VYVGART (EFGARTIGIMOD ALFA) injection

Evaluate the need to administer age-appropriate vaccines according to immunization guidelines before initiation of a new treatment cycle with VYVGART. Because VYVGART causes transient reduction in IgG levels, vaccination with live vaccines is not recommended during treatment with VYVGART [see Dosage and Administration (2.2) and Warnings and Precautions (5.1)].

Dilute VYVGART prior to administration. Administer via intravenous infusion only [see Dosage and Administration (2.3)].

The recommended dosage of VYVGART is 10 mg/kg administered as an intravenous infusion over one hour once weekly for 4 weeks. In patients weighing 120 kg or more, the recommended dose of VYVGART is 1,200 mg (3 vials) per infusion.

Administer subsequent treatment cycles based on clinical evaluation.

If a scheduled infusion is missed, VYVGART may be administered up to 3 days after the scheduled time point. Thereafter, resume the original dosing schedule until the treatment cycle is completed.

Prior to administration, dilute VYVGART single-dose vials in 0.9% Sodium Chloride Injection to make a total volume to be administered of 125 mL (see Preparation).

Check that the VYVGART solution is clear to slightly opalescent and colorless to slightly yellow. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if opaque particles, discoloration, or other foreign particles are present.

Use aseptic technique when preparing the VYVGART diluted solution for intravenous infusion. Each vial is for single-dose only.

Discard any unused portion.

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.

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)].

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.

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.

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.

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)].

Concomitant use of VYVGART with medications that bind to the human neonatal Fc receptor (FcRn) (e.g., immunoglobulin products, monoclonal antibodies, or antibody derivates containing the human Fc domain of the IgG subclass) may lower systemic exposures and reduce effectiveness of such medications. Closely monitor for reduced effectiveness of medications that bind to the human neonatal Fc receptor. When concomitant long-term use of such medications is essential for patient care, consider discontinuing VYVGART and using alternative therapies.

Safety and effectiveness in pediatric patients have not been established.

Clinical studies of VYVGART did not include sufficient numbers of patients aged 65 and older to determine whether they respond differently from younger adult patients.

No dose adjustment of VYVGART is needed for patients with mild renal impairment. There are insufficient data to evaluate the impact of moderate renal impairment (eGFR 30-59 mL/min/1.73 m²) and severe renal impairment (eGFR <30 mL/min/1.73 m²) on pharmacokinetic parameters of efgartigimod alfa-fcab [see Clinical Pharmacology (12.3)].

Efgartigimod alfa-fcab is a human IgG1 antibody fragment that binds to the neonatal Fc receptor (FcRn), resulting in the reduction of circulating IgG.

In Study 1 [see Clinical Studies (14)], the pharmacological effect of efgartigimod alfa-fcab was assessed by measuring the decrease in serum IgG levels and anti-AChR autoantibody levels. In patients testing positive for anti-AChR antibodies and who were treated with VYVGART, there was a reduction in total IgG levels relative to baseline. Decrease in anti-AChR autoantibody levels followed a similar pattern.

In Study 2 [see Clinical Studies (14)], the pharmacological effect of efgartigimod alfa-fcab was assessed by measuring the decrease in serum IgG levels and anti-muscle-specific tyrosine kinase (MuSK) autoantibody levels. In patients testing negative for anti-AChR antibodies who were treated with VYVGART, there was a reduction in total IgG levels relative to baseline. In patients testing positive for anti-MuSK antibodies, decreases in anti-MuSK autoantibodies levels followed a similar pattern as total IgG levels.

Efgartigimod alfa-fcab exhibits linear pharmacokinetics, and following single doses of efgartigimod alfa-fcab, exposures increase proportionally up to 50 mg/kg (5 times the recommended dosage).

The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of VYVGART or of other efgartigimod products.

In up to 26 weeks of treatment in Study 1, 20% (17/83) of patients developed antibodies to VYVGART. Seven percent (6/83) of patients developed neutralizing antibodies.

In part A of Study 2, in up to 8 weeks following the initiation of a treatment period with 4 weekly administrations, 18% (10/57) of patients developed antibodies to VYVGART. None of the patients developed neutralizing antibodies.

The available data are too limited to make definitive conclusions regarding immunogenicity and the effect on pharmacokinetics, safety, or efficacy of VYVGART.

Store VYVGART vials refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light until time of use. Do not freeze. Do not shake.

Refer to Dosage and Administration (2.3) for information on stability and storage of the diluted solutions of VYVGART.

Infections

Instruct patients to communicate any history of infections to the healthcare provider and to contact their healthcare provider if they develop any symptoms of an infection. Advise patients to complete age-appropriate vaccines according to immunization guidelines prior to initiation of a new treatment cycle with VYVGART. Administration of live vaccines is not recommended during treatment with VYVGART [see Warnings and Precautions (5.1)].

Hypersensitivity Reactions

Inform patients that hypersensitivity reactions, including angioedema and anaphylaxis, have occurred in patients who were treated with VYVGART. Inform patients about the signs and symptoms of these reactions, and advise patients to contact their healthcare provider immediately if these occur [see Warnings and Precautions (5.2)].

Infusion-Related Reactions

Advise patients of the potential risk of infusion-related reactions, which can include hypertension, chills, shivering, and chest, abdominal, and back pain [see Warnings and Precautions (5.3)].

Pregnancy Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to VYVGART during pregnancy. Encourage participation and advise patients about how they may enroll in the registry [see Use in Specific Populations (8.1)].