Highlights

Indications

Efgartigimod alfa and hyaluronidase-qvfc is indicated for the treatment of adult patients with:

Dosage and administration

Recommended vaccination

Evaluate the need to administer age-appropriate vaccines according to immunization guidelines before initiation of a new treatment cycle with efgartigimod alfa and hyaluronidase-qvfc. Because efgartigimod alfa and hyaluronidase-qvfc causes a transient reduction in IgG levels, vaccination with live vaccines is not recommended during treatment with efgartigimod alfa and hyaluronidase-qvfc.

Important dosage and administration instructions

Efgartigimod alfa and hyaluronidase-qvfc is for subcutaneous use only. Do not administer intravenously. Do not dilute efgartigimod alfa and hyaluronidase-qvfc.

Single-dose prefilled syringe. Efgartigimod alfa and hyaluronidase-qvfc prefilled syringe may be administered by patients and/or caregivers after proper instruction in subcutaneous injection technique.

Single-dose vial. Efgartigimod alfa and hyaluronidase-qvfc vial is to be administered with a winged infusion set by a healthcare professional only.

Recommended dosage for generalized myasthenia gravis

Single-dose prefilled syringe. The recommended dosage of efgartigimod alfa and hyaluronidase-qvfc prefilled syringe is 1,000 mg/10,000 units (1,000 mg efgartigimod alfa and 10,000 units hyaluronidase) administered subcutaneously over approximately 20 to 30 seconds in cycles of once weekly injections for 4 weeks.

Single-dose vial. The recommended dosage of efgartigimod alfa and hyaluronidase-qvfc vial is 1,008 mg/11,200 units (1,008 mg efgartigimod alfa and 11,200 units hyaluronidase) administered subcutaneously over approximately 30 to 90 seconds in cycles of once weekly injections for 4 weeks.

General dosage considerations. Administer subsequent treatment cycles according to clinical evaluation. The safety of initiating subsequent cycles sooner than 50 days from the start of the previous treatment cycle has not been established.

If a scheduled dose is missed, efgartigimod alfa and hyaluronidase-qvfc may be administered up to 3 days after the scheduled time point. Thereafter, resume the original dosing schedule until the treatment cycle is completed.

Recommended dosage for chronic inflammatory demyelinating polyneuropathy

Single-dose prefilled syringe. The recommended dosage of efgartigimod alfa and hyaluronidase-qvfc prefilled syringe is 1,000 mg/10,000 units (1,000 mg efgartigimod alfa and 10,000 units hyaluronidase) administered subcutaneously over approximately 20 to 30 seconds as once weekly injections.

Single-dose vial. The recommended dosage of efgartigimod alfa and hyaluronidase-qvfc vial is 1,008 mg/11,200 units (1,008 mg efgartigimod alfa and 11,200 units hyaluronidase) administered subcutaneously over approximately 30 to 90 seconds as once weekly injections.

General dosage considerations. If a scheduled injection is missed, efgartigimod alfa and hyaluronidase-qvfc may be administered up to 3 days after the scheduled time point. Thereafter, resume the original dosing schedule.

Preparation and administration instructions

Single-dose prefilled syringe. Take the efgartigimod alfa and hyaluronidase-qvfc prefilled syringe out of the refrigerator at least 30 minutes before injecting to allow it to reach room temperature. Do not use external heat sources to bring the syringe to room temperature.

For detailed instructions on the preparation and administration of efgartigimod alfa and hyaluronidase-qvfc prefilled syringes, see instructions for use.

Single-dose vial. Use aseptic technique when preparing and administering efgartigimod alfa and hyaluronidase-qvfc vial. Do not shake the vial. Each vial is for one-time use only. Avoid exposure to direct sunlight.

Dosage forms and strengths

Injection: 1,000 mg efgartigimod alfa and 10,000 units hyaluronidase per 5 mL (200 mg/2,000 units per mL) as a yellowish, clear to opalescent solution in a single-dose prefilled syringe.

Injection: 1,008 mg efgartigimod alfa and 11,200 units hyaluronidase per 5.6 mL (180 mg/2,000 units per mL) as a yellowish, clear to opalescent solution in a single-dose vial.

Contraindications

Efgartigimod alfa and hyaluronidase-qvfc is contraindicated in patients with serious hypersensitivity to efgartigimod alfa products, to hyaluronidase, or to any of the excipients of efgartigimod alfa and hyaluronidase-qvfc. Reactions have included anaphylaxis and hypotension leading to syncope.

Warnings and precautions

Infections

Efgartigimod alfa and hyaluronidase-qvfc 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 compared to 5% of placebo-treated patients) and respiratory tract infections (33% of efgartigimod alfa-fcab-treated patients compared to 29% of placebo-treated patients). A higher frequency of patients who received efgartigimod alfa-fcab 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 efgartigimod alfa and hyaluronidase-qvfc administration in patients with an active infection until the infection is resolved. During treatment with efgartigimod alfa and hyaluronidase-qvfc, monitor for clinical signs and symptoms of infections. If a serious infection occurs, administer appropriate treatment and consider withholding efgartigimod alfa and hyaluronidase-qvfc 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 efgartigimod alfa and hyaluronidase-qvfc. The safety of immunization with live vaccines and the immune response to vaccination during treatment with efgartigimod alfa and hyaluronidase-qvfc are unknown. Because efgartigimod alfa and hyaluronidase-qvfc causes a reduction in IgG levels, vaccination with live vaccines is not recommended during treatment with efgartigimod alfa and hyaluronidase-qvfc.

Hypersensitivity reactions

In clinical trials, hypersensitivity reactions, including rash, angioedema, and dyspnea, were observed in patients treated with efgartigimod alfa and hyaluronidase-qvfc or intravenous efgartigimod alfa-fcab. Urticaria was also observed in patients treated with efgartigimod alfa and hyaluronidase-qvfc. Hypersensitivity reactions were mild or moderate and occurred within 1 hour to 3 weeks of administration.

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.

Monitor for clinical signs and symptoms of hypersensitivity reactions for at least 30 minutes after administration. If a hypersensitivity reaction occurs, the healthcare professional should institute appropriate measures if needed, or the patient should seek medical attention. Efgartigimod alfa and hyaluronidase-qvfc is contraindicated in patients with a history of serious hypersensitivity to efgartigimod alfa products, to hyaluronidase, or to any of the excipients of efgartigimod alfa and hyaluronidase-qvfc.

Infusion or injection-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/injection-related reaction occurs, initiate appropriate therapy. Consider the risks and benefits of readministering efgartigimod alfa and hyaluronidase-qvfc following a severe infusion/injection-related reaction. If a mild to moderate infusion/injection-related reaction occurs, patients may be rechallenged with close clinical observation, slower infusion/injection rates, and pre-medications.

Adverse reactions

The following clinically significant adverse reactions are described elsewhere in the labeling:

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.

Clinical experience in patients with generalized myasthenia gravis. The safety of efgartigimod alfa in patients with generalized myasthenia gravis was established in a double-blinded placebo-controlled study with efgartigimod alfa-fcab administered intravenously (Study 1) and its open-label extension, and in an active-controlled study of efgartigimod alfa and hyaluronidase-qvfc administered subcutaneously (Study 2) and its open-label extension.

Adverse reactions with efgartigimod alfa-fcab intravenous in patients with generalized myasthenia gravis. In clinical studies, the safety of efgartigimod alfa-fcab administered intravenously has been evaluated in 246 patients with generalized myasthenia gravis who received at least one dose of efgartigimod alfa-fcab, including 57 patients exposed to at least seven treatment cycles and eight patients exposed to at least 10 treatment cycles.

In a placebo-controlled study (Study 1) in patients with generalized myasthenia gravis, 84 patients received efgartigimod alfa-fcab 10 mg/kg. 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 50 days from the start of the previous treatment cycle. On average, efgartigimod alfa-fcab-treated patients received two cycles in Study 1. The mean and median times to the second treatment cycle were 94 days and 72 days from the initial infusion of the first treatment cycle, respectively, for efgartigimod alfa-fcab-treated patients.

Adverse reactions reported in at least 5% of patients treated with efgartigimod alfa-fcab and more frequently than placebo are summarized in Table 1. The most common adverse reactions (reported in at least 10% of efgartigimod alfa-fcab-treated patients) were respiratory tract infection, headache, and urinary tract infection.

Table 1. Adverse Reactions in at least 5% of Patients with Generalized Myasthenia Gravis Treated with Efgartigimod Alfa-fcab Intravenously (EFG IV) and More Frequently than in Placebo-Treated Patients in Study 1 (Safety Population)

Adverse reactions with efgartigimod alfa and hyaluronidase-qvfc in patients with generalized myasthenia gravis. In an active-controlled study in patients with generalized myasthenia gravis (Study 2), 110 patients were randomized and received one cycle of once-weekly administrations for 4 weeks (four administrations total) of either efgartigimod alfa and hyaluronidase-qvfc subcutaneously (n=55) or efgartigimod alfa-fcab intravenously (n=55) at recommended doses. The open-label extension of Study 2 included some patients who switched from efgartigimod alfa-fcab IV to efgartigimod alfa and hyaluronidase-qvfc.

The most common adverse reactions (reported in at least 10% of efgartigimod alfa and hyaluronidase-qvfc-treated patients) were injection site reactions and headache.

In Study 2, injection site reactions occurred in 38% of patients receiving efgartigimod alfa and hyaluronidase-qvfc. These were injection site rash, erythema, pruritus, bruising, pain, and urticaria.

In Study 2 and its open-label extension (n = 168), 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.

Clinical experience in patients with chronic inflammatory demyelinating polyneuropathy.

Adverse reactions with efgartigimod alfa and hyaluronidase-qvfc in patients with chronic inflammatory demyelinating polyneuropathy. In a placebo-controlled study in patients with chronic inflammatory demyelinating polyneuropathy (Study 3, stage B), 221 patients were randomized to receive once-weekly administration of either efgartigimod alfa and hyaluronidase-qvfc 1,008 mg /11, 200 units subcutaneously (n=111) or placebo (n=110). The mean duration of treatment with efgartigimod alfa and hyaluronidase-qvfc in stage B was 25 weeks. The overall safety profile observed in patients with chronic inflammatory demyelinating polyneuropathy treated with efgartigimod alfa and hyaluronidase-qvfc was consistent with the known safety profile of efgartigimod alfa and hyaluronidase-qvfc and of efgartigimod alfa-fcab administered intravenously.

In Study 3, injection site reactions occurred in 15% of patients treated with efgartigimod alfa and hyaluronidase-qvfc compared to 6% of patients who received placebo. The most common of these injection site reactions were injection site bruising and injection site erythema. All injection site reactions were mild to moderate in severity. Most injection site reactions occurred during the first 3 months of treatment.

Postmarketing experience

The following adverse reactions have been identified during postapproval use of efgartigimod alfa products. 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/injection-related reactions.

Drug interactions

Effect of efgartigimod alfa and hyaluronidase-qvfc on other drugs

Concomitant use of efgartigimod alfa and hyaluronidase-qvfc with medications that bind to the human neonatal Fc receptor (FcRn) (eg, immunoglobulin products, monoclonal antibodies, or antibody derivatives containing the human Fc domain of the IgG subclass) may lower systemic exposures and reduce the 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 efgartigimod alfa and hyaluronidase-qvfc and using alternative therapies.

Use in specific populations

Pregnancy

Pregnancy exposure registry. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to efgartigimod alfa and hyaluronidase-qvfc during pregnancy. Healthcare providers and patients may call 1-855-272-6524 or go to https://www.Vyvgartpregnancy.c... to enroll in or to obtain information about the registry.

Risk summary. There are no available data on the use of efgartigimod alfa and hyaluronidase-qvfc or efgartigimod alfa-containing products during pregnancy. There was no evidence of adverse developmental outcomes following the intravenous administration of efgartigimod alfa 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 may be transmitted from the mother to the developing fetus.

As efgartigimod alfa and hyaluronidase-qvfc is expected to reduce maternal IgG antibody levels, a reduction in passive protection to the newborn is anticipated. Risk and benefits should be considered before administering live vaccines to infants exposed to efgartigimod alfa and hyaluronidase-qvfc in utero.

Data.

Animal data. Efgartigimod alfa and hyaluronidase-qvfc for subcutaneous injection contains efgartigimod alfa and hyaluronidase.

Lactation

Risk summary. There is no information regarding the presence of efgartigimod alfa or hyaluronidase, from administration of efgartigimod alfa and hyaluronidase-qvfc, in human milk, the effects on the breastfed infant, or the effects on milk production. Maternal IgG is known to be present in human milk.

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for efgartigimod alfa and hyaluronidase-qvfc and any potential adverse effects on the breastfed infant from efgartigimod alfa and hyaluronidase-qvfc or from the underlying maternal condition.

Pediatric use

Safety and effectiveness in pediatric patients have not been established.

Geriatric use

Clinical studies of efgartigimod alfa and hyaluronidase-qvfc did not include sufficient numbers of patients aged 65 and older to determine whether they respond differently from younger adult patients.

Renal impairment

No dose adjustment of efgartigimod alfa and hyaluronidase-qvfc 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 the pharmacokinetic parameters of efgartigimod alfa and hyaluronidase-qvfc.

Clinical pharmacology

Mechanism of action

Efgartigimod alfa and hyaluronidase-qvfc is a coformulation of efgartigimod alfa and hyaluronidase.

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

Hyaluronidase increases the permeability of the subcutaneous tissue by depolymerizing hyaluronan. This effect is transient, and he permeability of the subcutaneous tissue is restored within 24 to 48 hours.

Pharmacodynamics

In Study 1, the pharmacological effect of efgartigimod alfa-fcab was assessed by measuring the decrease in serum IgG levels and AChR autoantibody levels. In patients testing positive for AChR antibodies and who were treated with efgartigimod alfa-fcab intravenously, there was a reduction in total IgG levels relative to baseline. A decrease in AChR autoantibody levels followed a similar pattern. A decrease in AChR-Ab was associated with a clinical response in AChR-Ab-positive patients, as measured by the change from baseline in MG-ADL total score.

In Study 2, the pharmacological effect of efgartigimod alfa and hyaluronidase-qvfc administered subcutaneously (SC) at 1,008 mg/11,200 Units was compared to efgartigimod alfa-fcab administered intravenously at 10 mg/kg (EFG IV) in generalized myasthenia gravis patients. The maximum mean reduction in AChR-Ab level was observed at week 4, with a mean reduction of 62.2% and 59.7% in the efgartigimod alfa and hyaluronidase-qvfc SC and efgartigimod alfa-fcab IV arm, respectively. The decrease in total IgG levels followed a similar pattern. The 90% confidence intervals for the geometric mean ratios of AChR-Ab reduction at day 29 and AUEC0-4w (area under the effect-time curve from time 0 to 4 weeks post-dose) were within the range of 80% to 125%, indicating no clinically significant difference between the two formulations.

Pharmacokinetics

Efgartigimod alfa exposures were approximately dose-proportional up to the highest subcutaneously tested dose of efgartigimod alfa and hyaluronidase-qvfc (1750 mg, 1.75 times the recommended dosage).

Absorption. The rate and extent of absorption from a single-dose prefilled syringe and a single-dose vial are similar.

Distribution. The volume of distribution is 15 to 20L.

Metabolism and elimination. Efgartigimod alfa and hyaluronidase are expected to be degraded by proteolytic enzymes into small peptides and amino acids.

The terminal half-life is 80 to 120 hours (3 to 5 days).

After a single intravenous dose of 10 mg/kg efgartigimod alfa-fcab in healthy subjects, less than 0.1% of the administered dose was recovered in urine.

Specific populations.

Age, sex, and race. A population pharmacokinetics analysis assessing the effects of age, body weight, sex, and race did not suggest any clinically significant impact of these covariates on efgartigimod alfa exposures.

Body weight. A population pharmacokinetics analysis suggests that the influence of body weight on efgartigimod alfa exposure after administration of efgartigimod alfa and hyaluronidase-qvfc SC 1008 mg was limited and not clinically relevant.

Patients with renal impairment. No dedicated pharmacokinetic study has been performed in patients with renal impairment.

Population PK analyses of data from the efgartigimod alfa and hyaluronidase-qvfc clinical studies indicated that patients with mild renal impairment (eGFR 60-89 mL/min/1.73 m²) had an 11% to 20% increase in exposure relative to the exposure in patients with normal renal function.

Patients with hepatic impairment. No dedicated pharmacokinetic study has been performed in patients with hepatic impairment. Hepatic impairment is not expected to affect the pharmacokinetics of efgartigimod alfa.

Drug interaction studies. Clinical drug interaction studies have not been performed with efgartigimod alfa.

P450 enzymes. Efgartigimod alfa is not metabolized by cytochrome P450 enzymes; therefore, interactions with concomitant medications that are substrates, inducers, or inhibitors of cytochrome P450 enzymes are unlikely.

Drug interactions with other drugs or biological products. Efgartigimod alfa may decrease concentrations of compounds that bind to the human FcRn.

Immunogenicity

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 efgartigimod alfa and hyaluronidase-qvfc or of other efgartigimod products.

In Study 2, in up to 10 weeks following the initiation of a treatment period with 4 weekly administrations, the incidence of anti-efgartigimod alfa antibodies was 35% (19 of 55) following treatment with efgartigimod alfa and hyaluronidase-qvfc and 20% (11 or 55) in patients receiving intravenous efgartigimod alfa-fcab. For both intravenous and subcutaneous arms, neutralizing anti-efgartigimod alfa antibodies were detected in 4% (2 of 55) of patients.

In Study 3, in up to 12 weeks of treatment in stage A and 48 weeks in stage B, the incidence of anti-efgartigimod alfa antibodies was 6% (20 of 317) in stage A and 2% (2 of 111) in stage B, following treatment with efgartigimod alfa and hyaluronidase-qvfc. Neutralizing anti-efgartigimod alfa antibodies were detected in 0.3% (1 of 317) of patients in stage A and in no patient in stage B.

Some neutralizing antibodies may not be detected by the assay. The available data are too limited to make definitive conclusions regarding immunogenicity and the effect on pharmacokinetics, safety, or efficacy of efgartigimod alfa and hyaluronidase-qvfc.

Nonclinical toxicology

Carcinogenesis, mutagenesis, impairment of fertility

Efgartigimod alfa and hyaluronidase-qvfc for subcutaneous injection contains efgartigimod alfa and hyaluronidase.

Carcinogenesis and mutagenesis. No studies have been conducted to assess the carcinogenic potential of efgartigimod alfa.

No studies have been conducted to assess the genotoxic potential of efgartigimod alfa.

No carcinogenicity or genotoxicity studies were conducted for human recombinant hyaluronidase.

Impairment of fertility. Intravenous administration of efgartigimod alfa (0, 30, or 100 mg/kg/day) to male and female rats before and during mating and continuing in females through gestation day 7 resulted in no adverse effects on fertility. Efgartigimod alfa exposures at the highest no-effect dose were approximately 12 times that in humans at the recommended human dose of 1008 mg. There were no effects on reproductive tissues in monkeys following subcutaneous administration of hyaluronidase (human recombinant) doses up to approximately 1,200 times the dose of hyaluronidase at the recommended human dose of efgartigimod alfa and hyaluronidase-qvfc (1,008 mg efgartigimod alfa and 11,200 U hyaluronidase) on a U/kg basis for 39 weeks. No systemic exposure to hyaluronidase was observed at doses up to approximately 120 times the dose of hyaluronidase at the recommended human dose of efgartigimod alfa and hyaluronidase-qvfc, on a U/kg basis.

Cinical studies

Generalized myasthenia gravis

Study 1 (described below), which established the effectiveness of efgartigimod alfa-fcab for the treatment of generalized myasthenia gravis in adults who are AChR antibody-positive, was conducted with the efgartigimod alfa-fcab intravenous formulation. In Study 2, efgartigimod alfa and hyaluronidase-qvfc demonstrated a comparable pharmacodynamic effect on AChR antibody reduction as compared to the efgartigimod alfa-fcab intravenous formulation, which established the efficacy of efgartigimod alfa and hyaluronidase-qvfc.

Study 1 (efgartigimod alfa-fcab intravenous). The efficacy of efgartigimod alfa-fcab intravenous (EFG IV) for the treatment of generalized myasthenia gravis in adults who are AChR antibody positive was established in a 26-week, multicenter, randomized, double-blind, placebo-controlled trial (Study 1; NCT03669588).

Study 1 enrolled patients who met the following criteria at screening:

A total of 167 patients were enrolled in Study 1 and were randomized to receive either EFG IV 10mg/kg (1200 mg for those weighing 120 kg or more) (n=84) or placebo (n=83). Baseline characteristics were similar between treatment groups. Patients had a median age of 46 years at screening (range: 19 to 81 years) and a median time since diagnosis of 7 years. Seventy-one percent were female, and 84% were White. Median MG-ADL total score was 9, and median quantitative myasthenia gravis total score was 16. The majority of patients (n=65 for EFG IV; n=64 for placebo) were positive for AChR antibodies.

At baseline, over 80% of patients in each group received AChE inhibitors, over 70% in each treatment group received steroids, and approximately 60% in each treatment group received nonsteroidal immunosuppressive therapies at stable doses.

Patients were treated with 10 mg/kg EFG IV administered as an intravenous infusion over one hour once weekly for 4 weeks. In patients weighing 120 kg or more, EFG IV was administered as 1200 mg per infusion. Subsequent treatment cycles were administered based on clinical evaluation, but no sooner than 50 days from the start of the previous treatment cycle.

The efficacy of EFG IV was measured using the Myasthenia Gravis-Specific Activities of Daily Living scale (MG-ADL), which assesses the impact of generalized myasthenia gravis on daily functions of eight signs or symptoms that are typically affected in generalized myasthenia gravis. Each item is assessed on a 4-point scale where a score of 0 represents normal function and a score of 3 represents loss of ability to perform that function. A total score ranges from 0 to 24, with the higher scores indicating more impairment. In this study, an MG-ADL responder was defined as a patient with a 2-point or greater reduction in the total MG-ADL score compared to the treatment cycle baseline for at least 4 consecutive weeks, with the first reduction occurring no later than 1 week after the last infusion of the cycle.

The primary efficacy endpoint was the comparison of the percentage of MG-ADL responders during the first treatment cycle between treatment groups in the AChR-Ab positive population. A statistically significant difference favoring EFG IV was observed in the MG-ADL responder rate during the first treatment cycle (67.7% in the EFG IV-treated group vs 29.7% in the placebo-treated group [p <0.0001]).

The efficacy of EFG IV was also measured using the Quantitative Myasthenia Gravis (QMG) total score, which is a 13-item categorical grading system that assesses muscle weakness. Each item is assessed on a 4-point scale where a score of 0 represents no weakness and a score of 3 represents severe weakness. A total possible score ranges from 0 to 39, where higher scores indicate more severe impairment. In this study, a QMG responder was defined as a patient who had a 3-point or greater reduction in the total QMG score compared to the treatment cycle baseline for at least 4 consecutive weeks, with the first reduction occurring no later than 1 week after the last infusion of the cycle.

The secondary endpoint was the comparison of the percentage of QMG responders during the first treatment cycle between both treatment groups in the AChR-Ab positive patients. A statistically significant difference favoring EFG IV was observed in the QMG responder rate during the first treatment cycle (63.1% in the EFG IV-treated group vs 14.1% in the placebo-treated group [p <0.0001]).

For details of study results, see the Clinical Studies section of the DAILYMED drug label information.

Chronic inflammatory demyelinating polyneuropathy

The efficacy of efgartigimod alfa and hyaluronidase-qvfc for the treatment of adults with chronic inflammatory demyelinating polyneuropathy was established in a two-stage, multicenter study (Study 3; NCT04281472). Study 3 included an open-label period to identify efgartigimod alfa and hyaluronidase-qvfc responders (stage A) who then entered a randomized, double-blind, placebo-controlled, withdrawal period (stage B).

Study 3 enrolled male and female patients aged 18 years and older, who at the time of screening, had a documented diagnosis of definite or probable chronic inflammatory demyelinating polyneuropathy using the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS, 2010) criteria for progressing or relapsing forms.

The Inflammatory Neuropathy Cause and Treatment disability score (INCAT) is a scale used to assess the impact of chronic inflammatory demyelinating polyneuropathy on daily upper and lower limb function, and is composed of the arm score and leg score (0 to 5 points for each). A total score on the INCAT ranges from 0 to 10 points, with a higher number representing more disability. The adjusted INCAT (aINCAT) disability score, identical to the INCAT disability score but with changes in the upper limb function from 0 (normal) to 1 (minor symptoms) excluded, was used to assess efficacy for efgartigimod alfa and hyaluronidase-qvfc for the treatment of chronic inflammatory demyelinating polyneuropathy.

Stage A. In stage A, a total of 322 patients received up to 12 once-weekly subcutaneous injections of efgartigimod alfa and hyaluronidase-qvfc 1008 mg/11,200 units until evidence of improvement occurred at two consecutive study visits. Improvement was defined as aINCAT improvement of 1 or more points, I-RODS improvement of 4 or more points, or a mean grip strength improvement of 8 or more kPa. Stage A included 228 patients currently receiving standard-of-care therapy and 94 patients who had either not received prior treatment for chronic inflammatory demyelinating polyneuropathy or were not treated with standard-of-care therapy for at least 6 months before study entry. Sixty-nine percent of patients (n=221) who had documented improvement at two consecutive visits during Stage A then entered Stage B.

Stage B. In stage B, a total of 221 patients were randomized to receive once-weekly subcutaneous injections of efgartigimod alfa and hyaluronidase-qvfc 1008 mg/11,200 units (n=111) or placebo (n=110).

Baseline characteristics of patients in stage B were similar between treatment groups. Patients had a median age of 55 years (range: 20 to 82 years), a median time since chronic inflammatory demyelinating polyneuropathy diagnosis of 2.2 years, and a median INCAT score of 3.0. Sixty-four percent were male and 65% were White, 30% Asian, and 1% African American.

Stage B included 146 patients currently receiving standard-of-care therapy and 75 patients who had either not received prior treatment for chronic inflammatory demyelinating polyneuropathy or were not treated with standard-of-care therapy for at least 6 months before study entry.

The primary endpoint was the time to clinical deterioration, defined as a 1-point increase in aINCAT at two consecutive visits or a more than 1-point increase in aINCAT at one visit. Patients who had clinical deterioration or completed week 48 in Stage B without clinical deterioration were withdrawn from the placebo-controlled portion of the study. The study stopped when 88 events of clinical deterioration occurred for the primary endpoint analysis.

Patients who received efgartigimod alfa and hyaluronidase-qvfc experienced a longer time to clinical deterioration (ie, increase of ≥1 point in aINCAT score) compared to patients who received placebo, which was statistically significant, as demonstrated by a hazard ratio of 0.394 (95% CI [0.253; 0.614] p<0.0001). The results are presented in Table 3 and Figure 3.

For details of Study 3 results, see the Clinical Studies section of the DAILYMED drug label information.

How supplied/storage and handling

Efgartigimod alfa and hyaluronidase-qvfc (efgartigimod alfa and hyaluronidase-qvfc) injection is a preservative-free, sterile, yellowish, clear to opalescent solution supplied as a single-dose prefilled syringe or vial.

Single-dose prefilled syringe. Each single-dose prefilled syringe contains 1,000 mg efgartigimod alfa and 10,000 units hyaluronidase per 5 mL (200 mg/2,000 units per mL). It is available in cartons of one or four single-dose prefilled syringes (NDC 73475-1221-1 or NDC 73475-1221-4). The safety needle that is 25G, 5/8 inches in length, and thin-wall type is not included in the carton.

Store efgartigimod alfa and hyaluronidase-qvfc prefilled syringe 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.

If needed, prefilled syringes may be stored at room temperature at up to 30°C (86°F) in the original carton for a single period of up to 30 days after removing from the refrigerator or until the expiration date on the carton, whichever occurs first. Record the date removed from the refrigerator on the carton.

Single-dose vial. Each single-dose vial contains 1,008 mg efgartigimod alfa and 11,200 units hyaluronidase per 5.6 mL (180 mg/2,000 units per mL). It is available in cartons of one single-dose vial (NDC 73475-3102-3).

Store efgartigimod alfa and hyaluronidase-qvfc 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.

If needed, unopened vials may be stored in the original carton for up to 3 days at room temperature at 20°C to 25°C (68°F to 77°F) for a single period before administration or returned to refrigeration. Do not store the vial at room temperature more than once. Record the date removed from and the date returned to the refrigerator on the carton.

Patient counseling information

Advise the patient and/or caregiver to read FDA-approved patient labeling.

Infections. Instruct patients to communicate any history of infections to the healthcare provider and to contact their healthcare provider if they develop symptoms of an infection. Advise patients to complete age-appropriate vaccines according to immunization guidelines before initiation of a new treatment cycle with efgartigimod alfa and hyaluronidase-qvfc. Administration of live vaccines is not recommended during treatment with efgartigimod alfa and hyaluronidase-qvfc.

Hypersensitivity reactions. Inform patients that hypersensitivity reactions, including angioedema and anaphylaxis, have occurred in patients who were treated with efgartigimod alfa products. Inform patients about the signs and symptoms of these reactions, and advise patients to contact their healthcare provider immediately if these occur.

Infusion/injection-related reactions. Advise patients of the potential risk of infusion/injection-related reactions, which can include hypertension, chills, shivering, and chest, abdominal, and back pain.

Instructions on injection technique. If a patient or caregiver is to administer subcutaneous efgartigimod alfa and hyaluronidase-qvfc prefilled syringe, instruct them in proper injection technique (eg, site selection and duration of injection).

Pregnancy registry. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to efgartigimod alfa and hyaluronidase-qvfc during pregnancy. Encourage participation and advise patients about how they may enroll in the registry.