Selective immunosuppressants

Vyvgart

Approved 17 Dec 2021InjectionInjectable

Indications

VYVGART is indicated for the treatment of adult patients with generalized myasthenia gravis (gMG). VYVGART is a neonatal Fc receptor blocker indicated for the treatment of adult patients with generalized myasthenia gravis (gMG). ( 1 )

Contraindications

VYVGART is contraindicated in patients with serious hypersensitivity to efgartigimod alfa products or to any of the excipients of VYVGART . Reactions have included anaphylaxis and hypotension leading to syncope [see Warnings and Precautions (5.2) ] . VYVGART is contraindicated in patients with serious hypersensitivity to efgartigimod alfa products or to any of the excipients of VYVGART. ( 4 )

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 )

5.1Infections

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.

At a glance

Brand name: Vyvgart
Active substance: efgartigimod alfa
Drug class: Selective immunosuppressants, Neonatal fragment crystallizable receptor (FcRn) inhibitors
Route: Injection
Dosage form: Injectable
Applicant: Argenx BV
Status: Prescription
FDA approval: 17 Dec 2021
Application: BLA761195-001
RxCUI: 2587725

Contraindications

Warnings and precautions

5.1Infections

Pregnancy and breastfeeding

8.1Pregnancy Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to VYVGART during pregnancy. Healthcare providers and patients may call 1-855-272-6524 or go to https://www.Vyvgartpregnancy.com to enroll in or to obtain information about the registry. Risk Summary There are no available data on the use of VYVGART during pregnancy. There is no evidence of adverse developmental outcomes following the administration of VYVGART at up to 100 mg/kg/day in rats and rabbits (see Data ).

The background rate of major birth defects and miscarriage in the indicated population is unknown. In the U.S. general population, the estimated background rate of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Monoclonal antibodies are increasingly transported across the placenta as pregnancy progresses, with the largest amount transferred during the third trimester.

Therefore, efgartigimod alfa-fcab may be transmitted from the mother to the developing fetus. As VYVGART is expected to reduce maternal IgG antibody levels, reduction in passive protection to the newborn is anticipated. Risk and benefits should be considered prior to administering live vaccines to infants exposed to VYVGART in utero [see Warnings and Precautions (5.1) ]. Data Animal Data Intravenous administration of efgartigimod alfa-fcab (0, 30, or 100 mg/kg/day) to pregnant rats and rabbits throughout organogenesis resulted in no adverse effects on embryofetal development in either species.

The doses tested are 3 and 10 times the recommended human dose (RHD) of 10 mg/kg, on a body weight (mg/kg) basis. Intravenous administration of efgartigimod alfa-fcab (0, 30, or 100 mg/kg/day) to rats throughout gestation and lactation resulted in no adverse effects on pre- or postnatal development. The doses tested are 3 and 10 times the recommended human dose (RHD) of 10 mg/kg, on a body weight (mg/kg) basis.

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.

6.1Clinical 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.

6.2Postmarketing 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) ].

Vyvgart

Indications

Contraindications

Warnings and precautions

5.1Infections

At a glance

Two medicines in one question?

Vyvgart

Indications

Contraindications

Warnings and precautions

5.1Infections

At a glance

Two medicines in one question?

5.2Hypersensitivity Reactions

5.3Infusion-Related Reactions

Interactions

7.1Effect of

Pregnancy and breastfeeding

8.1Pregnancy Pregnancy Exposure Registry

Adverse reactions

6.1Clinical Trials Experience

6.2Postmarketing Experience

Composition

Official product information