Maftivimab

Identification

Summary

Maftivimab is 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

Maftivimab

DrugBank Accession Number

DB15899

Background

Ebola virus (EBOV) remains an important human pathogen within the Ebolavirus genus, having been responsible for at least 17 known outbreaks with an average case fatality rate of 43.92%.¹ Immune 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.³ The chief surface target of EBOV particles is the GP_1,2 glycoprotein, 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.^1,2 A 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 Maftivimab (REGN 3479), Odesivimab (REGN 3471), and Atoltivimab (REGN 3470) in equimolar proportions. All three mAbs bind to a distinct portion of the GP_1,2 glycoprotein and collectively provide neutralizing and Fc-mediated immune effector function against EBOV in vitro and protection against EBOV infection in 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

C₆₃₆₈H₉₈₈₆N₁₇₀₆O₂₀₀₈S₄₆

Protein Average Weight

143948.11 Da (Peptide only)

Sequences

Not Available

Synonyms

• Maftivimab

External IDs

• REGN-3479
• REGN3479
• WHO 11034

Pharmacology

Indication

Maftivimab is indicated in combination with Odesivimab and Atoltivimab for the treatment of Zaire ebolavirus infection in adult and pediatric patients, including neonates born to a mother who has been confirmed positive by RT-PCR for Zaire ebolavirus infection. This combination has not been established as efficacious for any other species within either the Ebolavirus or Marburgvirus genera; special care should be taken to evaluate the susceptibility of circulating Zaire ebolavirus strains before beginning treatment, and the possible emergence of resistance should be monitored.⁴

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Associated Conditions

• Hemorrhagic Fever, Ebola

Contraindications & Blackbox Warnings

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Pharmacodynamics

Maftivimab is a fully-humanized IgG1κ monoclonal antibody (mAb) directed against the GP_1,2 glycoprotein that provides strong neutralizing activity against Zaire ebolavirus. As a mAb, maftivimab 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 the Ebolavirus genus known to infect humans with an average case fatality rate of 43.92%.¹ EBOV particles expose the GP_1,2 glycoprotein on their surface, which comprises a trimer of GP₁ and GP₂ subunit heterodimers, with the subunits connected by a disulfide bond. GP_1,2 plays 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, GP_1,2 is integral to the pathogenic cycle of EBOV.^1,2

Maftivimab is a fully-humanized IgG1κ monoclonal antibody (mAb) directed against the EBOV GP_1,2 glycoprotein, which binds between GP1 and GP2 protomers at the base of the GP_1,2 protein with a binding affinity (K_D) of between 2.97 and 3.34 nM.^2,4 Maftivimab exhibits strong neutralization of chimeric lentiviral particles expressing EBOV GP_1,2 with a half-maximal inhibitory concentration (IC₅₀) value or 0.17 nM, but lacks the ability to induce FcγRIIIa signalling in effector cells.². Combined with Odesivimab and Atoltivimab, Maftivimab 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

Maftivimab administered to healthy subjects at 50 mg/kg produced a mean C_max of 1280 ± 68.0 mg/L and a mean AUC_0-∞ of 18,700 ± 4100 mg*day/L.⁴

Volume of distribution

Maftivimab administered to healthy subjects at 50 mg/kg produced a mean steady-state volume of distribution of 57.6 ± 3.89 mL/kg.⁴

Protein binding

Not Available

Metabolism

Not Available

Route of elimination

Not Available

Half-life

Maftivimab administered to healthy subjects at 50 mg/kg has a mean elimination half-life of 22.3 ± 3.09 days.⁴

Clearance

Maftivimab administered to healthy subjects at 50 mg/kg has a mean clearance of 2.78 ± 0.558 mL/day/kg.⁴

Adverse Effects

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Toxicity

Not Available

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.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
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Abciximab	The risk or severity of adverse effects can be increased when Abciximab is combined with Maftivimab.
Adalimumab	The risk or severity of adverse effects can be increased when Adalimumab is combined with Maftivimab.
Adenovirus type 7 vaccine live	The therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Maftivimab.
Aducanumab	The risk or severity of adverse effects can be increased when Aducanumab is combined with Maftivimab.
Alemtuzumab	The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Maftivimab.
Alirocumab	The risk or severity of adverse effects can be increased when Alirocumab is combined with Maftivimab.
Amivantamab	The risk or severity of adverse effects can be increased when Maftivimab is combined with Amivantamab.
Anifrolumab	The risk or severity of adverse effects can be increased when Anifrolumab is combined with Maftivimab.
Ansuvimab	The risk or severity of adverse effects can be increased when Maftivimab is combined with Ansuvimab.
Anthrax immune globulin human	The risk or severity of adverse effects can be increased when Anthrax immune globulin human is combined with Maftivimab.

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Food Interactions

No interactions found.

Products

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Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End	Region	Image
Inmazeb	Maftivimab (483.3 mg/14.5mL) + Atoltivimab (483.3 mg/14.5mL) + Odesivimab (483.3 mg/14.5mL)	Injection, solution	Intravenous	Regeneron Pharmaceuticals, Inc.	2021-07-29	Not applicable
Inmazeb	Maftivimab (241.7 mg/14.5mL) + Atoltivimab (241.7 mg/14.5mL) + Odesivimab (241.7 mg/14.5mL)	Injection, solution	Intravenous	Regeneron Pharmaceuticals, Inc.	2020-10-14	Not applicable

Categories

Drug Categories

• Amino Acids, Peptides, and Proteins
• Anti-Infective Agents
• Antibodies
• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antiviral Agents
• Blood Proteins
• Globulins
• Immunoglobulins
• Immunoproteins
• Proteins
• Serum Globulins
• Treatments for Ebola Virus Disease

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

• Zaire ebolavirus (strain Mayinga-76)

Chemical Identifiers

UNII

KOP95331M4

CAS number

2135632-36-7

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.

General References

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]

External Links

RxNav

2461339

Wikipedia

Maftivimab

Clinical Trials

Clinical Trials

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

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Details1. Envelope glycoprotein

Kind

Protein

Organism

Zaire ebolavirus (strain Mayinga-76)

Pharmacological action

Yes

Actions

Antagonist

Curator comments

Maftivimab is a fully-humanized IgG1κ monoclonal antibody (mAb) directed against the EBOV GP_1,2 glycoprotein, which binds between GP1 and GP2 protomers at the base of the GP_1,2 protein with a binding affinity (K_D) of between 2.97 and 3.34 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

Molecular Weight

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]

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