Treatment with nipocalimab significantly improves haemoglobin (Hgb) levels as early as week 1, persisting through week 24 in patients with warm autoimmune haemolytic anaemia (wAIHA), according to the ENERGY trial presented at EHA 2026.
“These data from the phase II/III ENERGY study showed the rapid onset of effect and durable improvement in anaemia, which occurs 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 that people living with wAIHA experience.”
This double-blind, placebo-controlled trial analysed 120 adults (mean age 55 years) diagnosed with primary or secondary wAIHA who were currently or previously treated with corticosteroids (≥3 months) and/or immunosuppressants. Participants were randomized to receive either intravenous nipocalimab at two different 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, a higher percentage of patients treated with nipocalimab achieved a durable Hgb response than those treated with placebo (23.7 percent; p=0.015 [30 mg/kg Q4W] and 21.1 percent; p=0.044 [15 mg/kg Q2W] vs 7.7 percent), although the latter finding did not reach statistical significance. [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.
Additionally, in a prespecified analysis of patients with durable Hgb response, those receiving nipocalimab 30 mg/kg Q4W or 15 mg/kg Q2W achieved an Hgb level ≥10 g/dL and an increase of ≥2 g/dL at ≥1 visit vs those on placebo (60.5 percent; pnominal<0.001 and 42.1 percent; pnominal<0.01, respectively, vs 15.4 percent).
With regard to the secondary endpoints, patients treated with nipocalimab experienced an improvement in FACIT*-Fatigue total score at week 24 compared with those on placebo (mean change from baseline, 3.4 points; pnominal=0.007 [30 mg/kg Q4W] and 1.2 points; pnominal=0.267 [15 mg/kg Q2W] vs 0.6 points).
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 who were on corticosteroids at baseline, those treated with nipocalimab were more likely to reduce their average daily corticosteroid dose by week 24 than those treated with placebo (mean change from baseline –15.1 percent [30 mg/kg Q4W] and –14.1 percent [15 mg/kg Q2W] vs –3.9 percent).
In terms of safety, the rates of treatment-emergent adverse events were comparable between the nipocalimab and placebo groups (81.1 percent to 92.1 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, 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 show 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.