Ansuvimab

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%. 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 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. 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 protein that is responsible for interacting with the host NPC1 protein to mediate EBOV endolysosomal escape, a key step in the EBOV lifecycle. 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.

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.

Ansuvimab is indicated for the treatment of Zaire ebolavirus infection in adult and pediatric patients, including neonates born to a mother who tests positive for Zaire ebolavirus by RT-PCR.

Ansuvimab has not been shown to be effective against other species within the Ebolavirus and Marburgvirus genera; factors such as the possible emergence of resistant strains suggest local information on circulating Zaire ebolavirus strains should be consulted before initiating treatment.