Nipocalimab - Effect on Fatigue in Patients with Warm Autoimmune Hemolytic Anemia

SUMMARY

• The company cannot recommend any unapproved practices, procedures, or usage of nipocalimab.
• ENERGY is a phase 2/3, multicenter, randomized, double-blind, placebo (PBO)-controlled trial in adult patients with warm autoimmune hemolytic anemia (wAIHA).¹
  • The mean change in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score from baseline to week 24 was 3.4 for nipocalimab 30 mg/kg intravenous (IV) every 4 weeks (Q4W), 1.2 for 15 mg/kg IV every 2 weeks (Q2W), and 0.6 for the PBO group.²

CLINICAL DATA

ENERGY STUDY

Fattizzo et al (2026)³ evaluated the efficacy and safety of nipocalimab in adults with wAIHA in a phase 2/3 multicenter, randomized, double-blind, PBO-controlled study.

Study Design/Methods

• The study included adults (≥18 years of age) diagnosed with primary or secondary wAIHA for ≥3 months, defined as having all of the following^1,3:
  • Hemoglobin (Hgb) <10 g/dL
  • Signs of hemolysis (lactic dehydrogenase [LDH] >upper limit of normal [ULN], or indirect bilirubin >ULN, or haptoglobin [Hp] <lower limit of normal [LLN])
  • Direct antiglobulin test (DAT) positive for immunoglobulin G (IgG) ± complement component 3d (C3d)
• The study consisted of a 2-week screening phase, followed by a 24-week, double-blind, PBO-controlled treatment phase, a 144-week open-label extension (OLE) phase, and safety follow-up at 8 weeks after the last infusion.
• Eligible patients were randomized (1:1:1) to receive IV nipocalimab 30 mg/kg Q4W, nipocalimab 15 mg/kg Q2W, or matching PBO Q2W through week 24.
• A key secondary endpoint was change from baseline to week 24 in patient-reported fatigue using the FACIT-Fatigue scale (score range 0-52 with higher scores indicating lesser fatigue and better overall functioning).²
  • The 13 item scale measures experience (feeling of fatigue; 5 items) and impact (daily functioning; 8 items), with a 7-day recall period.
  • A meaningful change threshold (MCT) for individual patient-level improvement was defined as a 6-point increase in the FACIT-Fatigue total score.
• Efficacy analyses were performed using the full analysis set (all randomized patients excluding 3 patients randomized to receive nipocalimab 30 mg/kg IV Q2W, a regimen which was subsequently discontinued).

Results

• The efficacy analysis population included 115 patients (nipocalimab 30 mg/kg IV Q4W, n=38; 15 mg/kg IV Q2W, n=38; and PBO, n=39).²

Fatigue

• The mean (interquartile range, IQR) FACIT-Fatigue total score at baseline was
  33.5 (27.0–43.0).
• Improvement in fatigue was observed as early as week 2 in patients receiving nipocalimab.
• The change in FACIT-Fatigue score from baseline to week 24 is depicted in the Figure: FACIT-Fatigue Score from Baseline to Week 24.

• The proportion of patients achieving a ≥6-point increase in MCT value is depicted in the figure: Proportion of Patients Achieving a ≥6-Point Increase in MCT Value.

• The correlation between change in FACIT-Fatigue total score and change in Hgb across all time points post-baseline is depicted in the Figure: Change in FACIT-Fatigue Total Score and Change in Hgb Across All Time Points.
  • Correlation with all treatment groups combined: across all time points (repeated measures, r=0.4353 and at week 24, r=0.3331.

• Changes in mean FACIT-Fatigue experience and impact subscales at week 24 are depicted in the Figure: Changes in Mean FACIT-Fatigue Experience and Impact Subscales at Week 24.

Safety

• Fatigue as an adverse event was reported in 10.3% of patients in the combined nipocalimab group.³

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 24 June 2026.