Efgartigimod is an intravenous, first-in-class antibody fragment that binds to the neonatal Fc receptor (FcRn). The blockade of FcRn reduces IgG antibody concentrations, including the abnormal antiacetylcholine receptor (AChR) antibodies that are present in patients with generalized myasthenia gravis (gMG). In a 26-week randomized, double-blind, placebo-controlled trial of patients with gMG who were AchR antibody positive, significantly more patients treated with efgartigimod alfa were responders on the Myasthenia Gravis-Specific Activities of Daily Living scale (MG-ADL) and achieved greater reductions in scores from baseline compared to patients treated with placebo during the first treatment cycle (67.7% vs. 29.7%; p less than 0.0001). Patients who received efgartigimod alfa also reported greater improvements from baseline during the first treatment cycle on the Quantitative Myasthenia Gravis score (QMG), a categorical scale assessing muscle weakness (63.1% responders vs. 14.1% responders; p less than 0.0001). The FDA approved efgartigimod alfa in December 2021 under a fast-track designation and the product is designated as an orphan drug.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-For intravenous infusion only. Must be diluted before administration.
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Efgartigimod alfa is a clear to slightly opalescent and colorless to slightly yellow solution. Do not use if the solution is discolored or particles are present. Visually inspect the infusion solution before administration. Do not use the infusion if it is discolored or if opaque or foreign particles are seen.
Intravenous Administration
Infusion Preparation
-Dilute the appropriate dose with 0.9% Sodium Chloride Injection to a total volume of 125 mL. Discard any unused portion in the vials.
-Gently invert the bag to mix completely. Do NOT shake.
-Prepare the diluted infusion solution using polyethylene (PE), polyvinyl chloride (PVC), ethylene vinyl acetate (EVA), or ethylene/polypropylene copolymer bags (polyolefins bags).
-Storage: Following dilution, infuse within 4 hours. If immediate administration is not possible, refrigerate the diluted solution at 2 to 8 degrees C (36 to 46 degrees F) for up to 8 hours. Protect from light. Do not freeze. Prior to administration, allow the solution to warm to room temperature in ambient air. Complete the infusion within 4 hours following removal from refrigeration.
IV Infusion Administration
-Infuse over 1 hour via a 0.2 micron in-line filter.
-Only administer with PE, PVC, EVA, or polyurethane/polypropylene infusion lines.
-Do not mix efgartigimod alfa with other medications or inject other medications into infusion side ports.
-Flush the entire line with 0.9% Sodium Chloride Injection, USP following infusion.
-Monitor patients during and for 1 hour after the infusion for signs and symptoms of hypersensitivity reactions. If a hypersensitivity reaction occurs, institute appropriate therapy and discontinue efgartigimod alfa.
Efgartigimod alfa may increase the risk of infection or immunosuppression. Respiratory tract infection occurred in 33% of patients who received efgartigimod alfa 10 mg/kg (n = 84) compared to 29% of patients who received placebo (n = 83) during a clinical study in patients with generalized myasthenia gravis. Urinary tract infection occurred in 10% of patients who received efgartigimod alfa 10 mg/kg compared to 5% of patients who received placebo. On average, patients received 2 cycles of efgartigimod alfa, with mean and median times to the second treatment cycle of 94 and 72 days from the initial infusion of the first treatment cycle. Compared to placebo, more efgartigimod- treated patients experienced lower concentrations of white blood cells (12% vs. 5%), lymphocyte counts (28% vs. 19%), and neutrophil counts (13% vs. 6%). Most infections and hematologic abnormalities (e.g., leukopenia, neutropenia, or lymphopenia) were mild to moderate in severity. Monitor patients during treatment for signs and symptoms of infection. If a serious infection occurs, institute appropriate therapy and consider withholding treatment until the infection resolves. Delay treatment in patients with an active infection until the infection resolves.
Headache, including migraine and procedural headache, occurred in 32% of patients who received efgartigimod alfa 10 mg/kg (n = 84) compared to 29% of patients who received placebo (n = 83) during a clinical study in patients with generalized myasthenia gravis. Paresthesias, including oral hypoesthesia, hypoesthesia, and hyperesthesia, occurred in 7% of patients who received efgartigimod alfa 10 mg/kg compared to 5% of patients who received placebo. On average, patients received 2 cycles of efgartigimod alfa, with mean and median times to the second treatment cycle of 94 and 72 days from the initial infusion of the first treatment cycle.
Myalgia occurred in 6% of patients who received efgartigimod alfa 10 mg/kg (n = 84) compared to 1% of patients who received placebo (n = 83) during a clinical study in patients with generalized myasthenia gravis. On average, patients received 2 cycles of efgartigimod alfa, with mean and median times to the second treatment cycle of 94 and 72 days from the initial infusion of the first treatment cycle.
Hypersensitivity reactions, including anaphylactoid reactions (anaphylaxis) and hypotension leading to syncope, were observed during postmarketing experience with efgartigimod alfa. Anaphylaxis and hypotension occurred during the infusion or within 1 hour of drug administration. Temporary and permanent treatment discontinuation was reported. Additional hypersensitivity reactions, including rash, angioedema, and dyspnea, were observed in patients who received efgartigimod alfa during clinical studies. Hypersensitivity reactions occurred within 1 hour to 3 weeks of administration, were mild to moderate, and did not lead to treatment discontinuation. Monitor patients during the infusion and for 1 hour after the infusion for signs and symptoms of hypersensitivity reactions. If a hypersensitivity reaction occurs, institute appropriate supportive measures, if needed. Efgartigimod alfa is associated with a variety of infusion-related reactions, including hypertension, chills, shivering, thoracic pain, abdominal pain, and back pain. Consider the risks and benefits of efgartigimod alfa therapy in patients with a previous history of a severe infusion-related reaction to the drug. Patients who experience mild to moderate infusion-related reactions may be rechallenged with close clinical monitoring, slower infusion rates, and premedications. If a severe infusion-related reaction occurs during administration, institute appropriate therapy and discontinue efgartigimod alfa.
As with all therapeutic proteins, there is the potential for immunogenicity and antibody formation with efgartigimod alfa use. In a clinical study of efgartigimod alfa of up to 26 weeks of treatment, 20% patients (n = 83) developed antibodies to efgartigimod alfa. Neutralizing antibodies to efgartigimod alfa developed in 7% patients. Data are too limited to make definitive conclusions about the impact of antibody development on efgartigimod alfa efficacy, safety, or pharmacokinetics.
Efgartigimod alfa may increase the risk of infection. Monitor patients during treatment for signs and symptoms of infection. If a serious infection occurs, institute appropriate therapy and consider withholding treatment until the infection resolves. Delay treatment in patients with an active infection until the infection resolves. Higher incidences of respiratory tract and urinary tract infections occurred in patients treated with efgartigimod alfa compared to patients treated with placebo in clinical studies. Efgartigimod alfa treatment was associated with lower white blood cell concentrations, lymphocyte counts, and neutrophil counts compared to placebo treatment during clinical studies; periodic monitoring of complete blood counts (CBC) may be advisable for some patients, such as those with immunosuppression. Vaccination with live or live-attenuated vaccines is not recommended during treatment with efgartigimod alfa. The safety of live vaccine immunization and the response to immunization during treatment is unknown. Administer necessary age-appropriate vaccines according to immunization guidelines before initiation of a treatment cycle of efgartigimod alfa.
Efgartigimod alfa is contraindicated for use in patients with a history of serious hypersensitivity to efgartigimod alfa or any excipient in the formulation. Hypersensitivity reactions, including anaphylaxis and hypotension leading to syncope, were observed during postmarketing experience with efgartigimod alfa. Monitor patients during administration and for 1 hour after the infusion for clinical signs and symptoms of hypersensitivity reactions. If a hypersensitivity reaction occurs, institute appropriate supportive measures, if needed. Efgartigimod alfa is associated with a variety of infusion-related reactions, including hypertension, chills, shivering, and thoracic, abdominal, and back pain. Consider the risks and benefits of efgartigimod therapy in patients with a previous history of a severe infusion-related reaction to the drug. Patients who experience mild to moderate infusion-related reactions may be rechallenged with close clinical monitoring, slower infusion rates, and premedications. If a severe infusion-related reaction occurs during administration, institute appropriate therapy and discontinue efgartigimod alfa.
There are no adequate data regarding the developmental risk associated with efgartigimod alfa use during human pregnancy. Efgartigimod alfa may be transmitted from the mother to the fetus. Monoclonal antibodies are transported across the placenta as pregnancy progresses, with the greatest transfer occurring in the third trimester. There was no evidence of adverse developmental outcomes following the administration of efgartigimod alfa at doses up to 10 times the recommended human dose (RHD) of 10 mg/kg in animal studies. There may be considerations at birth for exposed neonates. A reduction in passive protection in the newborn is expected since efgartigimod alfa reduces maternal IgG levels. Consider the benefits and risks of live or live-attenuated vaccine administration to neonates with in utero exposure to efgartigimod alfa.
There are no data regarding the presence of efgartigimod alfa in human milk, the effects on the breastfed infant, or the effects on milk production. Maternal IgG is present in human milk. Consider the developmental and health benefits of breast-feeding along with the clinical need for efgartigimod alfa and any potential adverse effects on the breastfed infant from efgartigimod alfa or the underlying maternal condition.
For the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive:
NOTE: The FDA has designated efgartigimod alfa as an orphan drug for this indication.
Intravenous dosage:
Adults weighing less than 120 kg: 10 mg/kg IV infusion once weekly for 4 weeks. Administer subsequent treatment cycles based on clinical evaluation. The safety of initiating subsequent cycles sooner than 50 days from the start of the previous treatment cycle has not been established. MISSED DOSES: Administer the dose up to 3 days after the missed dose and resume the original dosage schedule until the treatment cycle is complete.
Adults weighing 120 kg or more: 1,200 mg IV infusion once weekly for 4 weeks. 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. MISSED DOSES: Administer the dose up to 3 days after the missed dose and resume the original dosage schedule until the treatment cycle is complete.
Maximum Dosage Limits:
-Adults
Weight less than 120 kg: 10 mg/kg once weekly IV for 4 weeks.
Weight 120 kg or more: 1,200 mg once weekly IV for 4 weeks.
-Geriatric
Weight less than 120 kg: 10 mg/kg once weekly IV for 4 weeks.
Weight 120 kg or more: 1,200 mg once weekly IV for 4 weeks.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
No dosage adjustments are needed.
Patients with Renal Impairment Dosing
Mild renal impairment (eGFR 60 mL/minute/1.73 m2 or more): No dosage adjustments are needed.
Moderate (eGFR 30 to 59 mL/minute/1.73 m2) and severe renal impairment (eGFR less than 30 mL/minute/1.73 m2): Specific guidelines for dosage adjustments are not available due to insufficient data.
*non-FDA-approved indication
Bacillus Calmette-Guerin Vaccine, BCG: (Major) Avoid the use of live vaccines and live attenuated vaccines during efgartigimod treatment. Live vaccinations may be less effective during efgartigimod treatment and may carry the risk of infection. Administer indicated vaccines prior to initiating efgartigimod.
Chikungunya Vaccine, Live: (Major) Avoid the use of live vaccines and live attenuated vaccines during efgartigimod treatment. Live vaccinations may be less effective during efgartigimod treatment and may carry the risk of infection. Administer indicated vaccines prior to initiating efgartigimod.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the dengue virus vaccine. When feasible, administer indicated vaccines at least 2 weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Eculizumab: (Major) Avoid coadministration of efgartigimod and eculizumab. Both medications provide targeted treatment in patients with generalized myasthenia gravis who are anti-acetylcholine receptor antibody positive. Duplicate treatment may increase the risks of immunosuppression and infection.
Hyaluronidase, Recombinant; Immune Globulin: (Moderate) Monitor for reduced efficacy of immune globulin during coadministration with efgartigimod. Concomitant use of efgartigimod with medications that bind to the human neonatal Fc receptor (FcRn), such as immune globulin, may reduce immune globulin exposure and efficacy. Consider efgartigimod discontinuation and the use of alternative therapies if long-term therapy with immune globulin is needed.
Immune Globulin IV, IVIG, IGIV: (Moderate) Monitor for reduced efficacy of immune globulin during coadministration with efgartigimod. Concomitant use of efgartigimod with medications that bind to the human neonatal Fc receptor (FcRn), such as immune globulin, may reduce immune globulin exposure and efficacy. Consider efgartigimod discontinuation and the use of alternative therapies if long-term therapy with immune globulin is needed.
Intranasal Influenza Vaccine: (Major) Avoid the use of live vaccines and live attenuated vaccines during efgartigimod treatment. Live vaccinations may be less effective during efgartigimod treatment and may carry the risk of infection. Administer indicated vaccines prior to initiating efgartigimod.
Live Vaccines: (Major) Avoid the use of live vaccines and live attenuated vaccines during efgartigimod treatment. Live vaccinations may be less effective during efgartigimod treatment and may carry the risk of infection. Administer indicated vaccines prior to initiating efgartigimod.
Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Major) Avoid the use of live vaccines and live attenuated vaccines during efgartigimod treatment. Live vaccinations may be less effective during efgartigimod treatment and may carry the risk of infection. Administer indicated vaccines prior to initiating efgartigimod.
Measles/Mumps/Rubella Vaccines, MMR: (Major) Avoid the use of live vaccines and live attenuated vaccines during efgartigimod treatment. Live vaccinations may be less effective during efgartigimod treatment and may carry the risk of infection. Administer indicated vaccines prior to initiating efgartigimod.
Ravulizumab: (Moderate) Monitor for reduced efficacy of ravulizumab during coadministration with efgartigimod. Concomitant use of ravulizumab with human neonatal Fc receptor (FcRn) blockers, such as efgartigimod, may reduce ravulizumab exposure and efficacy.
Rotavirus Vaccine: (Major) Avoid the use of live vaccines and live attenuated vaccines during efgartigimod treatment. Live vaccinations may be less effective during efgartigimod treatment and may carry the risk of infection. Administer indicated vaccines prior to initiating efgartigimod.
Rozanolixizumab: (Moderate) Monitor for a decrease in efgartigimod efficacy during concomitant use of efgartigimod and rozanolixizumab. Concomitant use of efgartigimod with medications that bind to the human neonatal Fc receptor (FcRn), such as rozanolixizumab, may decrease efgartigimod exposure. Consider rozanolixizumab discontinuation and the use of alternative therapies if long-term therapy with efgartigimod is needed.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Smallpox and Monkeypox Vaccine, Live, Nonreplicating: (Major) Avoid the use of live vaccines and live attenuated vaccines during efgartigimod treatment. Live vaccinations may be less effective during efgartigimod treatment and may carry the risk of infection. Administer indicated vaccines prior to initiating efgartigimod.
Smallpox Vaccine, Vaccinia Vaccine: (Major) Avoid the use of live vaccines and live attenuated vaccines during efgartigimod treatment. Live vaccinations may be less effective during efgartigimod treatment and may carry the risk of infection. Administer indicated vaccines prior to initiating efgartigimod.
Typhoid Vaccine: (Major) Avoid the use of live vaccines and live attenuated vaccines during efgartigimod treatment. Live vaccinations may be less effective during efgartigimod treatment and may carry the risk of infection. Administer indicated vaccines prior to initiating efgartigimod.
Varicella-Zoster Virus Vaccine, Live: (Major) Avoid the use of live vaccines and live attenuated vaccines during efgartigimod treatment. Live vaccinations may be less effective during efgartigimod treatment and may carry the risk of infection. Administer indicated vaccines prior to initiating efgartigimod.
Yellow Fever Vaccine, Live: (Major) Avoid the use of live vaccines and live attenuated vaccines during efgartigimod treatment. Live vaccinations may be less effective during efgartigimod treatment and may carry the risk of infection. Administer indicated vaccines prior to initiating efgartigimod.
Efgartigimod alfa is a human immunoglobulin G1 (IgG1) antibody fragment that binds to the neonatal Fc receptor (FcRn), resulting in the reduction of circulating IgG, including the abnormal antiacetylcholine receptor (AChR) antibodies that are present in patients with generalized myasthenia gravis (gMG). In patients with myasthenia gravis who test positive for the AChR antibody, the AChR antibodies interfere with communication between nerves and muscles, resulting in weakness.
Efgartigimod alfa is administered intravenously. It has a volume of distribution of 15 to 20 L. Efgartigimod alfa is degraded by enzymatic proteolysis into small peptides and amino acids. Less than 0.1% of a dose was recovered in urine of healthy subjects after a single IV dose of 10 mg/kg. The terminal half-life of efgartigimod alfa is 80 to 120 hours.
Affected cytochrome P450 isoenzymes and drug transporters: None
Efgartigimod alfa is not metabolized by cytochrome P450 enzymes. Interactions with CYP450 enzyme substrates, inducers, or inhibitors are not expected.
-Route-Specific Pharmacokinetics
Intravenous Route
Efgartigimod alfa exhibits linear pharmacokinetics after intravenous administration. Efgartigimod exposure increases proportionally with doses up to 50 mg/kg (5 times the recommended dosage).
-Special Populations
Hepatic Impairment
The pharmacokinetics of efgartigimod alfa in patients with hepatic impairment have not been studied. Hepatic impairment is not expected to affect the pharmacokinetics of efgartigimod alfa.
Renal Impairment
Patients with mild renal impairment (eGRF 60 to 89 mL/minute/1.72 m2) had a 22% increase in efgartigimod alfa exposure compared to patients with normal renal function in a population pharmacokinetic analysis of data from clinical studies; however, no dosage adjustment is recommended. Data are not available for patients with moderate or severe renal impairment (eGFR 59 mL/minute/1.73 m2 or less). Dedicated pharmacokinetic studies of efgartigimod alfa in patients with renal impairment have not been performed.
Geriatric
A population pharmacokinetic analysis did not suggest any clinically significant impact of age on efgartigimod alfa exposures.
Gender Differences
A population pharmacokinetic analysis did not suggest any clinically significant impact of gender on efgartigimod alfa exposures.
Ethnic Differences
A population pharmacokinetic analysis did not suggest any clinically significant impact of race on efgartigimod alfa exposures.