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.

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. 

CONTRAINDICATIONS

VYVGART and VYVGART HYTRULO are contraindicated in patients with serious hypersensitivity to efgartigimod alfa products or to any of the excipients of VYVGART or VYVGART HYTRULO, respectively. VYVGART HYTRULO is also contraindicated in patients with serious hypersensitivity to hyaluronidase. Reactions have included anaphylaxis and hypotension leading to syncope.

WARNINGS AND PRECAUTIONS
Infection

VYVGART and VYVGART HYTRULO may increase the risk of infection. The most common infections observed in Study 1 were urinary tract infection (10% of efgartigimod alfa-fcab-treated patients vs 5% of placebo-treated patients) and respiratory tract infection (33% of efgartigimod alfa-fcab-treated patients vs 29% of placebo-treated patients). Patients on efgartigimod alfa-fcab 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 the administration of VYVGART or VYVGART HYTRULO in patients with an active infection until the infection has resolved; monitor for clinical signs and symptoms of infections. If serious infection occurs, administer appropriate treatment and consider withholding treatment with VYVGART or VYVGART HYTRULO until the infection has resolved.

Immunization

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

Hypersensitivity Reactions

In clinical trials, hypersensitivity reactions, including rash, angioedema, and dyspnea were observed in patients treated with VYVGART or VYVGART HYTRULO. Urticaria was also observed in patients treated with VYVGART HYTRULO. Hypersensitivity reactions were mild or moderate, occurred within 1 hour to 3 weeks of administration, and did not lead to treatment discontinuation. Anaphylaxis and hypotension leading to syncope have been reported in postmarketing experience with intravenous efgartigimod alfa-fcab. Anaphylaxis and hypotension occurred during or within an hour of administration and led to infusion discontinuation and in some cases to permanent treatment discontinuation. Healthcare professionals should monitor patients during and for 1 hour after VYVGART administration, or for at least 30 minutes after VYVGART HYTRULO administration, for clinical signs and symptoms of hypersensitivity reactions. If a hypersensitivity reaction occurs, the healthcare professional should institute appropriate measures if needed or the patient should seek medical attention.

Infusion-Related Reactions

Infusion-related reactions have been reported with intravenous efgartigimod alfa-fcab in postmarketing experience. The most frequent symptoms and signs were hypertension, chills, shivering, and thoracic, abdominal, and back pain. Infusion-related reactions occurred during or within an hour of administration and led to infusion discontinuation. If a severe infusion-related reaction occurs during administration, discontinue VYVGART infusion and initiate appropriate therapy. If a severe infusion-related reaction occurs with VYVGART HYTRULO, initiate appropriate therapy. Consider the risks and benefits of readministering VYVGART or VYVGART HYTRULO following a severe infusion-related reaction. If a mild to moderate infusion-related reaction occurs, patients may be rechallenged with close clinical observation, slower infusion rates, and pre-medications.

ADVERSE REACTIONS

In Study 1, the most common (≥10%) adverse reactions in efgartigimod alfa-fcab-treated patients were respiratory tract infection, headache, and urinary tract infection. In Study 2, the most common (≥10%) adverse reactions in VYVGART HYTRULO-treated patients were injection site reactions and headache. Injection site reactions occurred in 38% of VYVGART HYTRULO-treated patients, including injection site rash, erythema, pruritus, bruising, pain, and urticaria. In Study 2 and its open-label extension, all injection site reactions were mild to moderate in severity and did not lead to treatment discontinuation. The majority occurred within 24 hours after administration and resolved spontaneously. Most injection site reactions occurred during the first treatment cycle, and the incidence decreased with each subsequent cycle.

USE IN SPECIFIC POPULATIONS
Pregnancy

As VYVGART and VYVGART HYTRULO are 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 or VYVGART HYTRULO in utero.

Lactation

There is no information regarding the presence of efgartigimod alfa-fcab from administration of VYVGART, or efgartigimod alfa or hyaluronidase from administration of VYVGART HYTRULO, 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 or VYVGART HYTRULO, and any potential adverse effects on the breastfed infant from VYVGART or VYVGART HYTRULO or from the underlying maternal condition.

INDICATION

VYVGART® (efgartigimod alfa-fcab) for intravenous infusion and VYVGART® HYTRULO (efgartigimod alfa and hyaluronidase-qvfc) for subcutaneous injection are each 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 for VYVGART and the full Prescribing Information for VYVGART HYTRULO.

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).

CONTRAINDICATIONS

VYVGART and VYVGART HYTRULO are contraindicated in patients with serious hypersensitivity to efgartigimod alfa products or to any of the excipients of VYVGART or VYVGART HYTRULO, respectively. VYVGART HYTRULO is also contraindicated in patients with serious hypersensitivity to hyaluronidase. Reactions have included anaphylaxis and hypotension leading to syncope.

WARNINGS AND PRECAUTIONS
Infection

VYVGART and VYVGART HYTRULO may increase the risk of infection. The most common infections observed in Study 1 were urinary tract infection (10% of efgartigimod alfa-fcab-treated patients vs 5% of placebo-treated patients) and respiratory tract infection (33% of efgartigimod alfa-fcab-treated patients vs 29% of placebo-treated patients). Patients on efgartigimod alfa-fcab 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 the administration of VYVGART or VYVGART HYTRULO in patients with an active infection until the infection has resolved; monitor for clinical signs and symptoms of infections. If serious infection occurs, administer appropriate treatment and consider withholding treatment with VYVGART or VYVGART HYTRULO until the infection has resolved.

Immunization

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

Hypersensitivity Reactions

In clinical trials, hypersensitivity reactions, including rash, angioedema, and dyspnea were observed in patients treated with VYVGART or VYVGART HYTRULO. Urticaria was also observed in patients treated with VYVGART HYTRULO. Hypersensitivity reactions were mild or moderate, occurred within 1 hour to 3 weeks of administration, and did not lead to treatment discontinuation. Anaphylaxis and hypotension leading to syncope have been reported in postmarketing experience with intravenous efgartigimod alfa-fcab. Anaphylaxis and hypotension occurred during or within an hour of administration and led to infusion discontinuation and in some cases to permanent treatment discontinuation. Healthcare professionals should monitor patients during and for 1 hour after VYVGART administration, or for at least 30 minutes after VYVGART HYTRULO administration, for clinical signs and symptoms of hypersensitivity reactions. If a hypersensitivity reaction occurs, the healthcare professional should institute appropriate measures if needed or the patient should seek medical attention.

Infusion-Related Reactions

Infusion-related reactions have been reported with intravenous efgartigimod alfa-fcab in postmarketing experience. The most frequent symptoms and signs were hypertension, chills, shivering, and thoracic, abdominal, and back pain. Infusion-related reactions occurred during or within an hour of administration and led to infusion discontinuation. If a severe infusion-related reaction occurs during administration, discontinue VYVGART infusion and initiate appropriate therapy. If a severe infusion-related reaction occurs with VYVGART HYTRULO, initiate appropriate therapy. Consider the risks and benefits of readministering VYVGART or VYVGART HYTRULO following a severe infusion-related reaction. If a mild to moderate infusion-related reaction occurs, patients may be rechallenged with close clinical observation, slower infusion rates, and pre-medications.

ADVERSE REACTIONS

In Study 1, the most common (≥10%) adverse reactions in efgartigimod alfa-fcab-treated patients were respiratory tract infection, headache, and urinary tract infection. In Study 2, the most common (≥10%) adverse reactions in VYVGART HYTRULO-treated patients were injection site reactions and headache. Injection site reactions occurred in 38% of VYVGART HYTRULO-treated patients, including injection site rash, erythema, pruritus, bruising, pain, and urticaria. In Study 2 and its open-label extension, all injection site reactions were mild to moderate in severity and did not lead to treatment discontinuation. The majority occurred within 24 hours after administration and resolved spontaneously. Most injection site reactions occurred during the first treatment cycle, and the incidence decreased with each subsequent cycle.

USE IN SPECIFIC POPULATIONS
Pregnancy

As VYVGART and VYVGART HYTRULO are 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 or VYVGART HYTRULO in utero.

Lactation

There is no information regarding the presence of efgartigimod alfa-fcab from administration of VYVGART, or efgartigimod alfa or hyaluronidase from administration of VYVGART HYTRULO, 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 or VYVGART HYTRULO, and any potential adverse effects on the breastfed infant from VYVGART or VYVGART HYTRULO or from the underlying maternal condition.

INDICATION

VYVGART® (efgartigimod alfa-fcab) for intravenous infusion and VYVGART® HYTRULO (efgartigimod alfa and hyaluronidase-qvfc) for subcutaneous injection are each 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 for VYVGART and the full Prescribing Information for VYVGART HYTRULO.

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