efgartigimod/hyaluronidase SC

Action and Spectrum

Actions and Spectrum: 

efgartigimod and hyaluronidase SC are different medications with distinct mechanisms of action and spectrum of activity. 

efgartigimod: efgartigimod is a monoclonal antibody designed to treat certain autoimmune disorders, specifically targeting the neonatal Fc receptor (FcRn). The FcRn is responsible for rescuing immunoglobulin G (IgG) antibodies from degradation, thereby extending their half-life in the body. By binding to the FcRn, efgartigimod blocks the interaction between IgG antibodies and the FcRn, leading to the accelerated degradation of pathogenic IgG antibodies. 

Spectrum of activity: efgartigimod is primarily used for the treatment of autoimmune disorders, including: 

• Myasthenia gravis: A neuromuscular disorder characterized by muscle weakness and fatigue. 
• Chronic inflammatory demyelinating polyneuropathy (CIDP): A neurological disorder causing progressive weakness and impaired limb sensation. 
• Primary immune thrombocytopenia (ITP): A condition characterized by low platelet counts, leading to an increased risk of bleeding. 
• Multifocal motor neuropathy (MMN): A rare immune-mediated motor neuropathy causing muscle weakness and atrophy. 

hyaluronidase SC: hyaluronidase is an enzyme that degrades hyaluronic acid, a significant component of the extracellular matrix. It is combined with subcutaneous (SC) injections to increase the dispersion and absorption of other injected drugs. 

Mechanism of action: hyaluronidase breaks down hyaluronic acid, a gel-like substance forming a barrier within the extracellular matrix. By degrading hyaluronic acid, hyaluronidase increases tissue permeability and facilitates the dispersion and absorption of co-administered medications, such as local anesthetics or subcutaneously administered fluids. 

Spectrum of activity: hyaluronidase is primarily used as an adjuvant to enhance the absorption and dispersion of injected drugs.  

• Subcutaneous fluid administration: hyaluronidase can be added to subcutaneously administered fluids to increase their absorption rate. 
• Local anesthesia: When injected alongside local anesthetics, hyaluronidase helps to spread the anesthetic agent through tissues, improving its effectiveness and onset of action. 
• Contrast media for diagnostic imaging: hyaluronidase can be combined with radiographic contrast agents to enhance their diffusion and distribution, improving diagnostic imaging quality. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Respiratory tract infection (33%) 

Headache (32%) 

Injection site reactions (38%) 

1-10% 

Paresthesia (7%) 

Myalgia (6%) 

Urinary tract infection (10%) 

Black Box Warning

Black box warning: 

None 

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

None 

Caution: 

• Infusion-related reactions: efgartigimod may cause infusion-related reactions, including hypersensitivity reactions. 
• Infections: efgartigimod may increase the risk of infections. Before initiating treatment, it is crucial to evaluate patients for underlying infections and consider therapy’s potential risks and benefits. 
• Vaccinations: Live or live-attenuated vaccines should be avoided during treatment with efgartigimod due to the potential for reduced efficacy.  
• Autoantibody interference: efgartigimod may interfere with specific laboratory tests that rely on measuring IgG antibodies, leading to inaccurate results. This interference can persist for up to 6 months after the last dose. 
• Allergic reactions: hyaluronidase may cause allergic reactions, including local and systemic hypersensitivity reactions.  
• Local tissue damage: Improper injection technique or excessive doses of hyaluronidase may result in local tissue damage, including necrosis.

Pregnancy / Lactation

Pregnancy consideration: Insufficient data available 

Lactation: Excretion of the drug in human breast milk is unknown 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

• efgartigimod is a recombinant human immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that selectively binds to the neonatal Fc receptor (FcRn). FcRn is responsible for rescuing IgG antibodies from degradation, extending their half-life in the body. By binding to FcRn, efgartigimod competitively inhibits the binding of IgG antibodies to FcRn, leading to increased degradation and clearance of IgG antibodies. This reduction in IgG antibody levels helps modulate the immune response and attenuate autoimmune diseases. 
• hyaluronidase is an enzyme that degrades hyaluronic acid, a naturally occurring polysaccharide present in the extracellular matrix. By enzymatically breaking down hyaluronic acid, hyaluronidase increases tissue permeability and facilitates the dispersion and absorption of co-administered medications. It helps enhance the spread and diffusion of injected drugs, fluids, or local anesthetics into the surrounding tissues. 

Pharmacokinetics: 

Absorption 

efgartigimod alfa exhibits dose-proportional absorption when administered subcutaneously. Exposures increase proportionally with increasing doses. 

Distribution 

The volume of distribution (Vd) of efgartigimod is estimated to be between 15-20 liters.  

Metabolism 

efgartigimod is expected to undergo degradation by proteolytic enzymes into small peptides and amino acids. This metabolic pathway is consistent with the breakdown of endogenous immunoglobulins. 

Elimination and Excretion 

efgartigimod has a long elimination half-life of 80-120 hours (3-5 days). The majority of efgartigimod is likely eliminated through intracellular degradation and clearance. efgartigimod is minimally excreted in the urine, with less than 0.1% of a single dose being recovered unchanged in the urine. 

Adminstartion

Administration: 

efgartigimod is administered intravenously (IV) as an infusion. The specific administration instructions may vary depending on the product and the treated condition.  

hyaluronidase is administered subcutaneously (SC) to enhance the absorption and dispersion of co-administered drugs. It is available as a solution or lyophilized powder for reconstitution. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: efgartigimod/hyaluronidase SC 

Why do we use efgartigimod/hyaluronidase SC? 

efgartigimod and hyaluronidase SC have different uses and are indicated for therapeutic purposes. Here are the common uses of efgartigimod and hyaluronidase SC: 

efgartigimod: efgartigimod primarily treats certain autoimmune disorders, specifically those associated with excessive production of disease-causing immunoglobulin G (IgG) antibodies. It is indicated for the following conditions: 

• Generalized Myasthenia Gravis (gMG): efgartigimod is approved for treating adult patients with gMG who have anti-acetylcholine receptor (AChR) antibody positivity. 
• Chronic Inflammatory Demyelinating Polyneuropathy (CIDP): efgartigimod is indicated for treating adult patients with CIDP. 

efgartigimod reduces the levels of pathogenic IgG antibodies, which play a role in developing and progressing these autoimmune disorders. 

hyaluronidase SC: hyaluronidase is an enzyme that enhances the dispersion and absorption of co-administered drugs when administered subcutaneously. It is commonly used with other medications or fluids to facilitate subcutaneous delivery. Some of the potential uses of hyaluronidase SC include: 

• Facilitation of Subcutaneous Fluid Administration: hyaluronidase can increase the absorption and dispersion of subcutaneously administered fluids, such as hydration solutions or contrast agents. 
• Facilitation of Subcutaneous Drug Administration: hyaluronidase may enhance the absorption and dispersion of subcutaneously administered medications, allowing for improved drug delivery and therapeutic effects.