Primary information |
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ID | 15956 |
Therapeutic ID | Th1656 |
Protein Name | Maftivimab |
Sequence | >Th1656_Maftivimab
EVQLVESGGGLVQPGGSLRLSCAASGFTSSSYAMNWVRQAPGKGLEWVSTISGMGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKRGYPHSFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
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Molecular Weight | 143948.11 |
Chemical Formula | C6368H9886N1706O2008S46 |
Isoelectric Point | NA |
Hydrophobicity | NA |
Melting point | NA |
Half-life | Maftivimab administered to healthy subjects at 50 mg/kg has a mean elimination half-life of 22.3 ± 3.09 days.[L17320] |
Description | 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%.[A221825] 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.[A222078] 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.[A221825, A221830] 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.[A222078] INMAZEB™, formerly referred to as REGN-EB3, combines the three humanized IgG1 mAbs Maftivimab (REGN 3479), [Odesivimab] (REGN 3471), and [Atoltivimab] (REGN 3470) 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.[L17320] |
Indication/Disease | 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.[L17320] |
Pharmacodynamics | Maftivimab is a fully-humanized IgG1 monoclonal antibody (mAb) directed against the GP1,2 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.[L17320] |
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%.[A221825] 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.[A221825, A221830] Maftivimab is a fully-humanized IgG1 monoclonal antibody (mAb) directed against the EBOV GP1,2 glycoprotein, which binds between GP1 and GP2 protomers at the base of the GP1,2 protein with a binding affinity (_KD_) of between 2.97 and 3.34 nM.[A221830, L17320] Maftivimab exhibits strong neutralization of chimeric lentiviral particles expressing EBOV GP1,2 with a half-maximal inhibitory concentration (IC50) value or 0.17 nM, but lacks the ability to induce FcRIIIa signalling in effector cells.[A221830]. 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.[A221825, A221830, A222078, L17320] |
Toxicity | NA |
Metabolism | NA |
Absorption | Maftivimab administered to healthy subjects at 50 mg/kg produced a mean Cmax of 1280 ± 68.0 mg/L and a mean AUC0-8 of 18,700 ± 4100 mg |
| Maftivimab administered to healthy subjects at 50 mg/kg produced a mean steady-state volume of distribution of 57.6 ± 3.89 mL/kg.[L17320] |
Clearance | Maftivimab administered to healthy subjects at 50 mg/kg has a mean clearance of 2.78 ± 0.558 mL/day/kg.[L17320] |
Categories | Amino Acids, Peptides, and Proteins |
Patents Number | NA |
Date of Issue | NA |
Date of Expiry | NA |
Drug Interaction | NA |
Target | Envelope glycoprotein |
Brand Name | Inmazeb |
Company | Regeneron Pharmaceuticals, Inc. |
Brand Description | Regeneron Pharmaceuticals, Inc. |
Prescribed For | Intravenous |
Chemical Name | NA |
Formulation | None. |
Physical Appearance | fever, chills, fast heart rate, fast, shallow breathing, vomiting, low blood pressure (hypotension), diarrhea, and low blood oxygen (hypoxia) |
Route of Administration | Atoltivimab, maftivimab, and odesivimab-ebgn combination injection is used to treat infection cause by Zaire ebolavirus. This medicine is to be given only by or under the direct supervision of your doctor. Before using Inmazeb In deciding to use a medicine, the risks of taking the medicine must be weighed... |
Recommended Dosage | Inmazeb (atoltivimab, maftivimab, and odesivimab-ebgn) is a combination of Zaire ebolavirus glycoprotein-directed human monoclonal antibodies used to treat infection caused by Zaire ebolavirus in adult and pediatric patients, including neonates born to a mother who is RT-PCR positive for Zaire ebolavirus infection. |
Contraindication | NA |
Side Effects | NA |
Useful Link 1 | Link |
Useful Link 2 | Link |
Remarks | NA |