Background
Phase 2/3, randomised, double-blind, 24-week study of nipocalimab, an immunoselective neonatal Fc receptor (FcRn) blocker that lowers circulating IgG (including pathogenic autoantibodies), in warm autoimmune hemolytic anemia (wAIHA) — a rare, life-threatening disease with no approved therapies. 115 participants randomised: nipocalimab 30 mg/kg IV q4w (n=38), 15 mg/kg IV q2w (n=38), or placebo (n=39).
Results
Interventions and follow up: Arm A: Nipocalimab 30 mg/kg IV every 4 weeks.
Arm B: Nipocalimab 15 mg/kg IV every 2 weeks.
Arm C: Placebo.
Primary endpoint: durable hemoglobin response (Hb ≥10 g/dL and ≥2 g/dL increase from baseline at 3 consecutive visits ≥28 days apart, starting by Week 16, without rescue therapy).
mFollow up: 24 weeks (double-blind period).
Results: Durable Hb response: 23.7% (9/38) nipocalimab 30 mg/kg q4w vs 7.7% (3/39) placebo; 1-sided P=.015 (met). 15 mg/kg q2w 21.1% (8/38); P=.044 (not significant per hierarchy).
FACIT-Fatigue improvement (Wk 24): +3.4 (30 mg/kg; nominal P=.007) vs +0.6 placebo.
Mean prednisone dose reduction: 15.1% (30 mg/kg; nominal P=.039) vs 3.9% placebo.
Arm B: Nipocalimab 15 mg/kg IV every 2 weeks.
Arm C: Placebo.
Primary endpoint: durable hemoglobin response (Hb ≥10 g/dL and ≥2 g/dL increase from baseline at 3 consecutive visits ≥28 days apart, starting by Week 16, without rescue therapy).
mFollow up: 24 weeks (double-blind period).
Results: Durable Hb response: 23.7% (9/38) nipocalimab 30 mg/kg q4w vs 7.7% (3/39) placebo; 1-sided P=.015 (met). 15 mg/kg q2w 21.1% (8/38); P=.044 (not significant per hierarchy).
FACIT-Fatigue improvement (Wk 24): +3.4 (30 mg/kg; nominal P=.007) vs +0.6 placebo.
Mean prednisone dose reduction: 15.1% (30 mg/kg; nominal P=.039) vs 3.9% placebo.
Adverse events
Overall: safety consistent with the known nipocalimab profile and wAIHA-associated risks; no new safety signals over 24 weeks.
Grade ≥3 / infections / discontinuation: NR in the primary report.
Grade ≥3 / infections / discontinuation: NR in the primary report.
Conclusions
In the first randomised controlled trial in wAIHA, nipocalimab 30 mg/kg q4w met its primary endpoint for durable hemoglobin response, with nominal improvements in fatigue and steroid-sparing and no new safety signals. FcRn blockade is a promising targeted approach in a disease with no approved treatments.
Key Limitations
Absolute response was modest (23.7% vs 7.7%); the 15 mg/kg q2w dose missed significance, and the fatigue and steroid-reduction endpoints were nominal only. Small, rare-disease population over a short 24-week double-blind window; durability, transfusion independence, and long-term safety of sustained IgG lowering (infection risk) require longer follow-up. No active comparator.
Clinical Context
wAIHA management currently relies on off-label corticosteroids, rituximab, and splenectomy, with no FDA- or EMA-approved agents. ENERGY positions nipocalimab (in development across other IgG-mediated diseases) as a potential first approved targeted therapy for wAIHA; regulatory filing/decision NR. NCT04119050.