{ "abstract": "Background: Warm autoimmune hemolytic anemia (wAIHA) is a rare, life-threatening disease characterized by autoantibody-mediated premature destruction of red blood cells. No treatments are currently approved for wAIHA. Nipocalimab is an immunoselective neonatal Fc receptor blocker that reduces circulating IgG levels, including autoantibodies. Aims: The phase 2/3, 24-week, double-blind ENERGY trial (NCT04119050) evaluated the efficacy and safety of intravenous nipocalimab in wAIHA. Methods: Adults with wAIHA (hemoglobin [Hgb] <10 g/dL, laboratory evidence of hemolysis, positive direct antiglobulin test) who received ≥1 prior therapy and consented to participate were randomized 1:1:1 to nipocalimab 30 mg/kg q4w, 15 mg/kg q2w, or placebo. Concomitant stable corticosteroids or immunosuppressants were allowed. Endpoints included durable Hgb response (primary; Hgb ≥10 g/dL and ≥2 g/dL increase from baseline at ≥3 consecutive visits [≥28 days] starting by Week 16 [W16], without rescue therapy or new/increased steroids/immunosuppressants), mean change from baseline in FACIT-Fatigue at W24, and % reduction in corticosteroid dose at W24 (mandatory taper for Hgb responders only). Multiplicity was controlled via an equal weight analysis, with one-sided α=0.02499; p-values were one-sided. Other endpoints included measures of hemolysis and safety. Results: A total of 115 participants were randomized to nipocalimab 30 mg/kg q4w (n=38), 15 mg/kg q2w (n=38) or placebo (n=39); at baseline, median (IQR) time from diagnosis was 2.7 (1.7‒5.0), 3.7 (1.7‒6.8) and 1.9 (1.4‒5.9) years and concomitant corticosteroids were used by 89%, 86% and 87%, respectively. Median (IQR) age was 57 (41‒72); 46% of participants were White, 55% were female, and 87% had primary wAIHA. Durable Hgb response was achieved by 24% (9/38) on nipocalimab 30 mg/kg q4w (p=0.015) and 21% (8/38) on 15 mg/kg q2w (p=0.044) versus 8% (3/39) on placebo. Mean Hgb increased by 1.1 g/dL at W1 on nipocalimab 30 mg/kg q4w and 0.7 g/dL on 15 mg/kg q2w versus -0.1 g/dL on placebo. Hgb level ≥10 g/dL and increase of ≥2 g/dL at ≥1 visit was achieved by 61% (23/38) on nipocalimab 30 mg/kg q4w (p<0.001) and 42% (16/38) on 15 mg/kg q2w (p=0.004) versus 15% (6/39) on placebo. FACIT-Fatigue improvement was observed from W2 to W24; at W24 (key secondary endpoint), mean (SD) improvement was 3.4 (7.3) for nipocalimab 30 mg/kg q4w (p=0.007) and 1.2 (6.1) for 15 mg/kg q2w (p=0.267) versus 0.6 (3.4) for placebo. The mean (SD) reduction in corticosteroid dose at W24 was 15% (28) for nipocalimab 30 mg/kg q4w (P=0.039) and 14% (30) for 15 mg/kg q2w (p=0.055) versus 4% (16) for placebo. Safety findings were consistent with nipocalimab’s known safety profile and wAIHA-associated risks. The proportion of patients with ≥1 adverse event (AE) was similar across groups (81%‒92%); common AEs (≥10% of patients on nipocalimab) included wAIHA, fatigue, diarrhea, asthenia, dizziness, headache, peripheral edema and pyrexia. Grade ≥3 infections were less frequent with nipocalimab 30 mg/kg q4w (5%) and 15 mg/kg q2w (8%) versus placebo (13%). Two deaths, both deemed not related to study drug, occurred in the nipocalimab 15 mg/kg q2w group. Conclusions: In wAIHA, nipocalimab 30 mg/kg q4w demonstrated rapid and durable efficacy in achieving the strict primary Hgb response with improvements in fatigue observed as early as W2, which was maintained over 24 weeks, with a favorable safety profile.", "abstract_shown": true, "affiliations": [ "Hematology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan; 2Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy", "Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY, United States", "The University of Osaka, Suita, Osaka, Japan", "Johnson & Johnson, Spring House, PA, United States", "Johnson & Johnson, Cambridge, MA, United States", "Johnson & Johnson, Raritan, NJ, United States", "Hospital das Clínicas da Universidade Federal de Goias (HC-UFG), Goiania, GO, Brazil" ], "article_type": null, "arxiv": null, "author_total": 12, "authors": [ { "affs": [ 0 ], "name": "Bruno FATTIZZO" }, { "affs": [ 1 ], "name": "Irina MURAKHOVSKAYA" }, { "affs": [ 2 ], "name": "Yasutaka UEDA" }, { "affs": [ 3 ], "name": "Doug SCHLICHTING" }, { "affs": [ 3 ], "name": "Kristen SWEET" }, { "affs": [ 3 ], "name": "Michael ZELASKY" }, { "affs": [ 3 ], "name": "Jagriti CRAIG" }, { "affs": [ 3 ], "name": "Jocelyn LEU" }, { "affs": [ 4 ], "name": "Leona LING" }, { "affs": [ 5 ], "name": "Sheryl PEASE" }, { "affs": [ 3 ], "name": "Cathye SHU" }, { "affs": [ 6 ], "name": "Renato S TAVARES" } ], "bibtex": "https://research.draconitic.com/paper/2n2ygaatvkwzb.bib", "cited_by": 0, "doi": "10.1016/j.htct.2026.106679", "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S2531137926004268", "id": "2n2ygaatvkwzb", "issns": [ "2531-1379", "2531-1387" ], "landing_url": "https://doi.org/10.1016/j.htct.2026.106679", "language": "en", "licence": "CC-BY", "licence_label": "CC BY", "licence_source": "journal", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "lcc", "RC633-647.5" ], [ "openalex", "2720|Blood groups and transfusion" ] ], "openalex": "W7223087065", "pdf_url": null, "pmcid": null, "pmid": null, "published": "2026-10-23", "publisher": "Elsevier", "ris": "https://research.draconitic.com/paper/2n2ygaatvkwzb.ris", "sources": [ { "first_seen": "2026-10-30T13:43:27Z", "native_id": "be8b54e247a04c3bbeab0696df234a9d", "source": "doaj", "url": "https://doi.org/10.1016/j.htct.2026.106679" } ], "subjects": [ { "field": "medicine", "origin": "lcc:RC633-647.5", "subfield": "endocrinology-metabolism" } ], "title": "NIPOCALIMAB FOR WARM AUTOIMMUNE HEMOLYTIC ANEMIA: RESULTS FROM THE PHASE 2/3 RANDOMIZED DOUBLE-BLIND ENERGY STUDY", "title_text": "NIPOCALIMAB FOR WARM AUTOIMMUNE HEMOLYTIC ANEMIA: RESULTS FROM THE PHASE 2/3 RANDOMIZED DOUBLE-BLIND ENERGY STUDY", "type": "peer-reviewed", "updated_at": "2026-10-30T13:43:27Z", "url": "https://research.draconitic.com/paper/2n2ygaatvkwzb", "venue": "Hematology, Transfusion and Cell Therapy", "versions": [] }