Atoltivimab
Identification
- Summary
Atoltivimab 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
- Atoltivimab
- DrugBank Accession Number
- DB15898
- 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 GP1,2 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 Atoltivimab (REGN 3470), Odesivimab (REGN 3471), and Maftivimab (REGN 3479) in equimolar proportions. All three mAbs bind to a distinct portion of the GP1,2 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
- C6448H9954N1726O2002S44
- Protein Average Weight
- 145097.54 Da (Peptide only)
- Sequences
- Not Available
- Synonyms
- Atoltivimab
- External IDs
- REGN-3470
- REGN3470
- WHO 11032
Pharmacology
- Indication
Atoltivimab is indicated in combination with Odesivimab and Maftivimab 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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- Contraindications & Blackbox Warnings
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- Pharmacodynamics
Atoltivimab is a fully-humanized IgG1κ monoclonal antibody (mAb) directed against the GP1,2 glycoprotein that provides both neutralizing and Fc-dependent immune-mediated activity against Zaire ebolavirus. As a mAb, Atoltivimab 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 GP1,2 glycoprotein on their surface, which comprises a trimer of GP1 and GP2 subunit heterodimers, with the subunits connected by a disulfide bond. GP1,2 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, GP1,2 is integral to the pathogenic cycle of EBOV.1,2
Atoltivimab is a fully-humanized IgG1κ monoclonal antibody (mAb) directed against the EBOV GP1,2 glycoprotein, which binds the GP1,2 glycan cap parallel to the viral surface with a binding affinity (KD) of between 7.74 and 7.84 nM.2,4 Atoltivimab exhibits strong (<90%) neutralization of chimeric lentiviral particles expressing EBOV GP1,2 with a half-maximal inhibitory concentration (IC50) value of 0.27 nM. In addition, Atoltivimab 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 2.9 nM.2 Combined with Odesivimab and Maftivimab, Atoltivimab 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 antagonistZaire ebolavirus (strain Mayinga-76) - Absorption
Atoltivimab administered to healthy subjects at 50 mg/kg produced a mean Cmax of 1220 ± 101 mg/L and a mean AUC0-∞ of 17,100 ± 4480 mg*day/L.4
- Volume of distribution
Atoltivimab administered to healthy subjects at 50 mg/kg produced a mean steady-state volume of distribution of 58.2 ± 2.66 mL/kg.4
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Atoltivimab administered to healthy subjects at 50 mg/kg has a mean elimination half-life of 21.2 ± 3.36 days.4
- Clearance
Atoltivimab administered to healthy subjects at 50 mg/kg has a mean clearance of 3.08 ± 0.719 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Atoltivimab. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Atoltivimab. Adenovirus type 7 vaccine live The therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Atoltivimab. Aducanumab The risk or severity of adverse effects can be increased when Aducanumab is combined with Atoltivimab. Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Atoltivimab. Alirocumab The risk or severity of adverse effects can be increased when Alirocumab is combined with Atoltivimab. Amivantamab The risk or severity of adverse effects can be increased when Atoltivimab is combined with Amivantamab. Anifrolumab The risk or severity of adverse effects can be increased when Anifrolumab is combined with Atoltivimab. Ansuvimab The risk or severity of adverse effects can be increased when Atoltivimab 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 Atoltivimab. Identify potential medication risksEasily compare up to 40 drugs with our drug interaction checker.Get severity rating, description, and management advice.Learn more - 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.
- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Inmazeb Atoltivimab (483.3 mg/14.5mL) + Maftivimab (483.3 mg/14.5mL) + Odesivimab (483.3 mg/14.5mL) Injection, solution Intravenous Regeneron Pharmaceuticals, Inc. 2021-07-29 Not applicable US Inmazeb Atoltivimab (241.7 mg/14.5mL) + Maftivimab (241.7 mg/14.5mL) + Odesivimab (241.7 mg/14.5mL) Injection, solution Intravenous Regeneron Pharmaceuticals, Inc. 2020-10-14 Not applicable US
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
- Zaire ebolavirus (strain Mayinga-76)
Chemical Identifiers
- UNII
- FJZ07Q63VY
- CAS number
- 2135632-29-8
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
- 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]
- 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]
- 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]
- FDA Approved Drug Products: INMAZEB (atoltivimab, maftivimab, and odesivimab-ebgn) injection [Link]
- External Links
- 2461338
- Wikipedia
- Atoltivimab
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 2 Not Yet Recruiting Prevention Ebola Virus Disease 1 1 Completed Basic Science Healthy Subjects (HS) 1 Not Available Available Not Available Ebola Virus 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

- Kind
- Protein
- Organism
- Zaire ebolavirus (strain Mayinga-76)
- Pharmacological action
- Yes
- Actions
- Antagonist
- Curator comments
- Atoltivimab is a fully-humanized IgG1κ monoclonal antibody (mAb) directed against the EBOV GP1,2 glycoprotein, which binds the GP1,2 glycan cap parallel to the viral surface with a binding affinity (KD) of between 7.74 and 7.84 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
- 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]
- FDA Approved Drug Products: INMAZEB (atoltivimab, maftivimab, and odesivimab-ebgn) injection [Link]
Drug created at October 16, 2020 15:12 / Updated at February 03, 2022 19:50