Inmazeb
Inmazeb Uses, Dosage, Side Effects, Food Interaction and all others data.
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%. 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. 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. 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.
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.
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.
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%. 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. 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. 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.
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 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.
Maftivimab is a fully-humanized IgG1κ 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.
| Trade Name | Inmazeb |
| Generic | Atoltivimab + maftivimab + odesivimab-ebgn |
| Type | Intravenous |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States, |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Atoltivimab is part of a product containing three monoclonal IgG1κ antibodies directed against the GP<sub>1,2</sub> 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.
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.
Maftivimab is part of a product containing three monoclonal IgG1κ antibodies directed against the GP<sub>1,2</sub> 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.
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.
Inmazeb is also used to associated treatment for these conditions: Ebola Virus InfectionEbola Virus Infection
How Inmazeb works
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%. 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.
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. Atoltivimab exhibits strong (1,2 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. 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.
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%. 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.
Maftivimab is a fully-humanized IgG1κ 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. 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 FcγRIIIa signalling in effector cells.. 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.
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.
Maftivimab administered to healthy subjects at 50 mg/kg produced a mean steady-state volume of distribution of 57.6 ± 3.89 mL/kg.
Elimination Route
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.
Maftivimab administered to healthy subjects at 50 mg/kg produced a mean Cmax of 1280 ± 68.0 mg/L and a mean AUC0-∞ of 18,700 ± 4100 mg*day/L.
Half Life
Atoltivimab administered to healthy subjects at 50 mg/kg has a mean elimination half-life of 21.2 ± 3.36 days.
Maftivimab administered to healthy subjects at 50 mg/kg has a mean elimination half-life of 22.3 ± 3.09 days.
Clearance
Atoltivimab administered to healthy subjects at 50 mg/kg has a mean clearance of 3.08 ± 0.719 mL/day/kg.
Maftivimab administered to healthy subjects at 50 mg/kg has a mean clearance of 2.78 ± 0.558 mL/day/kg.
Innovators Monograph
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