These Highlights Do Not Include All The Information Needed To Use Vyvgart Hytrulo Safely And Effectively. See Full Prescribing Information For Vyvgart Hytrulo.

Single-Dose Prefilled Syringe

VYVGART HYTRULO prefilled syringe may be administered by patients and/or caregivers after proper instruction in subcutaneous injection technique [see Instructions for Use].

Store VYVGART HYTRULO 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 one time. Record the date removed from and the date returned to the refrigerator on the carton.

VYVGART HYTRULO is a fixed-combination drug product containing efgartigimod alfa and hyaluronidase (human recombinant).

Efgartigimod alfa, a neonatal Fc receptor blocker, is a human immunoglobulin G1 (IgG1) -derived Fc fragment (fragment, crystallized) of the za allotype, produced in Chinese hamster ovary (CHO) cells. The efgartigimod alfa Fc fragment is a homodimer consisting of two identical peptide chains each consisting of 227 amino acids linked together by two interchain disulfide bonds with affinity for FcRn. The molecular weight of efgartigimod alfa is approximately 54 kDa.

Hyaluronidase (human recombinant) is an endoglycosidase used to increase the dispersion and absorption of co-administered drugs when administered subcutaneously. Hyaluronidase (human recombinant) is a glycosylated single-chain protein produced by Chinese hamster ovary cells containing a DNA plasmid encoding for a soluble fragment of human hyaluronidase (PH20). Hyaluronidase (human recombinant) has a molecular weight of approximately 61 kDa.

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

Each 5 mL single-dose prefilled syringe contains 1,000 mg of efgartigimod alfa and 10,000 units of hyaluronidase (human recombinant). Each mL contains 200 mg of efgartigimod alfa, 2,000 units of hyaluronidase (human recombinant) and arginine hydrochloride (10.5 mg), histidine (1.4 mg), L-histidine hydrochloride monohydrate (2.2 mg), methionine (1.5 mg), polysorbate 80 (0.4 mg), sodium chloride (4.1 mg), sucrose (20.5 mg), and Water for Injection, USP, at a pH of 6.0.

Each 5.6 mL single-dose vial contains 1,008 mg of efgartigimod alfa and 11,200 units of hyaluronidase (human recombinant). Each mL contains 180 mg of efgartigimod alfa, 2,000 units of hyaluronidase (human recombinant) and

• -
  histidine (1.4 mg), L- histidine hydrochloride monohydrate (2.2 mg), methionine (1.5 mg), polysorbate 20 (0.4 mg), sodium chloride (5.8 mg), sucrose (20.5 mg), and Water for Injection, USP, at a pH of 6.0 or
• -
  arginine hydrochloride (10.5 mg), histidine (1.4 mg), L- histidine hydrochloride monohydrate (2.2 mg), methionine (1.5 mg), polysorbate 80 (0.4 mg), sodium chloride (4.1 mg), sucrose (20.5 mg), and Water for Injection, USP, at a pH of 6.0.

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 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) [see Adverse Reactions (6.1) and Clinical Studies (14)]. 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 VYVGART HYTRULO administration in patients with an active infection until the infection is resolved. During treatment with VYVGART HYTRULO, monitor for clinical signs and symptoms of infections. If serious infection occurs, administer appropriate treatment and consider withholding VYVGART HYTRULO until the infection has resolved.

Safety and effectiveness in pediatric patients have not been established.

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

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 HYTRULO 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% (19/55) following treatment with VYVGART HYTRULO and 20% (11/55) in patients receiving intravenous efgartigimod alfa-fcab. For both IV and SC arms, neutralizing anti-efgartigimod alfa antibodies were detected in 4% (2/55) 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% (20/317) in stage A and 2% (2/111) in stage B, following treatment with VYVGART HYTRULO. Neutralizing anti-efgartigimod alfa antibodies were detected in 0.3% (1/317) 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 VYVGART HYTRULO.

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

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/Injection-Related Reactions [see Warnings and Precautions (5.3)]

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 HYTRULO and using alternative therapies. (7)

No dose adjustment of VYVGART HYTRULO 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 VYVGART HYTRULO [see Clinical Pharmacology (12.3)].

VYVGART HYTRULO [viv' gart hye troo' loe]

(efgartigimod alfa and hyaluronidase-qvfc)

injection, for subcutaneous use

1,000 mg and 10,000 units/5 mL

This Instructions for Use contains information on how to inject VYVGART HYTRULO.

Important Information You Need to Know Before Injecting VYVGART HYTRULO

• VYVGART HYTRULO is for under the skin (subcutaneous) injection only.
• Be sure to read and understand this Instructions for Use before injecting VYVGART HYTRULO. Your healthcare provider should show you or your caregiver how to prepare and inject VYVGART HYTRULO the correct way before using it for the first time. Ask your healthcare provider if you have any questions.
• The prefilled syringe is for one-time-use only and cannot be reused.
• Do not use VYVGART HYTRULO if it has been at room temperature for longer than 30 days.
• Do not use the prefilled syringe if it is expired.
• Do not use the prefilled syringe if it is cracked, broken, or damaged. Return damaged prefilled syringes to the specialty pharmacy.
• Do not use a prefilled syringe if the liquid medicine is discolored or contains particles. The liquid medicine should look clear to yellowish in color. A little cloudiness is normal.
• Do not shake the prefilled syringe.
• You will need supplies that are not provided with VYVGART HYTRULO (see Figure J).

Storing VYVGART HYTRULO Prefilled Syringe

Prefilled Syringe Parts

Gather and Check the Prefilled Syringe

Prepare for the Injection

Inject VYVGART HYTRULO

Throw away (dispose of) the Used Prefilled Syringe

Additional Disposal Information

Additional Information

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 AChR autoantibody levels. In patients testing positive for AChR antibodies and who were treated with efgartigimod alfa-fcab intravenous, there was a reduction in total IgG levels relative to baseline. 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 VYVGART HYTRULO 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 gMG 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 VYVGART HYTRULO 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 AUEC_0-4w (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.

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

VYVGART HYTRULO is indicated for the treatment of adult patients with:

• generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody positive
• chronic inflammatory demyelinating polyneuropathy (CIDP)

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

• Infections: Delay administration of VYVGART HYTRULO to patients with an active infection. Monitor for signs and symptoms of infection in patients treated with VYVGART HYTRULO. If serious infection occurs, administer appropriate treatment and consider withholding VYVGART HYTRULO until the infection has resolved. (5.1)
• Hypersensitivity Reactions: Anaphylaxis, hypotension leading to syncope, angioedema, dyspnea, rash, and urticaria have occurred in patients treated with VYVGART HYTRULO or intravenous efgartigimod alfa-fcab product. 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/injection-Related Reactions: If a severe infusion/injection-related reaction occurs, initiate appropriate therapy; consider the risks and benefits of readministering. If a mild to moderate infusion/injection-related reaction occurs, may rechallenge with close clinical observation, slower infusion/injection rates, and pre-medications. (5.3)

• See Full Prescribing Information for instructions on dosage, preparation, and administration. (2.1, 2.2, 2.3, 2.4, 2.5)
• Evaluate the need to administer age-appropriate vaccines according to immunization guidelines before initiation of a new treatment cycle with VYVGART HYTRULO. (2.1)
• Important Administration Information
  • VYVGART HYTRULO is for subcutaneous use only. (2.2)
  • Prefilled syringe can be administered by patients and/or caregivers. (2.2)
  • Vial to be administered with a winged infusion set by a healthcare professional only. (2.2)
• gMG: recommended dose and dose schedule
  • Administer in cycles of once weekly injections for 4 weeks. (2.3)
  • Prefilled syringe: 1,000 mg efgartigimod alfa and 10,000 units hyaluronidase administered over 20 to 30 seconds. (2.3)
  • Vial: 1,008 mg efgartigimod alfa and 11,200 units hyaluronidase over 30 to 90 seconds. (2.3)
  • Administer subsequent treatment cycles based on clinical evaluation. (2.3)
• CIDP: recommended dose and dose schedule
  • Administer as once weekly injections. (2.4)
  • Prefilled syringe: 1,000 mg efgartigimod alfa and 10,000 units hyaluronidase administered over approximately 20 to 30 seconds. (2.4)
  • Vial: 1,008 mg efgartigimod alfa and 11,200 units hyaluronidase over 30 to 90 seconds. (2.4)

Evaluate the need to administer age-appropriate vaccines according to immunization guidelines before initiation of a new treatment cycle with VYVGART HYTRULO. Because VYVGART HYTRULO causes transient reduction in IgG levels, vaccination with live vaccines is not recommended during treatment with VYVGART HYTRULO [see Dosage and Administration (2.3) and Warnings and Precautions (5.1)].

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

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 [see Warnings and Precautions (5.2, 5.3)].

Neurological: There have been reports of worsening of symptoms and signs of CIDP when transitioning from intravenous immunoglobulin treatments to VYVGART HYTRULO [see Drug Interactions (7.1)].

In clinical trials, hypersensitivity reactions, including rash, angioedema, and dyspnea were observed in patients treated with VYVGART HYTRULO or intravenous efgartigimod alfa-fcab. Urticaria was also observed in patients treated with VYVGART HYTRULO. Hypersensitivity reactions were mild or moderate, occurred within one hour to three 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 [see Dosage and Administration (2.4)]. If a hypersensitivity reaction occurs, the healthcare professional should institute appropriate measures if needed or the patient should seek medical attention. VYVGART HYTRULO is contraindicated in patients with a history of serious hypersensitivity to efgartigimod alfa products, to hyaluronidase, or to any of the excipients of VYVGART HYTRULO [see Contraindications (4)].

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.

Advise the patient and/or caregiver to read FDA-approved patient labeling (Patient Information and Instructions for Use).

Study 1 (described below) which established the effectiveness of efgartigimod alfa-fcab for the treatment of generalized myasthenia gravis (gMG) in adults who are AChR antibody positive was conducted with efgartigimod alfa-fcab intravenous formulation. In Study 2, VYVGART HYTRULO demonstrated a comparable pharmacodynamic effect on AChR antibody reduction as compared to the efgartigimod alfa-fcab intravenous formulation, which established the efficacy of VYVGART HYTRULO [see Clinical Pharmacology (12.2)].

VYVGART HYTRULO (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.

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 VYVGART HYTRULO 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.

Concomitant use of VYVGART HYTRULO 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 HYTRULO and using alternative therapies.

NDC 73475-3102-3

VYVGART^® Hytrulo

(efgartigimod alfa and

hyaluronidase-qvfc)

INJECTION

1,008 mg and 11,200 units/5.6 mL

(180 mg and 2,000 units/mL)

For subcutaneous injection

over 30 to 90 seconds

One single-dose vial

Discard unused portion

Must be administered by

a healthcare provider

Rx only

NDC 73475-1221-1

VYVGART Hytrulo^®

(efgartigimod alfa and hyaluronidase-qvfc)

INJECTION

1,000 mg and 10,000 units/5 mL

(200 mg and 2,000 units/mL)

For subcutaneous injection over 20 to 30 seconds

One single-dose prefilled syringe

Rx only

VYVGART HYTRULO is for subcutaneous use only. Do not administer intravenously. Do not dilute VYVGART HYTRULO.

The efficacy of VYVGART HYTRULO for the treatment of adults with chronic inflammatory demyelinating polyneuropathy (CIDP) was established in a two stage, multicenter study (Study 3; NCT04281472). Study 3 included a run-in period of up to 12 weeks after withdrawal of existing treatment for CIDP in order to identify patients with active disease, followed by an open-label period to identify VYVGART HYTRULO responders (stage A) who then entered a randomized, double-blind, placebo-controlled, withdrawal period (stage B).

Study 3 enrolled male and female patients age 18 years and older, who at the time of screening, had a documented diagnosis of definite or probable CIDP 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 CIDP 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 VYVGART HYTRULO for the treatment of CIDP.

VYVGART HYTRULO for subcutaneous injection contains efgartigimod alfa and hyaluronidase [see Description (11)].

NDC 73475-3102-3

VYVGART^® Hytrulo

(efgartigimod alfa and

hyaluronidase-qvfc)

INJECTION

1,008 mg and 11,200 units/5.6 mL

(180 mg and 2,000 units/mL)

For subcutaneous injection

over 30 to 90 seconds

One single-dose vial

Discard unused portion

Must be administered by

a healthcare provider

Rx only

Single-Dose Prefilled Syringe

VYVGART HYTRULO prefilled syringe may be administered by patients and/or caregivers after proper instruction in subcutaneous injection technique [see Instructions for Use].

Store VYVGART HYTRULO 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 one time. Record the date removed from and the date returned to the refrigerator on the carton.

VYVGART HYTRULO is a fixed-combination drug product containing efgartigimod alfa and hyaluronidase (human recombinant).

Efgartigimod alfa, a neonatal Fc receptor blocker, is a human immunoglobulin G1 (IgG1) -derived Fc fragment (fragment, crystallized) of the za allotype, produced in Chinese hamster ovary (CHO) cells. The efgartigimod alfa Fc fragment is a homodimer consisting of two identical peptide chains each consisting of 227 amino acids linked together by two interchain disulfide bonds with affinity for FcRn. The molecular weight of efgartigimod alfa is approximately 54 kDa.

Hyaluronidase (human recombinant) is an endoglycosidase used to increase the dispersion and absorption of co-administered drugs when administered subcutaneously. Hyaluronidase (human recombinant) is a glycosylated single-chain protein produced by Chinese hamster ovary cells containing a DNA plasmid encoding for a soluble fragment of human hyaluronidase (PH20). Hyaluronidase (human recombinant) has a molecular weight of approximately 61 kDa.

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

Each 5 mL single-dose prefilled syringe contains 1,000 mg of efgartigimod alfa and 10,000 units of hyaluronidase (human recombinant). Each mL contains 200 mg of efgartigimod alfa, 2,000 units of hyaluronidase (human recombinant) and arginine hydrochloride (10.5 mg), histidine (1.4 mg), L-histidine hydrochloride monohydrate (2.2 mg), methionine (1.5 mg), polysorbate 80 (0.4 mg), sodium chloride (4.1 mg), sucrose (20.5 mg), and Water for Injection, USP, at a pH of 6.0.

Each 5.6 mL single-dose vial contains 1,008 mg of efgartigimod alfa and 11,200 units of hyaluronidase (human recombinant). Each mL contains 180 mg of efgartigimod alfa, 2,000 units of hyaluronidase (human recombinant) and

• -
  histidine (1.4 mg), L- histidine hydrochloride monohydrate (2.2 mg), methionine (1.5 mg), polysorbate 20 (0.4 mg), sodium chloride (5.8 mg), sucrose (20.5 mg), and Water for Injection, USP, at a pH of 6.0 or
• -
  arginine hydrochloride (10.5 mg), histidine (1.4 mg), L- histidine hydrochloride monohydrate (2.2 mg), methionine (1.5 mg), polysorbate 80 (0.4 mg), sodium chloride (4.1 mg), sucrose (20.5 mg), and Water for Injection, USP, at a pH of 6.0.

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 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) [see Adverse Reactions (6.1) and Clinical Studies (14)]. 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 VYVGART HYTRULO administration in patients with an active infection until the infection is resolved. During treatment with VYVGART HYTRULO, monitor for clinical signs and symptoms of infections. If serious infection occurs, administer appropriate treatment and consider withholding VYVGART HYTRULO until the infection has resolved.

Safety and effectiveness in pediatric patients have not been established.

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

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 HYTRULO 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% (19/55) following treatment with VYVGART HYTRULO and 20% (11/55) in patients receiving intravenous efgartigimod alfa-fcab. For both IV and SC arms, neutralizing anti-efgartigimod alfa antibodies were detected in 4% (2/55) 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% (20/317) in stage A and 2% (2/111) in stage B, following treatment with VYVGART HYTRULO. Neutralizing anti-efgartigimod alfa antibodies were detected in 0.3% (1/317) 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 VYVGART HYTRULO.

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

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/Injection-Related Reactions [see Warnings and Precautions (5.3)]

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 HYTRULO and using alternative therapies. (7)

No dose adjustment of VYVGART HYTRULO 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 VYVGART HYTRULO [see Clinical Pharmacology (12.3)].

VYVGART HYTRULO [viv' gart hye troo' loe]

(efgartigimod alfa and hyaluronidase-qvfc)

injection, for subcutaneous use

1,000 mg and 10,000 units/5 mL

This Instructions for Use contains information on how to inject VYVGART HYTRULO.

Important Information You Need to Know Before Injecting VYVGART HYTRULO

• VYVGART HYTRULO is for under the skin (subcutaneous) injection only.
• Be sure to read and understand this Instructions for Use before injecting VYVGART HYTRULO. Your healthcare provider should show you or your caregiver how to prepare and inject VYVGART HYTRULO the correct way before using it for the first time. Ask your healthcare provider if you have any questions.
• The prefilled syringe is for one-time-use only and cannot be reused.
• Do not use VYVGART HYTRULO if it has been at room temperature for longer than 30 days.
• Do not use the prefilled syringe if it is expired.
• Do not use the prefilled syringe if it is cracked, broken, or damaged. Return damaged prefilled syringes to the specialty pharmacy.
• Do not use a prefilled syringe if the liquid medicine is discolored or contains particles. The liquid medicine should look clear to yellowish in color. A little cloudiness is normal.
• Do not shake the prefilled syringe.
• You will need supplies that are not provided with VYVGART HYTRULO (see Figure J).

Storing VYVGART HYTRULO Prefilled Syringe

Prefilled Syringe Parts

Gather and Check the Prefilled Syringe

Prepare for the Injection

Inject VYVGART HYTRULO

Throw away (dispose of) the Used Prefilled Syringe

Additional Disposal Information

Additional Information

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 AChR autoantibody levels. In patients testing positive for AChR antibodies and who were treated with efgartigimod alfa-fcab intravenous, there was a reduction in total IgG levels relative to baseline. 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 VYVGART HYTRULO 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 gMG 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 VYVGART HYTRULO 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 AUEC_0-4w (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.

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

VYVGART HYTRULO is indicated for the treatment of adult patients with:

• generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody positive
• chronic inflammatory demyelinating polyneuropathy (CIDP)

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

• Infections: Delay administration of VYVGART HYTRULO to patients with an active infection. Monitor for signs and symptoms of infection in patients treated with VYVGART HYTRULO. If serious infection occurs, administer appropriate treatment and consider withholding VYVGART HYTRULO until the infection has resolved. (5.1)
• Hypersensitivity Reactions: Anaphylaxis, hypotension leading to syncope, angioedema, dyspnea, rash, and urticaria have occurred in patients treated with VYVGART HYTRULO or intravenous efgartigimod alfa-fcab product. 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/injection-Related Reactions: If a severe infusion/injection-related reaction occurs, initiate appropriate therapy; consider the risks and benefits of readministering. If a mild to moderate infusion/injection-related reaction occurs, may rechallenge with close clinical observation, slower infusion/injection rates, and pre-medications. (5.3)

• See Full Prescribing Information for instructions on dosage, preparation, and administration. (2.1, 2.2, 2.3, 2.4, 2.5)
• Evaluate the need to administer age-appropriate vaccines according to immunization guidelines before initiation of a new treatment cycle with VYVGART HYTRULO. (2.1)
• Important Administration Information
  • VYVGART HYTRULO is for subcutaneous use only. (2.2)
  • Prefilled syringe can be administered by patients and/or caregivers. (2.2)
  • Vial to be administered with a winged infusion set by a healthcare professional only. (2.2)
• gMG: recommended dose and dose schedule
  • Administer in cycles of once weekly injections for 4 weeks. (2.3)
  • Prefilled syringe: 1,000 mg efgartigimod alfa and 10,000 units hyaluronidase administered over 20 to 30 seconds. (2.3)
  • Vial: 1,008 mg efgartigimod alfa and 11,200 units hyaluronidase over 30 to 90 seconds. (2.3)
  • Administer subsequent treatment cycles based on clinical evaluation. (2.3)
• CIDP: recommended dose and dose schedule
  • Administer as once weekly injections. (2.4)
  • Prefilled syringe: 1,000 mg efgartigimod alfa and 10,000 units hyaluronidase administered over approximately 20 to 30 seconds. (2.4)
  • Vial: 1,008 mg efgartigimod alfa and 11,200 units hyaluronidase over 30 to 90 seconds. (2.4)

Evaluate the need to administer age-appropriate vaccines according to immunization guidelines before initiation of a new treatment cycle with VYVGART HYTRULO. Because VYVGART HYTRULO causes transient reduction in IgG levels, vaccination with live vaccines is not recommended during treatment with VYVGART HYTRULO [see Dosage and Administration (2.3) and Warnings and Precautions (5.1)].

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

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 [see Warnings and Precautions (5.2, 5.3)].

Neurological: There have been reports of worsening of symptoms and signs of CIDP when transitioning from intravenous immunoglobulin treatments to VYVGART HYTRULO [see Drug Interactions (7.1)].

In clinical trials, hypersensitivity reactions, including rash, angioedema, and dyspnea were observed in patients treated with VYVGART HYTRULO or intravenous efgartigimod alfa-fcab. Urticaria was also observed in patients treated with VYVGART HYTRULO. Hypersensitivity reactions were mild or moderate, occurred within one hour to three 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 [see Dosage and Administration (2.4)]. If a hypersensitivity reaction occurs, the healthcare professional should institute appropriate measures if needed or the patient should seek medical attention. VYVGART HYTRULO is contraindicated in patients with a history of serious hypersensitivity to efgartigimod alfa products, to hyaluronidase, or to any of the excipients of VYVGART HYTRULO [see Contraindications (4)].

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.

Advise the patient and/or caregiver to read FDA-approved patient labeling (Patient Information and Instructions for Use).

Study 1 (described below) which established the effectiveness of efgartigimod alfa-fcab for the treatment of generalized myasthenia gravis (gMG) in adults who are AChR antibody positive was conducted with efgartigimod alfa-fcab intravenous formulation. In Study 2, VYVGART HYTRULO demonstrated a comparable pharmacodynamic effect on AChR antibody reduction as compared to the efgartigimod alfa-fcab intravenous formulation, which established the efficacy of VYVGART HYTRULO [see Clinical Pharmacology (12.2)].

VYVGART HYTRULO (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.

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 VYVGART HYTRULO 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.

Concomitant use of VYVGART HYTRULO 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 HYTRULO and using alternative therapies.

NDC 73475-3102-3

VYVGART^® Hytrulo

(efgartigimod alfa and

hyaluronidase-qvfc)

INJECTION

1,008 mg and 11,200 units/5.6 mL

(180 mg and 2,000 units/mL)

For subcutaneous injection

over 30 to 90 seconds

One single-dose vial

Discard unused portion

Must be administered by

a healthcare provider

Rx only

NDC 73475-1221-1

VYVGART Hytrulo^®

(efgartigimod alfa and hyaluronidase-qvfc)

INJECTION

1,000 mg and 10,000 units/5 mL

(200 mg and 2,000 units/mL)

For subcutaneous injection over 20 to 30 seconds

One single-dose prefilled syringe

Rx only

VYVGART HYTRULO is for subcutaneous use only. Do not administer intravenously. Do not dilute VYVGART HYTRULO.

The efficacy of VYVGART HYTRULO for the treatment of adults with chronic inflammatory demyelinating polyneuropathy (CIDP) was established in a two stage, multicenter study (Study 3; NCT04281472). Study 3 included a run-in period of up to 12 weeks after withdrawal of existing treatment for CIDP in order to identify patients with active disease, followed by an open-label period to identify VYVGART HYTRULO responders (stage A) who then entered a randomized, double-blind, placebo-controlled, withdrawal period (stage B).

Study 3 enrolled male and female patients age 18 years and older, who at the time of screening, had a documented diagnosis of definite or probable CIDP 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 CIDP 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 VYVGART HYTRULO for the treatment of CIDP.

VYVGART HYTRULO for subcutaneous injection contains efgartigimod alfa and hyaluronidase [see Description (11)].

NDC 73475-3102-3

VYVGART^® Hytrulo

(efgartigimod alfa and

hyaluronidase-qvfc)

INJECTION

1,008 mg and 11,200 units/5.6 mL

(180 mg and 2,000 units/mL)

For subcutaneous injection

over 30 to 90 seconds

One single-dose vial

Discard unused portion

Must be administered by

a healthcare provider

Rx only