Nipocalimab-aahu Injection (Imaavy)
June 15, 2025
By William Elliott, MD, FACP, and James Chan, PharmD, PhD
The U.S. Food and Drug Administration has approved a neonatal Fc-receptor (FcRn) blocker for the treatment of generalized myasthenia gravis (gMG). Nipocalimab-aahu is a recombinant human immunoglobulin G1 lambda (IgG1-lambda) monoclonal antibody directed at FcRn with high affinity and selectivity. It is the third neonatal Fc receptor blocker approved (after efgartigimod [Vyvgrt] and rozanolixizumab [Rystiggo]) and the second approved for patients with both anti-acetylcholine receptor (AChR)- and anti-muscle-specific tyrosine kinase (MuSK)-positive antibodies (after rozanolixizumab), and the first approved for pediatric patients (≥ 12 years of age). Nipocalimab is distributed by Janssen Biotech Inc. as Imaavy.
Indications
Nipocalimab is indicated for the treatment of gMG in adult and pediatric patients 12 years of age and older who are anti-AChR- or anti-MuSK antibody-positive.1
Dosage
The recommended initial dose is 30 mg/kg once by intravenous infusion over at least 30 minutes.1 The maintenance dose (15 mg/kg) is administered over at least 15 minutes two weeks after the initial dose and is continued every two weeks thereafter. Nipocalimab is available as 300-mg/1.62-mL and 1,200-mg/6.5-mL single-dose vials.
Potential Advantages
Nipocalimab selectively reduces circulating immunoglobulin G (IgG) levels without detectable effect on other adaptive and innate immune functions and reduces anti-AChR receptor and anti-MuSK autoantibody levels.1-3
Potential Disadvantages
Nipocalimab may increase the risk of infection or activation of latent viral infections, such as herpes zoster.1 Infusion-related reactions (headache, influenza-like illness, rash, nausea, fatigue, dizziness, chills, and erythema) were observed.1 Hypersensitivity reactions (angioedema, anaphylaxis, rash, urticaria, and eczema) also have been observed. The most common adverse reactions (> 10%) are peripheral edema (12% vs. 2% for placebo) and muscle spasm (12% vs. 3%).1
Comments
Nipocalimab binds to Fc receptors, leading to increased clearance and a reduction of circulating IgG levels.1 The efficacy and safety of nipocalimab was evaluated in a randomized, double-blind, placebo-controlled, 24-week study.1,3 Inclusion criteria in the study were Myasthenia Gravis Foundation of America Clinical Classification Class II to IV, Myasthenia Gravis-Activities of Daily Living (MG-ADL) total score of at least 6, and being on a stable dose of standard of myasthenia gravis therapy prior to baseline (i.e., acetylcholinesterase inhibitors, steroid or non-steroidal immunosuppressives).
Study participants at baseline had a median MG-ADL total score of 9, a median Quantitative Myasthenia Gravis (QMG) total score of 15, 88% were AChR antibody-positive, 10% were anti-MuSK-positive, had a mean age of 52.3 years, 60% were female, and 63% were white. Participants were randomized to the nipocalimab plus standard of care (n = 100) arm or the placebo plus standard of care (n = 99) arm. The analytical dataset included 77 in the nipocalimab group and 76 in the placebo group.
The primary efficacy endpoint was the change in MG-ADL total score from baseline to weeks 22, 23, and 24. The secondary endpoint was the change of QMG total score from baseline to weeks 22 and 24. QMG assesses muscle weakness (13-item four-point scale, range 0-39). Nipocalimab produced a statistically significant mean change in MG-ADL of -4.7, compared with -3.3 for placebo. Forty-seven percent of participants in the nipocalimab group showed a ≥ 50% improvement vs. 25% for the placebo group. QMG total score also was statistically reduced (-4.9 and -2.1, respectively). IgG was reduced by 74.6% at week 2 and 68.8% at week 24.3
Clinical Implications
Myasthenia gravis is a rare chronic autoimmune disorder resulting in muscle weakness and fatigue. The disease can have periods of improvement as well as flare-ups.4 Abnormal antibodies are produced, including AChR and MuSK antibodies. Treatment options are thymectomy, acetylcholinesterase inhibitors, corticosteroids, non-steroid immunosuppressives, B-cell-directed drugs (e.g., rituximab), complement inhibitors (e.g., eculizumab, ravulizumab, zilucoplan), and neonatal Fc receptor blockers.4
Currently, there are two drugs approved for both anti-AChR an anti-MuSK antibody-positive myasthenia gravis — rozanolixizumab and, now, nipocalimab. There are no direct comparisons between these two drugs. Several systematic reviews/meta-analyses/network analyses suggest rozanolixizumab to be more effective than nipocalimab but with a higher incidence of adverse reactions.5-7 Rozanolixiumab is administered using as-needed dosing (i.e., experiencing symptom-worsening and subsequent treatment cycles are based on clinical evaluation), while nipocalimab is dosed every two weeks. Nipocalimab may provide an option for patients (particularly pediatric patients) positive for anti-AChR and anti-MUSK antibodies.
Nipocalimab also has been granted breakthrough therapy status for the treatment of moderate-to-severe Sjögren disease.8 It also is being evaluated for hemolytic disease in fetuses and newborns.9 The cost for an initial dose for an adult (70 kg) is $24,960 (two single-dose vials) and $12,480 (one single-dose vial) for each maintenance dose.
References
- Janssen Biotech, Inc. Imaavy prescribing information. Revised April 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/761430s000lbl.pdf
- Seth NP, Xu R, DuPrie M, et al. Nipocalimab, an immunoselective FcRn blocker that lowers IgG and has unique molecular properties. Mabs. 2025;17(1):2461191.
- Antozzi C, Vu T, Ramchandren S, et al. Safety and efficacy of nipocalimab in adults with generalised myasthenia gravis (Vivacity-MG3): A phase 3, randomised, double-blind, placebo-controlled study. Lancet Neurol. 2025;24(2):105-116.
- Myasthenia gravis treatments. Myasthenia Gravis Foundation of America. https://myasthenia.org/myasthenia-gravis-treatments/#Treatment-options-medicine
- Chen H, Qiu Y, Yin Z, et al. Efficacy and safety of the innovative monoclonal antibodies in adults with generalized myasthenia gravis: A Bayesian network analysis. Front Immunol. 2023:14:1280226.
- Ma Y, Nie X, Zhu G, et al. The efficacy and safety of different targeted drugs for the treatment of generalized myasthenia gravis: A systematic review and Bayesian network meta-analysis. CNS Drugs. 2024;38(2):93-104.
- Li J, Wu X, Chu T, et al. The efficacy and safety of FcRn inhibitors in patients with myasthenia gravis: A systematic review and meta-analysis. J Neurol. 2024;271(5):2298-2308.
- Gallagher A. FDA grants breakthrough therapy designation for nipocalimab to treat Sjögren disease. Published Nov. 19, 2024. Pharmacy Times. https://www.pharmacytimes.com/view/fda-grants-breakthrough-therapy-designation-for-nipocalimab-for-sj-gren-disease
- Moise KH, Ling LE, Oepkes D, et al. Nipocalimab in early-onset severe hemolytic disease of the fetus and newborn. N Engl J Med. 2024;391(6):526-537.
The U.S. Food and Drug Administration has approved a neonatal Fc-receptor (FcRn) blocker for the treatment of generalized myasthenia gravis. Nipocalimab-aahu is a recombinant human immunoglobulin G1 lambda monoclonal antibody directed at FcRn with high affinity and selectivity.
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