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| Primary information |
|---|
| ID | 15963 |
| Therapeutic ID | Th1656 |
| Protein Name | Maftivimab |
| Sequence | >Th1656_Maftivimab
EVQLVESGGGLVQPGGSLRLSCAASGFTSSSYAMNWVRQAPGKGLEWVSTISGMGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKRGYPHSFDIWGQGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
|
| 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 | Treatments for Ebola Virus Disease |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Envelope glycoprotein |
| Brand Name | NA |
| Company | NA |
| Brand Description | NA |
| Prescribed For | NA |
| Chemical Name | NA |
| Formulation | NA |
| Physical Appearance | NA |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |