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(nipocalimab-aahu)

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IMAAVY™ (nipocalimab-aahu)
Medical Information

IMAAVY - Effect on Immunogenicity in Patients with Warm Autoimmune Hemolytic Anemia

Last Updated: 09/06/2026

Summary

  • The company cannot recommend any practices, procedures, or usage of IMAAVY that deviate from the approved labeling.
  • In the phase 2/3 ENERGY study, treatment-emergent antidrug antibodies (ADAs) were seen in 43.1% (31/72) of patients treated with IMAAVY.1
    • A total of 54.8% (n=17) of patients with treatment-emergent ADAs were positive for neutralizing antibodies (NAbs). Overall, 23.6% (17/72) of patients were positive for NAbs.
    • No ADA-related effects on immunoglobulin G (IgG), pharmacodynamic (PD) response, or serum nipocalimab concentrations were observed.

CLInical data

ENERGY study

  • Fattizzo et al (2026)2 evaluated the efficacy and safety of IMAAVY in adults with wAIHA (warm autoimmune hemolytic anemia) in a phase 2/3 multicenter, randomized, double-blind, placebo (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:2,3
    • Hemoglobin (Hgb) <10 g/dL
    • Signs of hemolysis (lactate dehydrogenase >upper limit of normal [ULN], or indirect bilirubin >ULN, or haptoglobin <lower limit of normal)
    • Direct antiglobulin test positive for IgG only or IgG and 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 phase, and safety follow-up at 8 weeks after the last infusion.2
  • Eligible patients were randomized (1:1:1) to receive intravenous (IV) IMAAVY 30 mg/kg every 4 weeks (Q4W), IMAAVY 15 mg/kg every 2 weeks (Q2W), or matching PBO Q2W through week 24.2
  • Immunogenicity was assessed as an exploratory objective and included evaluation of the occurrence of total ADAs and NAbs following treatment with IMAAVY.1
  • Serum samples were analyzed for ADA to IMAAVY using a validated, highly sensitive, drug-tolerant electrochemiluminescence immunoassay (ECLIA).1
  • Samples that tested positive for ADA to IMAAVY were subsequently evaluated for NAbs using a non-cell-based competitive ligand-binding ECLIA assay.1
  • The immunogenicity analysis population included all patients who received at least 1 full dose of IMAAVY and had appropriate samples for detection of antibodies to IMAAVY. This included 3 patients who received IMAAVY 30 mg/kg Q2W; however, this regimen was subsequently discontinued.1

Results

Immunogenicity Assessments: ADAs and NAbs

  • Among 72 patients treated with IMAAVY who had appropriate samples during the double-blind treatment period, 31 patients (43.1%) developed treatment-emergent ADAs.1 The incidence of treatment-emergent ADAs was 46.9% (15/32) in the 30 mg/kg Q4W group and 40.5% (15/37) in the IMAAVY 15 mg/kg Q2W group (see Table: Immunogenicity Outcomes During the Double-Blind Period).1
  • Most patients who were ADA-positive had low antibody titers. All patients had titer levels <1:1,000 except for 4 patients in the 30 mg/kg Q4W group, of which one had a peak titer of 1:2,560.1
  • Among the 31 patients with treatment-emergent ADAs, 17 patients (54.8%) were positive for NAbs.1
  • Overall, treatment-emergent NAbs were detected in 23.6% (17/72) of patients.1

Immunogenicity Outcomes During the Double-Blind Period1
Parameter
IMAAVY
30 mg/kg
Q4W
15 mg/kg
Q2W
Analysis set: Immunogenicity, n
33
37
Patients with appropriate samplesa, n
32
37
ADA, n (%)
   Baseline ADA-positiveb
4 (12.5)
2 (5.6)
   Treatment-boosted baseline ADAc
3 (75.0)
0
   Non treatment-boosted baseline ADAd
1 (25.0)
2 (100.0)
   Treatment-induced ADA positivee
12 (37.5)
15 (40.5)
   Treatment-emergent ADA-positivef
15 (46.9)
15 (40.5)
   Treatment-emergent ADA-negativeg
17 (53.1)
22 (59.5)
NAb
   Treatment-emergent ADA-positiveh, n
15
15
   Evaluable for NAbsi, n
15
15
   NAb-positive, n (%)j
9 (60.0)
7 (46.7)
   NAb-negativek, n (%)
6 (40.0)
8 (53.3)
   Overall NAb-positive incidencel, n (%)
9 (28.1)
7 (18.9)
   Overall NAb-negative incidencel, n (%)
6 (18.8)
8 (21.6)
Abbreviations: ADA, antidrug antibody; NAb, neutralizing antibody; Q2W, every 2 weeks; Q4W, every 4 weeks.
aPatients with appropriate samples had ≥1 sample obtained after first IMAAVY administration through week 24.
bPatients positive for ADA to IMAAVY at baseline, regardless of status after first IMAAVY administration through week 24.
cPatients with treatment-boosted ADA to IMAAVY had an antibody-positive sample before IMAAVY administration and at least one antibody-positive sample after IMAAVY administration with a 4-fold increase in titer over baseline through week 24. Patients with baseline-positive samples without a 4-fold increase in titer after treatment were not considered treatment-boosted through week 24.
dIncludes patients positive for ADA to IMAAVY at baseline whose titers did not increase 4-fold after first treatment intervention through week 24.
eIncludes patients with an antibody-negative sample before IMAAVY administration and at least one antibody-positive sample after IMAAVY administration at any time through week 24.
fPatients positive for treatment-emergent ADA to IMAAVY included all patients who were treatment-boosted or treatment-induced at any time after first IMAAVY administration through week 24.
gExcludes patients who were treatment-emergent positive at any time through week 24.
hPatients positive for treatment-emergent ADA to IMAAVY includes all patients who were positive (treatment-boosted or treatment-induced) at any time after their first IMAAVY administration through week 24.
iAn evaluable patient is a patient positive for treatment-emergent ADA to IMAAVY who was evaluated for NAbs.
jPatients positive for NAbs from treatment-emergent ADA to IMAAVY positive patients. The denominator is the number of patients evaluable for NAbs.
kExcludes patients positive for NAbs at any time. The denominator is the number of patients evaluable for NAbs.
lThe denominator is the number of patients with appropriate samples.

Impact of ADAs and NAbs on Efficacy

  • No apparent trend suggesting an effect of ADAs on efficacy outcomes was observed. Similarly, no trend between NAb positivity and efficacy was identified.1
  • Interpretation of these findings was limited by the small number of ADA- and NAb-positive patients.1

Impact of ADAs and NAbs on PD and Pharmacokinectics

  • No trend indicating an effect of ADAs on IgG was observed.1
  • Likewise, NAb positivity did not appear to affect the PD response to IMAAVY, although conclusions were limited by the small patient numbers.1
  • Postdose serum nipocalimab concentrations were generally comparable between ADA- positive and ADA-negative patients.1

LITERATURE SEARCH

A literature search of MEDLINE®, EMBASE®, BIOSIS Previews®, and DERWENT® (and/or other resources, including internal/external databases) was conducted on 31 August 2026.

References

Show
1 Data on File. Interim Clinical Study Report v1.0. Janssen Research & Development, LLC. EDMS-RIM-1468941; 2026.  
2 Fattizzo B, Murakhovskaya I, Ueda Y, et al. Nipocalimab for warm autoimmune hemolytic anemia: results from the phase 2/3 randomized, double-blind ENERGY study. [published online ahead of print August 28, 2026]. Blood. doi:10.1182/blood.2026034036.  
3 Fattizzo B, Murakhovskaya I, Ueda Y, et al. Supplement to: Nipocalimab for warm autoimmune hemolytic anemia: results from the phase 2/3 randomized, double-blind ENERGY study. [published online ahead of print August 28, 2026]. Blood. doi:10.1182/blood.2026034036.  

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