PHARMACODYNAMIC EFFECT OF NIPOCALIMAB IN WARM AUTOIMMUNE HEMOLYTIC ANEMIA (WAIHA) AND CORRELATION WITH CLINICAL IMPROVEMENT
8 affiliations
- 1Hematology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
- 2Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY, United States
- 34The University of Osaka, Suita, Osaka, Japan
- 4Department of Hematology and Amsterdam Institute for Infection and Immunity, Amsterdam UMC, University of Amsterdam; Department of Immunohematology Diagnostics, Sanquin Diagnostics Services, Amsterdam, Netherlands
- 5Johnson & Johnson, Cambridge, MA, United States
- 6Johnson & Johnson, Spring House, PA, United States
- 7Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
- 8Hospital das Clínicas da Universidade Federal de Goias (HC UFG), Goiania, GO, Brazil
Abstract
Background: Warm autoimmune hemolytic anemia (wAIHA) is a rare, potentially life-threatening disease characterized by autoantibody (typically IgG)-mediated premature destruction of red blood cells (RBCs). Nipocalimab is a fully human monoclonal antibody that binds FcRn with high specificity and affinity to block the IgG-recycling pathway, thus lowering total IgG (including pathogenic anti-RBC IgG autoantibodies) without impacting other key humoral and cellular immune functions. Aim: This analysis characterized the pharmacodynamic (PD) effect of nipocalimab on total IgG and anti-RBC IgG and the correlation with the change in hemoglobin (Hgb) and hemolytic markers during the 24-week double blind (DB) period of the phase 2/3 ENERGY trial (ClinicalTrials.gov Identifier: NCT04119050). Methods: Adults with wAIHA (Hgb <10 g/dL, laboratory evidence of hemolysis, and positive direct antiglobulin test) who received ≥1 prior therapy and consented to participate were randomized 1:1:1 to intravenous nipocalimab 30 mg/kg q4w, 15 mg/kg q2w, or placebo. Serum total IgG and anti-RBC IgG levels were measured in the DB period, and percent change from baseline was determined at all timepoints with available samples. Total IgG was measured with an immunonephelometric assay at a central lab. A semiquantitative multiplex flow cytometry based-assay was used to measure binding of anti-RBC IgG at 37oC to 12 reference RBC populations (representing warm autoantibodies pathogenic in wAIHA). The median percent change values for all positive reference RBC types were used to represent the overall percent change in anti-RBC IgG. Spearman correlations of change in total and anti-RBC IgG levels with changes in Hgb and hemolytic markers (ie, reticulocyte counts, indirect bilirubin) were determined. Results: Of the 118 patients in the ENERGY trial, 114 were included in the total IgG analysis (38, 37, and 39 in nipocalimab 30 mg/kg q4w, 15 mg/kg q2w, and placebo groups, respectively) and 89 were included in the anti-RBC IgG analysis (30, 31, and 28 in nipocalimab 30 mg/kg q4w, 15 mg/kg q2w, and placebo groups, respectively) based on patient consent and sample availability. Baseline clinical characteristics for individuals in the PD analysis set were similar between treatment groups and to those of the overall study population. Rapid and persistent reduction in total IgG was observed from Week 1 (W1) through W24 in the nipocalimab groups. Similarly, rapid and persistent reduction in anti-RBC IgG was observed in nipocalimab treatment groups, with consistent trends across the 12 reference RBC types. The median overall reduction in anti-RBC IgG was 41% and 35% at W1 and 23% and 16% at W24 for the 30 mg/kg q4w and 15 mg/kg q2w groups, respectively. Correlations were observed between total IgG reduction and Hgb improvement (R=-0.22; p<0.0001) as well as anti-RBC IgG reduction and Hgb improvement (R=-0.33, p<0.0001). In addition, anti-RBC IgG reduction was correlated with improvement in hemolytic markers. Conclusion: Nipocalimab reduced both total IgG as well as pathogenic anti-RBC IgG autoantibodies in wAIHA, supporting its mechanism of action as an FcRn blocker. A correlation was observed between anti-RBC IgG reduction and improvement in disease biomarkers, most notably increase in Hgb, consistent with nipocalimab targeting autoantibody-mediated disease mechanisms in wAIHA.
Related
- ASSESSMENT OF NIPOCALIMAB EFFECTS ON FATIGUE IN WARM AUTOIMMUNE HEMOLYTIC ANEMIA: RESULTS FROM THE DOUBLE-BLIND PHASE 2/3 ENERGY TRIAL
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- Clonal hematopoiesis in autoimmune hemolytic anemia
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BibTeX
@article{fattizzo2026pharmacodynamic,
title = {{PHARMACODYNAMIC EFFECT OF NIPOCALIMAB IN WARM AUTOIMMUNE HEMOLYTIC ANEMIA (WAIHA) AND CORRELATION WITH CLINICAL IMPROVEMENT}},
author = {Bruno FATTIZZO and Irina MURAKHOVSKAYA and Yasutaka UEDA and Josephine M I VOS and Eugene MYSHKIN and Vani LAKSHMINARAYANAN and Kristen BROWN and Leona E LING and Emile VAN DEN AKKER and Kerly FU and Cathye SHU and Kristen SWEET and Carolyn A CUFF and Sheng GAO and Marcia T SANTOS and Renato S TAVARES},
journal = {Hematology, Transfusion and Cell Therapy},
year = {2026},
month = oct,
doi = {10.1016/j.htct.2026.106690},
url = {https://doi.org/10.1016/j.htct.2026.106690},
note = {CC BY},
}
RIS
TY - JOUR
TI - PHARMACODYNAMIC EFFECT OF NIPOCALIMAB IN WARM AUTOIMMUNE HEMOLYTIC ANEMIA (WAIHA) AND CORRELATION WITH CLINICAL IMPROVEMENT
AU - Bruno FATTIZZO
AU - Irina MURAKHOVSKAYA
AU - Yasutaka UEDA
AU - Josephine M I VOS
AU - Eugene MYSHKIN
AU - Vani LAKSHMINARAYANAN
AU - Kristen BROWN
AU - Leona E LING
AU - Emile VAN DEN AKKER
AU - Kerly FU
AU - Cathye SHU
AU - Kristen SWEET
AU - Carolyn A CUFF
AU - Sheng GAO
AU - Marcia T SANTOS
AU - Renato S TAVARES
PY - 2026
DA - 2026/10/23
JO - Hematology, Transfusion and Cell Therapy
DO - 10.1016/j.htct.2026.106690
UR - https://doi.org/10.1016/j.htct.2026.106690
AB - Background: Warm autoimmune hemolytic anemia (wAIHA) is a rare, potentially life-threatening disease characterized by autoantibody (typically IgG)-mediated premature destruction of red blood cells (RBCs). Nipocalimab is a fully human monoclonal antibody that binds FcRn with high specificity and affinity to block the IgG-recycling pathway, thus lowering total IgG (including pathogenic anti-RBC IgG autoantibodies) without impacting other key humoral and cellular immune functions. Aim: This analysis characterized the pharmacodynamic (PD) effect of nipocalimab on total IgG and anti-RBC IgG and the correlation with the change in hemoglobin (Hgb) and hemolytic markers during the 24-week double blind (DB) period of the phase 2/3 ENERGY trial (ClinicalTrials.gov Identifier: NCT04119050). Methods: Adults with wAIHA (Hgb <10 g/dL, laboratory evidence of hemolysis, and positive direct antiglobulin test) who received ≥1 prior therapy and consented to participate were randomized 1:1:1 to intravenous nipocalimab 30 mg/kg q4w, 15 mg/kg q2w, or placebo. Serum total IgG and anti-RBC IgG levels were measured in the DB period, and percent change from baseline was determined at all timepoints with available samples. Total IgG was measured with an immunonephelometric assay at a central lab. A semiquantitative multiplex flow cytometry based-assay was used to measure binding of anti-RBC IgG at 37oC to 12 reference RBC populations (representing warm autoantibodies pathogenic in wAIHA). The median percent change values for all positive reference RBC types were used to represent the overall percent change in anti-RBC IgG. Spearman correlations of change in total and anti-RBC IgG levels with changes in Hgb and hemolytic markers (ie, reticulocyte counts, indirect bilirubin) were determined. Results: Of the 118 patients in the ENERGY trial, 114 were included in the total IgG analysis (38, 37, and 39 in nipocalimab 30 mg/kg q4w, 15 mg/kg q2w, and placebo groups, respectively) and 89 were included in the anti-RBC IgG analysis (30, 31, and 28 in nipocalimab 30 mg/kg q4w, 15 mg/kg q2w, and placebo groups, respectively) based on patient consent and sample availability. Baseline clinical characteristics for individuals in the PD analysis set were similar between treatment groups and to those of the overall study population. Rapid and persistent reduction in total IgG was observed from Week 1 (W1) through W24 in the nipocalimab groups. Similarly, rapid and persistent reduction in anti-RBC IgG was observed in nipocalimab treatment groups, with consistent trends across the 12 reference RBC types. The median overall reduction in anti-RBC IgG was 41% and 35% at W1 and 23% and 16% at W24 for the 30 mg/kg q4w and 15 mg/kg q2w groups, respectively. Correlations were observed between total IgG reduction and Hgb improvement (R=-0.22; p<0.0001) as well as anti-RBC IgG reduction and Hgb improvement (R=-0.33, p<0.0001). In addition, anti-RBC IgG reduction was correlated with improvement in hemolytic markers. Conclusion: Nipocalimab reduced both total IgG as well as pathogenic anti-RBC IgG autoantibodies in wAIHA, supporting its mechanism of action as an FcRn blocker. A correlation was observed between anti-RBC IgG reduction and improvement in disease biomarkers, most notably increase in Hgb, consistent with nipocalimab targeting autoantibody-mediated disease mechanisms in wAIHA.
SN - 2531-1379
SN - 2531-1387
ER -