Written by Priya Bhaware (M.Pharm. Pharmacology)
The Food and Drug Administration approved Imaavy (Nipocalimab-aahu) for the treatment of generalized myasthenia gravis (gMG) in adult and paediatric patients 12 years of age and older who are anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody positive. Imaavy is a monoclonal antibody that functions as a neonatal Fc receptor (FcRn) blocker. Imaavy is developed by Johnson & Johnson and is the first treatment of its kind. It offers a new option for both adolescent and adult patients living with generalized myasthenia gravis, aiming to reduce symptoms and improve daily life.
Background and Need for New Treatments
Generalized Myasthenia Gravis (gMG) is a rare and chronic autoimmune disorder that leads to muscle weakness, making simple daily activities such as lifting your arms, chewing, swallowing, or even breathing feel extremely strenuous. The condition occurs when the immune system mistakenly attacks the neuromuscular junction and disrupts the communication pathway between nerves and muscles. This immune response, often involving harmful antibodies that target proteins like AChR or MuSK, interferes with the brain’s ability to send signals to the muscles, resulting in reduced muscle function.
Current treatments of myasthenia gravis include acetylcholinesterase inhibitors, corticosteroids, immunosuppressive drugs, plasmapheresis, plasma exchange, and intravenous immunoglobulin (IVIG). While conventional treatments can control symptoms and improve quality of life, they often come with significant side effects, invasive procedures, delayed action, flare-ups, or only temporary relief. Thus, there is a real need for more targeted and gentler treatment options, and this need and limitation have led to the development of newer, targeted therapies like monoclonal antibodies (e.g., eculizumab, ravulizumab) that aim for more precise immune modulation with fewer systemic effects, and Imaavy (nipocalimab) is the latest addition to this list of monoclonal antibodies.
Imaavy (nipocalimab-aahu): A Novel Approach
Imaavy is a targeted therapy developed to reduce specific pathogenic IgG antibodies associated with myasthenia gravis without suppressing the entire immune system. For patients who have not achieved adequate symptom control with conventional therapies, Imaavy provides a more precise mechanism of action that may improve symptom management and enhance daily functioning and quality of life.
The treatment was initially discovered by Momenta Pharmaceuticals, Inc., and subsequently licensed to Janssen Biotech, NC., a subsidiary of Johnson & Johnson, for further development and commercialization.
Imaavy exerts its therapeutic effect by binding with high affinity to the neonatal Fc receptor (FcRn) under both acidic and neutral pH conditions. This interaction prevents the recycling of IgG antibodies including the autoantibodies implicated in myeasthenia gravis leading to their accelerated degradation and substantial reduction in total circulating IgG levels.
Clinical Trials and Approval
The U.S. Food and Drug Administration (FDA) approved Imaavy based on robust efficacy and safety data from the Phase 3 Vivacity-MG3 trial (NCT04951622), supported by findings from the ongoing Vibrance-MG pediatric study (NCT05265273).
In the Vivacity-MG3 trial, 199 adults with generalized myasthenia gravis (gMG), including both antibody-positive and antibody-negative patients inadequately controlled by existing standard therapies, were randomized to receive either nipocalimab (30 mg/kg IV loading dose followed by 15 mg/kg every two weeks) in combination with standard of care or placebo plus standard of care.
Nipocalimab demonstrated clinically meaningful benefits, including a statistically significant improvement in Myasthenia Gravis–Activities of Daily Living (MG-ADL) scores. Over the 24-week treatment period, patients receiving nipocalimab experienced an average -4.70 point improvement in MG-ADL scores, compared to -3.35 points in the placebo group.
The clinical trial (NCT05265273), known as the Vibrance-MG study, is an ongoing Phase 2/3 open-label trial evaluating the safety, pharmacokinetics, and efficacy of nipocalimab in pediatric patients aged 2 to less than 18 years with generalized myasthenia gravis (gMG). The study aims to assess the effect of nipocalimab on total serum immunoglobulin G (IgG) levels, safety and tolerability, and pharmacokinetics in this population. Participants receive intravenous infusions of nipocalimab every two weeks during a 24-week active treatment phase, followed by a long-term extension phase and an 8-week safety follow-up. The primary outcome measures include changes in total serum IgG levels, while secondary endpoints assess improvements in Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores.
The result of these two trials underscore Imaavy’s potential as a targeted and effective treatment option for adults and adolescents (ongoing) living with generalized myasthenia gravis
Safety Profile
Most reported adverse events (AEs) were mild to moderate in severity. The most commonly reported adverse reactions (occurring in ≥10% of patients) in individuals with generalized myasthenia gravis treated with Imaavy were respiratory tract infections, peripheral edema, and muscle spasms. Serious side effects and treatment discontinuations were less common in the group receiving nivolumab than in those receiving placebo.
Patients receiving Imaavy should be monitored for infections, and administration should be delayed in those with active infections. If a serious infection develops during treatment, appropriate therapy should be initiated, and Imaavy should be withheld until the infection resolves.
Hypersensitivity reactions such as angioedema, anaphylaxis, rash, urticaria, and eczema have been reported with Imaavy. If such a reaction occurs, the infusion should be discontinued immediately, and appropriate medical management should be provided.
In the event of a severe infusion-related reaction, treatment with Imaavy should be stopped, and appropriate intervention should be initiated. Re-administration should only be considered after carefully weighing the risks and benefits. If a mild to moderate infusion-related reaction occurs, rechallenging may be considered with close monitoring, slower infusion rates, and premedication to minimize recurrence.
Conclusion
The approval of imaavy represents a significant advancement in addressing the complex challenges of autoimmune diseases such as generalized myasthenia gravis. By specifically targeting and reducing pathogenic IgG antibodies that interfere with nerve-to-muscle communication, Imaavy provides a novel and focused treatment option for patients whose symptoms are not adequately managed by current therapies.
In essence, imaavy targeted mechanism of action offers new hope for individuals living with gMG, particularly those who have not responded well to conventional treatments. Furthermore, its potential applicability to a broader range of autoimmune conditions underscores its versatility and the meaningful impact it may have within the field of immunology.
References
IMAAVY™ (nipocalimab-aahu) approved by FDA for treatment of Myasthenia Gravis (gMG) in ) in people aged 12 and older who test positive for AChR or MuSK antibodies, April 30, 2025, available from https://www.prnewswire.com/news-releases/johnson–johnson-receives-fda-approval-for-imaavy-nipocalimab-aahu-a-new-fcrn-blocker-offering-long-lasting-disease-control-in-the-broadest-population-of-people-living-with-generalized-myasthenia-gravis-gmg-302442650.html
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IMAAVY™ (nipocalimab-aahu),Highlights of Prescribing Information, available from https://www.drugs.com/imaavy.html
Nipocalimab pivotal Phase 3 trial demonstrates longest sustained disease control in FcRn class. Johnson & Johnson. June 28, 2024. https://www.jnj.com/media-center/press-releases/nipocalimab-pivotal-phase-3-trial-demonstrates-longest-sustained-disease-control-in-fcrn-class
Nipocalimab demonstrates sustained disease control in adolescents living with generalized myasthenia gravis in Phase 2/3 study. Johnson & Johnson. October 15, 2024. https://www.jnj.com/media-center/press-releases/nipocalimab-demonstrates-sustained-disease-control-in-adolescents-living-with-generalized-myasthenia-gravis-in-phase-2-3-study
Highlights of Prescribing Information, Imaavy (nipocalimab-aahu) injection, https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/761430s000lbl.pdf
Antozzi C, Vu T, Ramchandren S, et al, Vivacity-MG3 Study Group. 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 Feb;24(2):105-116. Doi: 10.1016/S1474-4422(24)00498-8. PMID: 39862879.
A Study of Nipocalimab in Children Aged 2 to Less Than 18 Years With Generalized Myasthenia Gravis, All clinical trials, NCT05265273, https://www.allclinicaltrials.com/study/NCT05265273
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