SUMMARY  

• Nipocalimab is an investigational 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) that is being studied for the treatment of warm autoimmune hemolytic anemia (wAIHA) in adult patients.^1-3
  • By selectively blocking the FcRn, nipocalimab prevents IgG recycling and in turn lowers IgG levels, including pathogenic antibodies that are responsible for many autoimmune diseases such as wAIHA.
• An ongoing, phase 2/3, multicenter, randomized, double-blind, placebo-controlled study is evaluating the efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of nipocalimab vs placebo as an add-on to background standard-of-care (SOC) therapy for the treatment of patients with wAIHA (NCT04119050).^1,4

BACKGROUND

• wAIHA is the most prevalent type of autoimmune hemolytic anemia (AIHA), comprising approximately 60% of cases.⁵ It is characterized by the presence of autoantibodies (IgG or IgG+ C3d [final degradation product of the third component of complement, C3]⁶) that bind to red blood cell (RBC) antigens and prematurely destroy RBCs through hemolysis.^7,8 These autoantibodies and/or complement fragments on RBCs are detected by a direct antiglobulin test (DAT), also known as a direct Coombs test; although some patients with wAIHA may be DAT negative.⁸
• wAIHA is termed “warm” due to active antibodies causing hemolysis at body temperature (37°C).⁵ Clinical symptoms of wAIHA include fatigue, exertional dyspnea, dizziness, jaundice, and darkened urine, whereas laboratory findings include anemia, reticulocytosis, elevated lactate dehydrogenase and unconjugated bilirubin, and reduced haptoglobin.^8,9
• wAIHA is classified into 2 categories^7,10,11:
  • Primary wAIHA: no specific etiology identified and occurring in approximately half of the cases
  • Secondary wAIHA: primarily caused by underlying conditions, such as B-cell lymphoma, antiphospholipid syndrome, diabetes mellitus, systemic lupus erythematosus, rheumatoid arthritis, or chronic lymphocytic leukemia
• Currently, there are no approved treatments or established treatment guidelines for wAIHA. First-line treatment typically involves corticosteroids, such as prednisone or prednisolone; followed by subsequent lines of treatment, including rituximab, azathioprine, cyclophosphamide, and mycophenolate. Splenectomy is considered as a third-line treatment; however, about one-third of patients may experience a relapse after splenectomy. Blood transfusion is reserved for cases of severe symptomatic anemia and hemoglobin instability, particularly when the unsupported hemoglobin level falls below 8.0 g/dL.¹²

CLINICAL DATA

Phase 2/3 Study: ENERGY

A phase 2/3, randomized, placebo-controlled, double-blind, multicenter study (ENERGY) is currently evaluating the efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of nipocalimab vs placebo as an add-on to background SOC therapy for the treatment of patients with wAIHA.^4,13

Study Design/Methods

• The study aims to enroll approximately 111 patients to be randomized to receive intravenous nipocalimab at 2 different dose schedules or placebo.^1,2
• The study design is shown in Figure: ENERGY Study Design.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 04 December 2024.