Nipocalimab - Effect on IgG Levels in Patients with Warm Autoimmune Hemolytic Anemia

SUMMARY

• The company cannot recommend any unapproved practices, procedures, or usage of nipocalimab.
• In a phase 2/3, randomized, double-blind (DB), placebo (PBO)-controlled trial in adult patients with warm autoimmune hemolytic anemia (wAIHA), nipocalimab was associated with reductions in total immunoglobulin (IgG) and anti-red blood cell (RBC) IgG.¹

CLINICAL DATA

Fattizzo et al (2026)¹ evaluated the pharmacodynamic effect of nipocalimab in adults with wAIHA in a phase 2/3 multicenter, randomized, DB, PBO-controlled study.

Study Design/Methods

• The study included adults (≥18 years of age) diagnosed with primary or secondary wAIHA for ≥3 months, defined as having all of the following:^1,2 
  • Hemoglobin (Hgb) <10 g/dL
  • Signs of hemolysis (lactic dehydrogenase [LDH] >upper limit of normal [ULN], or indirect bilirubin >ULN, or haptoglobin [Hp] <lower limit of normal [LLN])
  • Direct antiglobulin test (DAT) positive for IgG+/-complement component 3d (C3d)
• The study consisted of a 2-week screening phase, followed by a 24-week, DB, PBO-controlled treatment phase, a 144-week open-label extension (OLE) phase, and safety follow-up at 8 weeks after the last infusion.¹ 
• Eligible patients were randomized (1:1:1) to receive intravenous (IV) nipocalimab 
  30 mg/kg every 4 weeks (Q4W), nipocalimab 15 mg/kg every 2 weeks (Q2W), or PBO Q2W through week 24.
• Total IgG, Hgb, bilirubin levels, and reticulocyte counts were measured during the DB period.
• Pathogenic anti-RBC IgG levels were evaluated in a subset of patients.
  • In patients who received a rescue blood transfusion and/or IV immunoglobulins:
  • Before week 16: were excluded
  • After week 16: all data points after rescue treatment were excluded.
• Pathogenic anti-RBC IgG levels were evaluated in a subset of patients.
  • In patients who received a rescue blood transfusion and/or IV immunoglobulins:
    • Before week 16: were excluded
    • After week 16: all data points after rescue treatment were excluded
• The median percent change values across all reference RBC types with positive antibody binding at baseline were used to represent the overall percent change in pathogenic anti-RBC IgG.
• Last observation carried forward analysis was used to evaluate percent changes in total and anti-RBC IgG levels.

Results

• The total IgG analysis included 114 patients (nipocalimab 30 mg/kg Q4W, n=38;
  15 mg/kg Q2W, n=37; PBO, n=39).¹
• The anti-RBC IgG analysis included 89 patients (nipocalimab 30 mg/kg Q4W, n=30;
  15 mg/kg Q2W, n=31; PBO, n=28).
• For baseline demographics based on the pharmacodynamic analysis set, see Table: Baseline Demographic and Characteristics.

Total IgG Levels

• Total IgG reductions were observed with nipocalimab from week 1 through week 24.
• At week 1, the median total IgG reduction from baseline was 69% in the nipocalimab 30 mg/kg Q4W group and 60% in the nipocalimab 15 mg/kg Q2W group.
• At week 24, the median total IgG reduction from baseline was 33% in the nipocalimab 30 mg/kg Q4W group and 53% in the nipocalimab 15 mg/kg Q2W group. See Figure: Total IgG Levels over Time.

Pathogenic Anti-RBC IgG Autoantibody Levels

• Reductions in pathogenic anti-RBC IgG levels were observed in nipocalimab groups, with consistent trend across 12 reference RBC types.
• At week 1 and week 24, the median anti-RBC reduction from baseline was 41% and 23% in the nipocalimab 30 mg/kg Q4W group and 35% and 16% in the nipocalimab 15 mg/kg Q2W group, respectively. See Figure: Anti-RBC IgG Over Time

Correlations Between Changes in Hematologic Levels and Changes in Pathogenic Anti-RBC IgG Autoantibodies

• In the nipocalimab groups, changes for Hgb and pharmacodynamic biomarkers in opposite directions were observed. Specifically, in the nipocalimab 30 mg/kg Q4W group, alternating peaks and nadirs in total IgG were seen.
• In all patients included in the analysis, anti-RBC IgG reductions were correlated with improvement in Hgb (R=-0.33) and hemolytic markers, such as reticulocyte count (R=0.31) and indirect bilirubin levels (R=0.23). A correlation was also observed between total IgG reductions and Hgb improvement (R=-0.22).

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 22 June 2026.