Nipocalimab for Warm Autoimmune Hemolytic Anemia: Results From the Phase 2/3 Randomized Double-blind Energy Study
Year: 2026
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
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.
Language: English
Topic: Blood groups and transfusion
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7223087065