VYVGART

5 WARNINGS AND PRECAUTIONS Infections: Delay administration of VYVGART to patients with an active infection. Monitor for signs and symptoms of infection in patients treated with VYVGART. If serious infection occurs, administer appropriate treatment and consider withholding VYVGART until the infection has resolved. ( 5.1 ) Hypersensitivity Reactions: Anaphylaxis, hypotension leading to syncope, angioedema, dyspnea, and rash have occurred. If a hypersensitivity reaction occurs, the healthcare professional should institute appropriate measures if needed or the patient should seek medical attention. ( 4 , 5.2 ) Infusion-Related Reactions: If a severe infusion-related reaction occurs, discontinue the infusion and initiate appropriate therapy; consider risks and benefits of readministering. If a mild to moderate infusion-related reaction occurs, consider rechallenging with close clinical observation, slower infusion rates, and pre-medications. ( 5.3 ) 5.1 Infections VYVGART may increase the risk of infection. The most common infections observed in Study 1 were urinary tract infection (10% of VYVGART-treated patients compared to 5% of placebo-treated patients) and respiratory tract infections (33% of VYVGART-treated patients compared to 29% of placebo-treated patients) [see Adverse Reactions (6.1) and Clinical Studies (14) ] . A higher frequency of patients who received VYVGART compared to placebo were observed to have below normal levels for white blood cell counts (12% versus 5%, respectively), lymphocyte counts (28% versus 19%, respectively), and neutrophil counts (13% versus 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. During treatment with VYVGART, 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 Evaluate the need to administer age-appropriate vaccines according to immunization guidelines before initiation of a new treatment cycle with VYVGART. The safety of immunization with live vaccines and the immune response to vaccination during treatment with VYVGART are unknown. Because VYVGART causes a reduction in IgG levels, vaccination with live vaccines is not recommended during treatment with VYVGART. 5.2 Hypersensitivity Reactions In clinical trials, hypersensitivity reactions, including rash, angioedema, and dyspnea were observed in VYVGART-treated patients. Hypersensitivity reactions were mild or moderate, occurred within one hour to three weeks of administration, and did not lead to treatment discontinuation. Anaphylaxis and hypotension leading to syncope have been reported in postmarketing experience with VYVGART. Anaphylaxis and hypotension occurred during or within an hour of administration and led to infusion discontinuation and in some cases to permanent treatment discontinuation. Monitor patients during administration and for 1 hour thereafter 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. VYVGART is contraindicated in patients with a history of serious hypersensitivity to efgartigimod alfa products or to any of the excipients of VYVGART [see Contraindications (4) ] . 5.3 Infusion-Related Reactions Infusion-related reactions have been reported with VYVGART 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. Consider the risks and benefits of readministering VYVGART 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.

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Infections [see Warnings and Precautions (5.1) ] Hypersensitivity Reactions [see Warnings and Precautions (5.2) ] Infusion-Related Reactions [see Warnings and Precautions (5.3) ] Most common adverse reactions (≥ 10%) in patients treated with gMG are respiratory tract infections, headache, and urinary tract infection. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact argenx at 1-833-argx411 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In clinical studies, the safety of VYVGART in adult patients with gMG has been evaluated in 364 patients who received at least one dose of VYVGART. In a placebo-controlled study (Study 1) in patients with gMG, 84 patients received VYVGART 10 mg/kg [see Clinical Studies (14) ]. Of these 84 patients, approximately 75% were female, 82% were White, 11% were Asian, and 8% were of Hispanic or Latino ethnicity. The mean age at study entry was 46 years (range 19 to 78). The minimum time to initiate a subsequent cycle, specified by study protocol, was 28 days from the last administration of the previous treatment cycle. On average, VYVGART-treated patients received 2 cycles in Study 1. The mean and median times to the second treatment cycle were 54 days and 50 days from the last administration of the first treatment cycle, respectively, for VYVGART-treated patients. Adverse reactions reported in at least 5% of patients treated with VYVGART and more frequently than placebo are summarized in Table 1. The most common adverse reactions (reported in at least 10% of VYVGART-treated patients) were respiratory tract infection, headache, and urinary tract infection. Table 1: Adverse Reactions in ≥ 5% of Patients Treated with VYVGART and More Frequently than in Placebo-Treated Patients in Study 1 (Safety Population) Adverse reaction VYVGART (N=84) % Placebo (N=83) % Respiratory tract infection 33 29 Headache Headache includes migraine and procedural headache. 32 29 Urinary tract infection 10 5 Paraesthesia Paraesthesia includes oral hypoesthesia, hypoesthesia, and hyperesthesia. 7 5 Myalgia 6 1 In the placebo-controlled study in patients with gMG who are anti-acetylcholine receptor (AChR) antibody negative (Study 2), 119 patients received one cycle of once-weekly administrations for 4 weeks of either VYVGART 10 mg/kg (n=58) or placebo (n=61). The overall safety profile in Study 2 was consistent with the known safety profile of VYVGART in patients with gMG, except for nausea, which occurred in 7% of anti-AChR antibody negative patients who received VYVGART compared to 5% of patients who received placebo. The safety of initiating subsequent cycles between 7 and 28 days from the last administration of the previous treatment cycle was assessed in another study in 60 patients with gMG (78% AChR antibody positive and 22% anti-AChR antibody negative). Of these patients, 63% were exposed to treatment for over a year when cycles were initiated less than 4 weeks after the last administration. Safety in these patients was similar to that seen in Study 1. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of VYVGART. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Immune System Disorders: Hypersensitivity reactions including anaphylaxis and hypotension, and infusion-related reactions [see Warnings and Precautions (5.2 , 5.3) ].

<table width="75%" ID="table1"><caption>Table 1: Adverse Reactions in &#x2265; 5% of Patients Treated with VYVGART and More Frequently than in Placebo-Treated Patients in Study 1 (Safety Population)</caption><col width="55%" align="left" valign="top"/><col width="25%" align="center" valign="top"/><col width="20%" align="center" valign="top"/><thead><tr><th styleCode="Lrule Rrule" align="center">Adverse reaction</th><th styleCode="Rrule">VYVGART (N=84) %</th><th styleCode="Rrule">Placebo (N=83) %</th></tr></thead><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Respiratory tract infection</td><td styleCode="Rrule">33</td><td styleCode="Rrule">29</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Headache<footnote><content styleCode="italics">Headache includes migraine and procedural headache.</content></footnote></td><td styleCode="Rrule">32</td><td styleCode="Rrule">29</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Urinary tract infection</td><td styleCode="Rrule">10</td><td styleCode="Rrule">5</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Paraesthesia<footnote><content styleCode="italics">Paraesthesia includes oral hypoesthesia, hypoesthesia, and hyperesthesia.</content></footnote></td><td styleCode="Rrule">7</td><td styleCode="Rrule">5</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Myalgia</td><td styleCode="Rrule">6</td><td styleCode="Rrule">1</td></tr></tbody></table>