NAV

Odesivimab

Identification

总结

Odesivimabis part of a product containing three monoclonal IgG1κ antibodies directed against the GP1,2 glycoprotein of Zaire ebolavirus. Together, these three antibodies act to neutralize viral particles and to recruit immune effectors for the destruction of both viral particles and infected cells.

Brand Names
Inmazeb
Generic Name
Odesivimab
DrugBank一ccession Number
DB15900
Background

Ebola virus (EBOV) remains an important human pathogen within theEbolavirusgenus, having been responsible for at least 17 known outbreaks with an average case fatality rate of 43.92%.1Immune therapy using monoclonal antibodies (mAbs) is becoming an increasingly attractive therapeutic method to combat infectious diseases due to its rapid development, low toxicity, and high specificity.3The chief surface target of EBOV particles is the GP1,2glycoprotein, which also appears on the surface of EBOV-infected cells, offering opportunities for both neutralizing and cytotoxic (i.e. through Fc-mediated immune effector function) antibody effects to play a role in combatting EBOV infection.1,2A recent large-scale study elucidated that both neutralizing and Fc-mediated functions of antibodies were important for therapeutic benefit in animal models of EBOV infection.3

INMAZEB™, formerly referred to as REGN-EB3, combines the three humanized IgG1κ mAbs Odesivimab (REGN 3471),Maftivimab(REGN 3479), andAtoltivimab(REGN 3470) in equimolar proportions. All three mAbs bind to a distinct portion of the GP1,2glycoprotein and collectively provide neutralizing and Fc-mediated immune effector function against EBOVin vitroand protection against EBOV infectionin vivo. INMAZEB™ is produced by Regeneron Pharmaceuticals and was granted FDA approval on October 14, 2020.4

Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Chemical Formula
C6506H10024N1720O2030S42
蛋白质平均体重
146164.54 Da (Polypeptide only)
Sequences
Not Available
Synonyms
  • Odesivimab
  • odesivimab-ebgn
External IDs
  • REGN-3471
  • REGN3471
  • WHO 11033

Pharmacology

Indication

Odesivimab is indicated in combination withMaftivimabandAtoltivimabfor the treatment ofZaire ebolavirusinfection in adult and pediatric patients, including neonates born to a mother who has been confirmed positive by RT-PCR forZaire ebolavirusinfection. This combination has not been established as efficacious for any other species within either theEbolavirusorMarburgvirusgenera; special care should be taken to evaluate the susceptibility of circulatingZaire ebolavirusstrains before beginning treatment, and the possible emergence of resistance should be monitored.4

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Associated Conditions
Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug events
Improve clinical decision support with information oncontraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events & improve clinical decision support.
Learn more
Pharmacodynamics

Odesivimab is a fully-humanized IgG1κ monoclonal antibody (mAb) directed against the GP1,2glycoprotein that provides both neutralizing and Fc-dependent immune-mediated activity againstZaire ebolavirus. As a mAb, Odesivimab exhibits low toxicity and is generally well tolerated but does include the risk of potentially life-threatening hypersensitivity reactions.4

Mechanism of action

Ebola virus (EBOV) is one of several viruses within theEbolavirusgenus known to infect humans with an average case fatality rate of 43.92%.1EBOV particles expose the GP1,2glycoprotein on their surface, which comprises a trimer of GP1and GP2subunit heterodimers, with the subunits connected by a disulfide bond. GP1,2plays an important role in both cell surface attachment/entry and eventual lysosomal escape through binding to the NPC intracellular cholesterol transporter 1/Niemann-Pick C1 protein (NPC1). In this manner, GP1,2is integral to the pathogenic cycle of EBOV.1,2

Odesivimab is a fully-humanized IgG1κ monoclonal antibody (mAb) directed against the EBOV GP1,2glycoprotein, which binds within the "chalice" structure near the GP head in partial contact with the glycan cap with a binding affinity (KD) of between 8.26 and 8.42 nM.2,4Odesivimab exhibits weak (<50%) neutralization of chimeric lentiviral particles expressing EBOV GP1,2and is able to bind soluble GP1,2. In addition, Odesivimab is capable of dose-dependent activation of FcγRIIIa signalling in effector cells in the presence of GP1,2-expressing cells with a half-maximal effective concentration (EC50) of 1.6 nM.2Combined withMaftivimabandAtoltivimab, Odesivimab works to block EBOV cell infection and lysosomal escape, as well as the potential antibody-dependent cell-mediated killing of EBOV-infected cells.1,2,3,4

Target Actions Organism
AEnvelope glycoprotein
antagonist
 Zaire ebolavirus (strain Mayinga-76)
Absorption

Odesivimab administered to healthy subjects at 50 mg/kg produced a mean Cmaxof 1260 ± 81.2 mg/L and a mean AUC0-∞of 25,600 ± 5040 mg*day/L.4

Volume of distribution

Odesivimab administered to healthy subjects at 50 mg/kg produced a mean steady-state volume of distribution of 56.0 ± 3.16 mL/kg.4

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

Odesivimab administered to healthy subjects at 50 mg/kg has a mean elimination half-life of 25.3 ± 3.86 days.4

Clearance

Odesivimab administered to healthy subjects at 50 mg/kg has a mean clearance of 2.02 ± 0.374 mL/day/kg.4

Adverse Effects
Improve decision support & research outcomes
With structured adverse effects data, including:blackbox warnings, adverse reactions, warning & precautions, & incidence rates.
Learn more
Improve decision support & research outcomes with our structured adverse effects data.
Learn more
Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRsBrowse all" title="" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug InteractionsLearn More" title="" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
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 software
Abciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Odesivimab.
Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Odesivimab.
Adenovirus type 7 vaccine live The therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Odesivimab.
Aducanumab The risk or severity of adverse effects can be increased when Aducanumab is combined with Odesivimab.
Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Odesivimab.
Alirocumab The risk or severity of adverse effects can be increased when Alirocumab is combined with Odesivimab.
Amivantamab The risk or severity of adverse effects can be increased when Odesivimab is combined with Amivantamab.
Anifrolumab The risk or severity of adverse effects can be increased when Anifrolumab is combined with Odesivimab.
Ansuvimab The risk or severity of adverse effects can be increased when Odesivimab is combined with Ansuvimab.
炭疽人类免疫球蛋白 The risk or severity of adverse effects can be increased when Anthrax immune globulin human is combined with Odesivimab.
Identify potential medication risks
Easily compare up to 40 drugs with our drug interaction checker.
Get severity rating, description, and management advice.
Learn more
Food Interactions
No interactions found.

产品

Drug product information from 10+ global regions
Our datasets provide approved product information including:
做sage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Mixture Products
Name 成分 Dosage Route Labeller Marketing Start Marketing End Region Image
Inmazeb Odesivimab(241.7 mg/14.5mL)+Atoltivimab(241.7 mg/14.5mL)+Maftivimab(241.7 mg/14.5mL) Injection, solution Intravenous Regeneron Pharmaceuticals, Inc. 2020-10-14 Not applicable US flag
Inmazeb Odesivimab(483.3 mg/14.5mL)+Atoltivimab(483.3 mg/14.5mL)+Maftivimab(483.3 mg/14.5mL) Injection, solution Intravenous Regeneron Pharmaceuticals, Inc. 2021-07-29 Not applicable US flag

Categories

Drug Categories
Chemical TaxonomyProvided byClassyfire
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
  • Zaire ebolavirus (strain Mayinga-76)

Chemical Identifiers

UNII
UY9LQ8P6HW
CAS number
2135632-30-1

References

Synthesis Reference

Pascal KE, Dudgeon D, Trefry JC, Anantpadma M, Sakurai Y, Murin CD, Turner HL, Fairhurst J, Torres M, Rafique A, Yan Y, Badithe A, Yu K, Potocky T, Bixler SL, Chance TB, Pratt WD, Rossi FD, Shamblin JD, Wollen SE, Zelko JM, Carrion R Jr, Worwa G, Staples HM, Burakov D, Babb R, Chen G, Martin J, Huang TT, Erlandson K, Willis MS, Armstrong K, Dreier TM, Ward AB, Davey RA, Pitt MLM, Lipsich L, Mason P, Olson W, Stahl N, Kyratsous CA: Development of Clinical-Stage Human Monoclonal Antibodies That Treat Advanced Ebola Virus Disease in Nonhuman Primates. J Infect Dis. 2018 Nov 22;218(suppl_5):S612-S626. doi: 10.1093/infdis/jiy285.
通用再保险公司ferences
  1. Jacob ST, Crozier I, Fischer WA 2nd, Hewlett A, Kraft CS, Vega MA, Soka MJ, Wahl V, Griffiths A, Bollinger L, Kuhn JH: Ebola virus disease. Nat Rev Dis Primers. 2020 Feb 20;6(1):13. doi: 10.1038/s41572-020-0147-3. [Article]
  2. Pascal KE, Dudgeon D, Trefry JC, Anantpadma M, Sakurai Y, Murin CD, Turner HL, Fairhurst J, Torres M, Rafique A, Yan Y, Badithe A, Yu K, Potocky T, Bixler SL, Chance TB, Pratt WD, Rossi FD, Shamblin JD, Wollen SE, Zelko JM, Carrion R Jr, Worwa G, Staples HM, Burakov D, Babb R, Chen G, Martin J, Huang TT, Erlandson K, Willis MS, Armstrong K, Dreier TM, Ward AB, Davey RA, Pitt MLM, Lipsich L, Mason P, Olson W, Stahl N, Kyratsous CA: Development of Clinical-Stage Human Monoclonal Antibodies That Treat Advanced Ebola Virus Disease in Nonhuman Primates. J Infect Dis. 2018 Nov 22;218(suppl_5):S612-S626. doi: 10.1093/infdis/jiy285. [Article]
  3. Saphire EO, Schendel SL, Gunn BM, Milligan JC, Alter G: Antibody-mediated protection against Ebola virus. Nat Immunol. 2018 Nov;19(11):1169-1178. doi: 10.1038/s41590-018-0233-9. Epub 2018 Oct 17. [Article]
  4. FDA Approved Drug Products: INMAZEB (atoltivimab, maftivimab, and odesivimab-ebgn) injection [Link]
RxNav
2461434
Wikipedia
Odesivimab

Clinical Trials

Clinical TrialsLearn More" title="" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count
2 Not Yet Recruiting Prevention Ebolavirus Disease 1
Not Available Available Not Available Ebolavirus Disease 1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Form Route Strength
Injection, solution Intravenous
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not Available

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets tounlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Details 1.Envelope glycoprotein
Kind
Protein
Organism
Zaire ebolavirus (strain Mayinga-76)
Pharmacological action
Yes
Actions
Antagonist
Curator comments
Odesivimab is a fully-humanized IgG1κ monoclonal antibody (mAb) directed against the EBOV GP1,2glycoprotein, which binds within the "chalice" structure near the GP head in partial contact with the glycan cap with a binding affinity (KD) of between 8.26 and 8.42 nM.[A221830, L17320]
General Function
Envelope glycoprotein Trimeric GP1,2 complexes form the virion surface spikes and mediate the viral entry processes, with GP1 acting as the receptor-binding subunit and GP2 as the membrane fusion subunit. At later times of infection, downregulates the expression of various host cell surface molecules that are essential for immune surveillance and cell adhesion. Down-modulates several integrins including ITGA1, ITGA2, ITGA3, ITGA4, ITGA5, ITGA6, ITGAV and ITGB1. This decrease in cell adhesion molecules may lead to cell detachment, contributing to the disruption of blood vessel integrity and hemorrhages developed during infection (cytotoxicity). Interacts with host TLR4 and thereby stimulates the differentiation and activation of monocytes leading to bystander death of T-lymphocytes (PubMed:28542576). Downregulates as well the function of host natural killer cells (PubMed:30013549). Counteracts the antiviral effect of host BST2/tetherin that restricts release of progeny virions from infected cells. However, cooperates with VP40 and host BST2 to activate canonical NF-kappa-B pathway in a manner dependent on neddylation.
Specific Function
Identical protein binding
Gene Name
GP
Uniprot ID
Q05320
Uniprot Name
Envelope glycoprotein
分子量
74463.855 Da
References
  1. Pascal KE, Dudgeon D, Trefry JC, Anantpadma M, Sakurai Y, Murin CD, Turner HL, Fairhurst J, Torres M, Rafique A, Yan Y, Badithe A, Yu K, Potocky T, Bixler SL, Chance TB, Pratt WD, Rossi FD, Shamblin JD, Wollen SE, Zelko JM, Carrion R Jr, Worwa G, Staples HM, Burakov D, Babb R, Chen G, Martin J, Huang TT, Erlandson K, Willis MS, Armstrong K, Dreier TM, Ward AB, Davey RA, Pitt MLM, Lipsich L, Mason P, Olson W, Stahl N, Kyratsous CA: Development of Clinical-Stage Human Monoclonal Antibodies That Treat Advanced Ebola Virus Disease in Nonhuman Primates. J Infect Dis. 2018 Nov 22;218(suppl_5):S612-S626. doi: 10.1093/infdis/jiy285. [Article]
  2. FDA Approved Drug Products: INMAZEB (atoltivimab, maftivimab, and odesivimab-ebgn) injection [Link]

Drug created at October 16, 2020 15:19 / Updated at January 27, 2022 21:15