Assessment of Nipocalimab Effects on Fatigue in Warm Autoimmune Hemolytic Anemia: Results From the Double-blind Phase 2/3 Energy Trial
Year: 2026
Type: article
Abstract: Background Warm autoimmune hemolytic anemia (wAIHA) is a rare, life-threatening disease characterized by autoantibody-mediated premature destruction of red blood cells (hemolysis). Patients with wAIHA frequently report fatigue and consider it to be a debilitating symptom associated with their diagnosis. There is currently a high unmet need for an effective treatment to address patients’ fatigue and other symptoms impacting health-related quality of life. Aims ENERGY trial (NCT04119050) data were analyzed to assess the impact of intravenous (IV) nipocalimab on fatigue in patients with wAIHA. Methods ENERGY is a phase 2/3 trial evaluating the efficacy and safety of IV nipocalimab in wAIHA. Adults 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 in the 24-week double-blind period. The primary endpoint was durable hemoglobin (Hgb) response (Hgb ≥10 g/dL and a Hgb increase of ≥2 g/dL for ≥3 consecutive visits [≥28 days], at or before Week 16 [W16]) without the need for rescue therapy. Fatigue was quantified by FACIT-Fatigue (key secondary endpoint), a content-valid patient-reported outcome measure that evaluates wAIHA-related fatigue (J Pat Rep Out. 2025;9(1):97) and single item Patient Global Impressions of Severity and Change (PGIS and PGIC) measures for fatigue. PGIS and PGIC data were used to determine the meaningful change threshold (MCT) for FACIT-Fatigue using anchor-based analysis. Correlation between Hgb and FACIT-Fatigue was examined. All analyses were prespecified. Results Participants were randomized to nipocalimab 30 mg/kg q4w (n=38), 15 mg/kg q2w (n=38) or placebo (n=39). Nipocalimab-treated participants reported rapid improvements in fatigue by W2 (first timepoint of assessment on treatment), measured by mean change from baseline in FACIT-Fatigue total score. Participants in the nipocalimab 30 mg/kg q4w group maintained improvements through W24. At W24, mean (SD) changes in FACIT-Fatigue total scores were 3.4 (7.3), 1.2 (6.1), and 0.6 (3.4) points for the nipocalimab 30 mg/kg q4w, 15 mg/kg q2w, and placebo groups, respectively; a positive correlation ( r =0.33) was observed between change from baseline in Hgb and FACIT-Fatigue. At W24, the nipocalimab 30 mg/kg q4w group had greater numerical mean improvements on the FACIT-Fatigue Experience (1.5) and Impact subscales (1.9) compared to placebo (0.2 and 0.4, respectively). The MCT in FACIT-Fatigue was determined to be 6 points; at W24, the MCT was achieved by 27%, 19%, and 5% of participants in the nipocalimab 30 mg/kg q4w, 15 mg/kg q2w, and placebo groups, respectively. A numerically greater percentage of nipocalimab-treated participants had improved PGIS fatigue severity (≥1-point) at W16, 20 and 24 compared to placebo. The percentage of participants reporting their fatigue on the PGIC to be “much better” at W24 compared to baseline was numerically greater in the nipocalimab-treated groups (38%, 12% and 9% for 30 mg/kg q4w, 15 mg/kg q2w, and placebo, respectively). Summary/Conclusion In the ENERGY trial, participants treated with nipocalimab reported early and prolonged improvements in fatigue, with the most consistent benefit observed with nipocalimab 30 mg/kg q4w. Fatigue improvement was supported by global patient assessments and showed a modest positive correlation with hemoglobin recovery, highlighting a patient-relevant benefit beyond correction of anemia. Support Johnson & Johnson.
Language: English
Topic: Blood groups and transfusion
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7223126271