MECHANISM OF ACTION

VYVGART competes with IgG antibodies, including pathogenic AChR autoantibodies, in binding to and blocking FcRn1,2

AChR=acetylcholine receptor; FcRn=neonatal Fc receptor; IgG=immunoglobulin G.

Discover more about how VYVGART binds to and blocks FcRn––a unique approach in the treatment of anti-AChR antibody positive gMG1,3

AChR=acetylcholine receptor; FcRn=neonatal Fc receptor; gMG=generalized myasthenia gravis.

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AChR autoantibodies exert a direct pathogenic effect in gMG4-8

AChR autoantibodies disrupt neurotransmission in 3 ways:

1. Binding to AChR and creating a functional blockade

2. Cross-linking of AChR, leading to internalization and degradation

3. Activating the autoantibody dependent complement system

AChR=acetylcholine receptor; C1=complement component 1; gMG=generalized myasthenia gravis; NMJ=neuromuscular junction. 

FcRn plays a key role in gMG by perpetuating IgG antibodies4-9

FcRn binds IgG antibodies, preventing them from being destroyed in the lysosome. In doing so, FcRn helps maintain high levels of circulating IgG antibodies, including AChR autoantibodies.

Through this process, FcRn perpetuates the ability of AChR autoantibodies to attack structures such as AChR and damage the NMJ.

AChR=acetylcholine receptor; FcRn=neonatal Fc receptor; gMG=generalized myasthenia gravis; IgG=immunoglobulin G; NMJ=neuromuscular junction.

Elements of mechanism of action

VYVGART

IgG

AChR autoantibody

FcRn

VYVGART targets FcRn, a unique approach in the treatment of anti-AChR antibody positive gMG1,3

AChR=acetylcholine receptor; FcRn=neonatal Fc receptor; gMG=generalized myasthenia gravis; IgG=immunoglobulin G; NMJ=neuromuscular junction. 

Infection

VYVGART may increase the risk of infection. The most common infections observed in Study 1 were urinary tract infection (10% for VYVGART vs 5% for placebo) and respiratory tract infection (33% for VYVGART vs 29% for placebo). Patients on VYVGART vs placebo had below normal levels for white blood cell counts (12% vs 5%, respectively), lymphocyte counts (28% vs 19%, respectively), and neutrophil counts (13% vs 6%, respectively). The majority of infections and hematologic abnormalities were mild to moderate in severity. Delay VYVGART administration in patients with an active infection until the infection is resolved; monitor for clinical signs and symptoms of infections. If serious infection occurs, administer appropriate treatment and consider withholding VYVGART until the infection has resolved.

Immunization

Immunization with vaccines during VYVGART treatment has not been studied; the safety with live or live-attenuated vaccines and the response to immunization with any vaccine are unknown. Because VYVGART causes a reduction in immunoglobulin G (IgG) levels, vaccination with live-attenuated or live vaccines is not recommended during VYVGART treatment. Evaluate the need to administer age-appropriate vaccines according to immunization guidelines before initiation of a new treatment cycle with VYVGART.

Hypersensitivity Reactions

Hypersensitivity reactions, including rash, angioedema, and dyspnea, were observed with VYVGART. In clinical trials, hypersensitivity reactions were mild or moderate, occurred within 1 hour to 3 weeks of administration, and did not lead to treatment discontinuation. Monitor patients during administration and for 1 hour thereafter for clinical signs and symptoms of hypersensitivity reactions. If a hypersensitivity reaction occurs during administration, discontinue VYVGART infusion and institute appropriate supportive measures if needed.

ADVERSE REACTIONS

The most common (≥10%) adverse reactions with VYVGART were respiratory tract infection, headache, and urinary tract infection.

USE IN SPECIFIC POPULATIONS

Pregnancy

As VYVGART is expected to reduce maternal IgG antibody levels, reduction in passive protection to the newborn is anticipated. Risks and benefits should be considered prior to administering live or live-attenuated vaccines to infants exposed to VYVGART in utero.

Lactation

There is no information regarding the presence of VYVGART in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for VYVGART and any potential adverse effects on the breastfed infant from VYVGART or from the underlying maternal condition.

INDICATION

VYVGART® (efgartigimod alfa-fcab) is indicated for the treatment of generalized myasthenia gravis in adult patients who are anti-acetylcholine receptor (AChR) antibody positive.

Please see the full Prescribing Information.

You may report side effects to the US Food and Drug Administration by visiting http://www.fda.gov/medwatch or calling 1-800-FDA-1088. You may also report side effects to argenx US, Inc, at 1-833-argx411 (1-833-274-9411).

Infection

VYVGART may increase the risk of infection. The most common infections observed in Study 1 were urinary tract infection (10% for VYVGART vs 5% for placebo) and respiratory tract infection (33% for VYVGART vs 29% for placebo). Patients on VYVGART vs placebo had below normal levels for white blood cell counts (12% vs 5%, respectively), lymphocyte counts (28% vs 19%, respectively), and neutrophil counts (13% vs 6%, respectively). The majority of infections and hematologic abnormalities were mild to moderate in severity. Delay VYVGART administration in patients with an active infection until the infection is resolved; monitor for clinical signs and symptoms of infections. If serious infection occurs, administer appropriate treatment and consider withholding VYVGART until the infection has resolved.

Immunization

Immunization with vaccines during VYVGART treatment has not been studied; the safety with live or live-attenuated vaccines and the response to immunization with any vaccine are unknown. Because VYVGART causes a reduction in immunoglobulin G (IgG) levels, vaccination with live-attenuated or live vaccines is not recommended during VYVGART treatment. Evaluate the need to administer age-appropriate vaccines according to immunization guidelines before initiation of a new treatment cycle with VYVGART.

Hypersensitivity Reactions

Hypersensitivity reactions, including rash, angioedema, and dyspnea, were observed with VYVGART. In clinical trials, hypersensitivity reactions were mild or moderate, occurred within 1 hour to 3 weeks of administration, and did not lead to treatment discontinuation. Monitor patients during administration and for 1 hour thereafter for clinical signs and symptoms of hypersensitivity reactions. If a hypersensitivity reaction occurs during administration, discontinue VYVGART infusion and institute appropriate supportive measures if needed.

ADVERSE REACTIONS

The most common (≥10%) adverse reactions with VYVGART were respiratory tract infection, headache, and urinary tract infection.

USE IN SPECIFIC POPULATIONS

Pregnancy

As VYVGART is expected to reduce maternal IgG antibody levels, reduction in passive protection to the newborn is anticipated. Risks and benefits should be considered prior to administering live or live-attenuated vaccines to infants exposed to VYVGART in utero.

Lactation

There is no information regarding the presence of VYVGART in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for VYVGART and any potential adverse effects on the breastfed infant from VYVGART or from the underlying maternal condition.

INDICATION

VYVGART® (efgartigimod alfa-fcab) is indicated for the treatment of generalized myasthenia gravis in adult patients who are anti-acetylcholine receptor (AChR) antibody positive.

Please see the full Prescribing Information.

You may report side effects to the US Food and Drug Administration by visiting http://www.fda.gov/medwatch or calling 1-800-FDA-1088. You may also report side effects to argenx US, Inc, at 1-833-argx411 (1-833-274-9411).

References: 1. VYVGART. Prescribing information. argenx US Inc; 2022. 2. Howard JF Jr et al. Lancet Neurol. 2021;20(7):526-536. doi:10.1016/S1474-4422(21)00159-9 3. Wolfe GI et al. J Neurol Sci. 2021;430:118074. doi:10.1016/j.jns.2021.118074 4. Roopenian DC, Akilesh S. Nat Rev Immunol. 2007;7(9):715-725. doi:10.1038/nri2155 5. Ward ES, Ober RJ. Trends Pharmacol Sci. 2018;39(10):892-904. doi:10.1016/j.tips.2018.07.007 6. Gilhus NE et al. Nat Rev Neurol. 2016;12(5):259-268. doi:10.1038/nrneurol.2016.44 7. Huijbers MG et al. J Intern Med. 2014;275(1):12-26. doi:10.1111/joim.12163 8. Mantegazza R et al. Neuropsychiatr Dis Treat. 2011;7:151-160. doi:10.2147/NDT.S8915 9. Ulrichts P et al. J Clin Invest. 2018;128(10):4372-4386. doi:10.1172/JCI97911 10. Koneczny I, Herbst R. Cells. 2019;8(7):671. doi:10.3390/cells8070671 11. Howard JF Jr et al. Neurology. 2019;92(23):e2661-e2673. doi:10.1212/WNL.0000000000007600