biomarker-Based Subpopulation at Week 52.

Safety

• For safety results, see Table: Summary of Safety Endpoints through Week 58 in the FAS population.

• Through week 58, 2 cases of death were reported in patients from each nipocalimab treatment group due to septic shock. Both events were assessed by the investigator as unrelated to the study intervention.

PD Activity

• In PD analysis through week 52, nipocalimab reduced total IgG, CICs, and anti dsDNA and increased C3 levels, see Table: Pharmacodynamic Effects through Week 52 in the FAS Population.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 10 June 2026.