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
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 myasthenia gravis (MG).3 IgG antibodies, including the autoantibodies responsible for MG symptoms, can be 'recycled', a process which significantly extends their half-life, by evading lysosomal degradation via binding with FcRn.5 By antagonizing this interaction, efgartimod alfa prevents this recycling phase and thus decreases the half-life of IgG, effectively lowering circulating levels of IgG autoantibodies against AChRs.

Efgartimod alfa was granted FDA approval on December 17, 2021.4

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
References:
  1. NIH Inxight: Efgartimod alfa [Link]
Download FASTA Format
Synonyms
  • Efgartigimod alfa
External IDs
  • ARGX-113

Pharmacology

Indication

Efgartigimod alfa is indicated for the treatment of generalized myasthenia gravis in adult patients who are anti-acetylcholine receptor antibody-positive.3

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Associated Conditions
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 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

TargetActionsOrganism
AIgG receptor FcRn large subunit p51
binder
Humans
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.
DrugInteraction
Adenovirus type 7 vaccine liveThe risk or severity of adverse effects can be increased when Efgartigimod alfa is combined with Adenovirus type 7 vaccine live.
Anthrax vaccineThe risk or severity of adverse effects can be increased when Efgartigimod alfa is combined with Anthrax vaccine.
Bacillus calmette-guerin substrain connaught live antigenThe risk or severity of adverse effects can be increased when Efgartigimod alfa is combined with Bacillus calmette-guerin substrain connaught live antigen.
Bacillus calmette-guerin substrain russian BCG-I live antigenThe risk or severity of adverse effects can be increased when Efgartigimod alfa is combined with Bacillus calmette-guerin substrain russian BCG-I live antigen.
Bacillus calmette-guerin substrain tice live antigenThe risk or severity of adverse effects can be increased when Efgartigimod alfa is combined with Bacillus calmette-guerin substrain tice live antigen.
BCG vaccineThe risk or severity of adverse effects can be increased when Efgartigimod alfa is combined with BCG vaccine.
Human adenovirus e serotype 4 strain cl-68578 antigenThe risk or severity of adverse effects can be increased when Efgartigimod alfa is combined with Human adenovirus e serotype 4 strain cl-68578 antigen.
Rubella virus vaccineThe risk or severity of adverse effects can be increased when Efgartigimod alfa is combined with Rubella virus vaccine.
Typhoid Vaccine LiveThe risk or severity of adverse effects can be increased when Efgartigimod alfa is combined with Typhoid Vaccine Live.
Varicella zoster vaccine (live/attenuated)The risk or severity of adverse effects can be increased when Efgartigimod alfa is combined with Varicella zoster vaccine (live/attenuated).
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Food Interactions
No interactions found.

Products

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International/Other Brands
Vyvgart (argenx BV)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
VyvgartInjection20 mg/1mLIntravenousargenx US2021-12-17Not applicableUS flag

Categories

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
  1. Beloor Suresh A, Asuncion RMD: Myasthenia Gravis . [Article]
  2. 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]
  3. FDA Approved Drug Products: Vyvgart (efgartigimod alfa-fcab) for intravenous injection [Link]
  4. FDA News Release: FDA Approves New Treatment for Myasthenia Gravis [Link]
  5. Argenx: Efgartigimod Proposed Mechanism of Action [Link]
RxNav
2587717
Wikipedia
Efgartigimod_alfa

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentMyasthenia Gravis, Generalized1
3Active Not RecruitingTreatmentPrimary Immune Thrombocytopenia (ITP)2
3CompletedTreatmentMyasthenia Gravis, Generalized1
3CompletedTreatmentPrimary Immune Thrombocytopenia (ITP)1
3RecruitingTreatmentPrimary Immune Thrombocytopenia (ITP)1
3WithdrawnTreatmentPrimary Immune Thrombocytopenia (ITP)1
2CompletedTreatmentMyasthenia Gravis1
2CompletedTreatmentPemphigus Foliaceus / Pemphigus Vulgaris (PV)1
2CompletedTreatmentPrimary Immune Thrombocytopenia (ITP)1
2RecruitingTreatmentChronic Inflammatory Demyelinating Polyradiculoneuropathy1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
InjectionIntravenous20 mg/1mL
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not Available

Targets

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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
  1. FDA Approved Drug Products: Vyvgart (efgartigimod alfa-fcab) for intravenous injection [Link]

Drug created at May 20, 2019 15:06 / Updated at January 27, 2022 21:15