Nipocalimab for warm autoimmune hemolytic anemia: results from the phase 2/3 randomized, double-blind ENERGY study

Abstract

Warm autoimmune hemolytic anemia (wAIHA) is a rare, life-threatening disease characterized by autoantibody-mediated destruction of red blood cells with no approved treatments. Nipocalimab, an immunoselective neonatal Fc receptor blocker, reduces circulating IgG levels, including autoantibodies implicated in wAIHA. The phase 2/3, randomized, 24-week, double-blind ENERGY study in participants with wAIHA evaluated nipocalimab 30 mg/kg IV q4w (n=38), 15 mg/kg IV q2w (n=38), and placebo (n=39). The primary endpoint, durable hemoglobin response (hemoglobin ≥10 g/dL and a ≥2 g/dL increase from baseline at 3 consecutive visits [≥28 days] starting by Week 16, without rescue therapy), achieved statistical significance for nipocalimab 30 mg/kg IV q4w (23.7% [9/38]; 1-sided P=0.015) but not 15 mg/kg IV q2w (21.1% [8/38]; P=0.044; not significant) versus placebo (7.7% [3/39]). Improvement in FACIT-Fatigue score at Week 24 (key secondary endpoint) was observed with nipocalimab, with mean (SD) improvement of 3.4 (7.29) points (nominal P=0.007) for 30 mg/kg IV q4w and 1.2 (6.07) (nominal P=0.267) for 15 mg/kg IV q2w versus 0.6 (3.42) for placebo. Mean percent (SD) reduction in average daily prednisone dose (key secondary endpoint) was 15.1% (28.2) for nipocalimab 30 mg/kg IV q4w (nominal P=0.039) and 14.0% (30.4) for 15 mg/kg IV q2w (nominal P=0.055) versus 3.9% (16.33) for placebo. The safety profile was consistent with the known safety profile of nipocalimab and with wAIHA-associated risks. Overall, in the double-blind ENERGY study, nipocalimab demonstrated rapid hemoglobin response and nominal improvements in fatigue that were maintained over 24 weeks, with no new safety findings in wAIHA. NCT04119050