Efgartigimod alfa
Identification
- Summary
Efgartigimod alfa is a neonatal Fc receptor blocker used to treat generalized myasthenia gravis in patients who are AChR-antibody positive.
- Brand Names
- Vyvgart, Vyvgart Hytrulo
- Generic Name
- Efgartigimod alfa
- DrugBank Accession Number
- DB15270
- Background
Myasthenia gravis (MG) is an autoimmune disorder characterized by significant muscle weakness - particularly in the eye, throat, and extremities - caused by autoantibodies attacking the neuromuscular junction.1 The production of IgG autoantibodies against acetylcholine receptors (AChRs) is one of the more common pathophysiological mechanisms behind MG, and results in the destruction of these receptors and a reduction in electrical nerve impulses.1,2
Efgartigimod alfa is a first-in-class4 antagonist of the neonatal Fc receptor (FcRn) used in the treatment of MG.3 IgG antibodies, including the autoantibodies responsible for MG symptoms, can be 'recycled', a process that significantly extends their half-life by evading lysosomal degradation via binding with FcRn.5 By antagonizing this interaction, efgartigimod alfa prevents this recycling phase and thus decreases the half-life of IgG, effectively lowering circulating levels of IgG autoantibodies against AChRs.
Efgartigimod alfa for intravenous use was granted FDA approval on December 17, 20214 and European Commission approval on August 11, 2022.7 A formulation for subcutaneous use that combines efgartigimod alfa and hyaluronidase was approved by the FDA in June 2023.8,9
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Other protein based therapies - Protein Chemical Formula
- Not Available
- Protein Average Weight
- 54000.0 Da
- Sequences
>SUBUNIT_1 DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVD GVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK GQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDS DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALKFHYTQKSLSLSPGK
>SUBUNIT_2 DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVD GVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK GQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDS DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALKFHYTQKSLSLSPGK
Download FASTA FormatReferences:
- NIH Inxight: Efgartimod alfa [Link]
- Synonyms
- Efgartigimod alfa
- External IDs
- ARGX-113
Pharmacology
- Indication
Efgartigimod alfa - delivered intravenously as a monotherapy or subcutaneously in combination with recombinant human hyaluronidase - is indicated for the treatment of generalized myasthenia gravis in adult patients who are anti-acetylcholine receptor antibody-positive.3,6,10
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Myasthenia gravis, generalized •••••••••••• ••••• •••••••••••••••••• •••••••• •••••••• •••••••• ••••••••• Used in combination to treat Myasthenia gravis, generalized Combination Product in combination with: Hyaluronidase (human recombinant) (DB06205) •••••••••••• ••••• •••••••••••••••••• •••••••• •••••••• •••••••• ••••••••• - Contraindications & Blackbox Warnings
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- Pharmacodynamics
Efgartigimod alfa exerts its pharmacologic effect by reducing circulating levels of the autoantibody responsible for myasthenia gravis symptoms. It is administered as a once-weekly intravenous or subcutaneous infusion, given for 4 weeks per treatment cycle, with the option to initiate additional treatment cycles as clinically indicated after at least 50 days have passed following the previous cycle.3
Because efgartigimod alfa reduces circulating IgG levels, patients undergoing therapy may be at greater risk of infection due to a depressed immune response.3 It should not be initiated in patients with an active infection, and consideration should be given to holding therapy in patients who develop a serious infection during a treatment cycle.
- Mechanism of action
Myasthenia gravis (MG) is an autoimmune disorder affecting the neuromuscular junction of the skeletal muscles.1 While the pathophysiologic mechanisms of MG differ depending on the subtype in question, all forms involve the production of IgG autoantibodies to some endogenous protein. One of the most commonly implicated proteins against which autoantibodies are produced are acetylcholine receptors (AChRs), which undergo degradation via the membrane attack complex (MAC) secondary to their interaction with AChR-specific autoantibodies.1 The destruction of AChRs prevents regular transmission of electrical impulses across the neuromuscular junction, which ultimately leads to the characteristic muscular weakness - especially of the eyes, throat, and extremities - observed in patients with MG.
Immunoglobulin G, as opposed to other immunoglobulins, undergoes a recycling phase in the vascular endothelium that dramatically extends its half-life.5 In the case of pathogenic IgGs causing MG, this may facilitate an increased ability to impair neuromuscular transmission. This recycling involves IgG binding to the neonatal Fc receptor (FcRn), which rescues IgG from lysosomal degradation.5
Efgartigimod alfa is a human IgG1 antibody fragment that binds to FcRn, thus preventing IgG recycling and subsequently reducing the amount of circulating IgG, including the autoantibodies responsible for MG.3,5
Target Actions Organism AIgG receptor FcRn large subunit p51 binderHumans - Absorption
Not Available
- Volume of distribution
The volume of distribution of efgartigimod alfa ranges from 15 to 20 liters.3
- Protein binding
Not Available
- Metabolism
As with other therapeutic proteins, efgartigimod alfa is likely metabolized to smaller peptides and amino acids via proteolytic enzymes.3
- Route of elimination
After a single intravenous dose of efgartigimod alfa 10 mg/kg in healthy subjects, less than 0.1% of the administered dose was recovered in the urine.3
- Half-life
The terminal elimination half-life of efgartigimod alfa ranges from 80 to 120 hours.3
- Clearance
Not Available
- Adverse Effects
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- Toxicity
There are no data regarding overdosage with efgartigimod alfa.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbatacept The risk or severity of adverse effects can be increased when Abatacept is combined with Efgartigimod alfa. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Efgartigimod alfa. Adenovirus type 7 vaccine live The risk or severity of adverse effects can be increased when Efgartigimod alfa is combined with Adenovirus type 7 vaccine live. Aldesleukin The risk or severity of adverse effects can be increased when Aldesleukin is combined with Efgartigimod alfa. Alefacept The risk or severity of adverse effects can be increased when Alefacept is combined with Efgartigimod alfa. - Food Interactions
- No interactions found.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- International/Other Brands
- Vyvgart (argenx BV)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Vyvgart Solution 20 mg / mL Intravenous Argenx Bv 2023-11-06 Not applicable Canada Vyvgart Injection, solution 1000 mg Subcutaneous Argenx 2023-11-28 Not applicable EU Vyvgart Injection 20 mg/1mL Intravenous argenx US 2021-12-17 Not applicable US Vyvgart Injection, solution, concentrate 20 mg/ml Intravenous Argenx 2022-09-13 Not applicable EU - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image VYVGART Hytrulo Efgartigimod alfa (180 mg/1mL) + Hyaluronidase (human recombinant) (2000 U/1mL) Injection, solution Subcutaneous argenx US 2023-06-20 Not applicable US
Categories
- ATC Codes
- L04AA58 — Efgartigimod alfa
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 961YV2O515
- CAS number
- 1821402-21-4
References
- General References
- Beloor Suresh A, Asuncion RMD: Myasthenia Gravis . [Article]
- Lascano AM, Lalive PH: Update in immunosuppressive therapy of myasthenia gravis. Autoimmun Rev. 2021 Jan;20(1):102712. doi: 10.1016/j.autrev.2020.102712. Epub 2020 Nov 13. [Article]
- FDA Approved Drug Products: Vyvgart (efgartigimod alfa-fcab) for intravenous injection [Link]
- FDA News Release: FDA Approves New Treatment for Myasthenia Gravis [Link]
- Argenx: Efgartigimod Proposed Mechanism of Action [Link]
- EMA Approved Drug Products: Vyvgart (efgartigimod alfa) Intravenous Infusion [Link]
- argenx News: argenx Announces European Commission Approval of VYVGART™ (efgartigimod alfa-fcab) for the Treatment of Generalized Myasthenia Gravis [Link]
- FDA Approved Drug Products: VYVGART HYTRULO (efgartigimod alfa and hyaluronidase-qvfc) injection for subcutaneous use (June 2023) [Link]
- Globe News Wire: argenx Announces U.S. Food and Drug Administration Approval of VYVGART Hytrulo (efgartigimod alfa and hyaluronidase-qvfc) Injection for Subcutaneous Use in Generalized Myasthenia Gravis [Link]
- FDA Approved Drug Products: Vyvgart Hytrulo (efgartigimod alfa and hyaluronidase-qvfc) injection for subcutaneous administration (December 2023) [Link]
- FDA Approved Drug Products: Vyvgart (efgartigimod alfa-fcab) injection for intravenous administration (December 2023) [Link]
- External Links
- 2587717
- Wikipedia
- Efgartigimod_alfa
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Active Not Recruiting Treatment Primary Immune Thrombocytopenia (ITP) 2 3 Completed Treatment Generalized Myasthenia Gravis 2 3 Completed Treatment Primary Immune Thrombocytopenia (ITP) 2 3 Withdrawn Treatment Primary Immune Thrombocytopenia (ITP) 1 2 Active Not Recruiting Treatment Chronic Inflammatory Demyelinating Polyradiculoneuropathy 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection Intravenous 20 mg/1mL Injection, solution Subcutaneous 1000 mg Injection, solution, concentrate Intravenous 20 mg/ml Solution Intravenous 20 mg / mL Injection, solution Subcutaneous - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Binder
- General Function
- Cell surface receptor that transfers passive humoral immunity from the mother to the newborn. Binds to the Fc region of monomeric immunoglobulin gamma and mediates its selective uptake from milk (PubMed:7964511, PubMed:10933786). IgG in the milk is bound at the apical surface of the intestinal epithelium. The resultant FcRn-IgG complexes are transcytosed across the intestinal epithelium and IgG is released from FcRn into blood or tissue fluids. Throughout life, contributes to effective humoral immunity by recycling IgG and extending its half-life in the circulation. Mechanistically, monomeric IgG binding to FcRn in acidic endosomes of endothelial and hematopoietic cells recycles IgG to the cell surface where it is released into the circulation (PubMed:10998088). In addition of IgG, regulates homeostasis of the other most abundant circulating protein albumin/ALB (PubMed:24469444, PubMed:28330995).
- Specific Function
- Beta-2-microglobulin binding
- Gene Name
- FCGRT
- Uniprot ID
- P55899
- Uniprot Name
- IgG receptor FcRn large subunit p51
- Molecular Weight
- 39742.99 Da
References
- FDA Approved Drug Products: Vyvgart (efgartigimod alfa-fcab) for intravenous injection [Link]
Drug created at May 20, 2019 15:06 / Updated at January 25, 2024 05:59