ATC Group: J06BD Antiviral monoclonal antibodies

Infection with pathogenic filoviruses, such as Zaire ebolavirus (Ebola virus, EBOV), can cause severe hemorrhagic fever in humans, resulting in frequent outbreaks with case fatality rates as high as 90%.[A225933, A225938] Virtually all steps of the EBOV lifecycle have been targeted for therapeutic development. However, to date, the most successful method appears to be the development of monoclonal antibodies (mAbs) against the GP_1,2 surface glycoprotein, as evidenced by the previously approved INMAZEB™ (REGN-EB3, a cocktail of [atoltivimab], [odesivimab], and [maftivimab]), the now approved ansuvimab, and ZMapp, which remains in clinical trials.[A225933] Ansuvimab, formerly mAb114, is a fully human IgG1 mAb derived from a survivor of the 1995 Kikwit EBOV outbreak 11 years after infection, which displays strong glycan-independent binding to a conserved region of the GP_1,2 protein that is responsible for interacting with the host NPC1 protein to mediate EBOV endolysosomal escape, a key step in the EBOV lifecycle.[A225943, A225948, A226035] A randomized, controlled trial of four investigational therapies for Ebola virus disease (EVD) in the Democratic Republic of Congo during a previous outbreak that began in 2018 compared ansuvimab, REGN-EB3, ZMapp, and [remdesivir], a nucleoside analogue designed to inhibit viral replication, showed ansuvimab and REGN-EB3 to be superior, with improved patient survival and faster viral clearance rates.[A207646]

Ansuvimab received FDA approval on December 21, 2020, and is currently marketed as Ebanga by Ridgeback Biotherapeutics, LP. Ansuvimab is just the second FDA-approved treatment for EVD.[L29560]

Casirivimab (IgG1κ) and imdevimab (IgG1λ) are two recombinant human monoclonal antibodies which are unmodified in the Fc regions. Casirivimab and imdevimab bind to non-overlapping epitopes of the spike protein receptor binding domain (RBD) of SARS-CoV-2. This prevents RBD binding to the human ACE2 receptor, so preventing virus entry into cells.

Nirsevimab is a recombinant neutralising human IgG1ĸ long-acting monoclonal antibody to the prefusion conformation of the RSV F protein which has been modified with a triple amino acid substitution (YTE) in the Fc region to extend serum half-life. Nirsevimab inhibits the essential membrane fusion step in the viral entry process, neutralising the virus and blocking cell-to-cell fusion.

Palivizumab is a humanised IgG1κ monoclonal antibody directed to an epitope in the A antigenic site of the fusion protein of respiratory syncytial virus (RSV). This humanised monoclonal antibody is composed of human (95%) and murine (5%) antibody sequences. It has potent neutralising and fusion-inhibitory activity against both RSV subtype A and B strains.

Regdanvimab is a recombinant human IgG1 monoclonal antibody that binds to the receptor binding domain (RBD) of the spike(s) protein of SARS-CoV-2 consequently blocking cellular entry and SARS-CoV-2 infection.

Sotrovimab is a dual action, engineered human IgG1 mAb that binds to a conserved epitope on the spike protein receptor binding domain of SARS-CoV-2. It is used for the treatment of symptomatic adults and adolescents with acute covid-19 infection who do not require oxygen supplementation and who are at increased risk of progressing to severe covid infection.

Tixagevimab and cilgavimab are two recombinant human IgG1 monoclonal antibodies, with amino acid substitutions in the Fc regions, to extend antibody half-life and to reduce antibody effector function and potential risk of antibody-dependent enhancement of disease. Tixagevimab and cilgavimab can simultaneously bind to non-overlapping regions of the spike protein receptor binding domain (RBD) of SARS-CoV-2. Tixagevimab, cilgavimab and their combination bind to spike blocking its interaction with the human ACE2 receptor, resulting in a blockade of virus entry.