Treatment with nipocalimab significantly improves haemoglobin (Hgb) levels as early as week 1, with effects persisting through week 24 in patients with warm autoimmune haemolytic anaemia (wAIHA), according to the phase II/III ENERGY trial presented at EHA 2026.
“Data from this study showed rapid onset of effect and durable improvement in anaemia, achieved by targeting the autoantibody-mediated destruction of red blood cells in people living with wAIHA,” said Prof Bruno Fattizzo from Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy. “Achieving Hgb improvements this quickly and at this scale is important in clinical practice, as it could help improve the debilitating fatigue experienced by people living with wAIHA.”
This double-blind, placebo-controlled trial analysed 120 adults (mean age 55 years) with primary or secondary wAIHA who had been treated with corticosteroids (≥3 months) and/or immunosuppressants either currently or previously. Participants were randomized to receive IV nipocalimab at two dose schedules (30 mg/kg Q4W [n=38] or 15 mg/kg Q2W [n=38]) or placebo (n=39) for 24 weeks.
The primary endpoint of the study was durable Hgb response, defined as the percentage of patients achieving an Hgb increase of ≥2 g/dL from baseline and reaching Hgb ≥10 g/dL for three consecutive visits (≥28 days), without the need for rescue therapy.
At week 24, the proportion of participants who achieved a durable Hgb response was higher with nipocalimab 30 mg/kg Q4W than with placebo (23.7 percent; p=0.015). A similar pattern was observed between nipocalimab 15 mg/kg Q2W and placebo, but the comparison did not reach statistical significance (21.1 percent vs 7.7 percent; p=0.044). [EHA 2026, abstract S300]
Notably, as early as week 1, the mean Hgb increased by 1.1 g/dL in the nipocalimab 30 mg/kg Q4W group and by 0.7 g/dL in the 15 mg/kg Q2W group, whereas it decreased by 0.1 g/dL in the placebo group.
Among patients with durable Hgb response, the percentage of patients who achieved an Hgb level ≥10 g/dL and an increase of ≥2 g/dL at ≥1 visit was markedly higher with nipocalimab 30 mg/kg Q4W than with placebo (60.5 percent vs 15.4 percent; pnominal<0.001). The same was true in the comparison between nipocalimab 15 mg/kg Q2W and placebo (42.1 percent vs 15.4 percent; pnominal<0.01).
With regard to the secondary endpoints, the 24-week improvements in FACIT*-Fatigue total score were greater with nipocalimab than with placebo (mean changes from baseline, 3.4 vs 0.6 points; pnominal=0.007 [30 mg/kg Q4W] and 1.2 points vs 0.6 points; pnominal=0.267 [15 mg/kg Q2W]).
Fattizzo stated that “for nipocalimab 30 mg/kg Q4W, improvements in fatigue were evident as early as week 2 and maintained through week 24.”
Furthermore, among patients on corticosteroids at baseline, 14–15 percent of participants treated with the experimental agent experienced corticosteroid reductions by week 24, whereas with placebo, only 4 percent reduced their average daily corticosteroid dose by week 24.
In terms of safety, the rates of treatment-emergent adverse events were comparable between the nipocalimab and placebo groups (81.1–s1 percent vs 89.5 percent).
Grade ≥3 infection rates were lower with nipocalimab than with placebo (5.3 percent [30 mg/kg Q4W] and 8.1 percent [15 mg/kg Q2W] vs 12.8 percent). None of the nipocalimab-treated patients developed hypogammaglobulinemia or hypoalbuminemia, which are potential side effects of nipocalimab, said Fattizzo.
The overall safety findings were consistent with the known safety profile of nipocalimab, with no new safety signals identified.
Nipocalimab is the first FcRn** blocker to demonstrate both efficacy and safety in treating wAIHA. In particular, nipocalimab 30 mg/kg Q4W demonstrated rapid and sustained efficacy in achieving the strict primary Hgb response through week 24, Fattizzo said.