Atoltivimab/maftivimab/odesivimab (formerly known as REGN-EB3) is an antibody cocktail consisting of three fully human monoclonal antibodies targeted at three nonoverlapping Zaire ebolavirus glycoprotein epitopes. The three antibodies bind to the glycoprotein on the surface of the virus simultaneously and block the attachment and entry of the virus. It is the first treatment to be approved by the Food and Drug Administration (FDA) for the treatment of Zaire ebolavirus infection, and is approved for use in children and adults. Atoltivimab/maftivimab/odesivimab was evaluated in the PALM trial, a multi-center, open-label, randomized controlled trial, as well as part of an expanded access program conducted in the Democratic Republic of the Congo (DRC) during the 2018 outbreak. The primary efficacy endpoint in the trial was 28-day mortality. Of the patients who received atoltivimab/maftivimab/odesivimab, 33.5% died after 28 days compared to 51% of patients in the control group (ZMapp). Atoltivimab/maftivimab/odesivimab is administered as a single intravenous dose. Adverse effects include infusion-related reactions, fever/chills, tachycardia, tachypnea, hypotension, hypoxia, and elevated hepatic enzymes. The antibody combination has also received orphan drug designation from the European Medicines Agency.
Ansuvimab (formerly known as mAb114) is a human IgG1 monoclonal antibody targeted to the Zaire ebolavirus glycoprotein. It was isolated from a human survivor of the 1995 outbreak in Kikwit (Democratic Republic of the Congo), and developed by the National Institutes of Health in the US. The PALM trial found that ansuvimab was superior to ZMapp at reducing mortality. Of the patients who received ansuvimab, 35.1% died after 28 days compared to 51% of patients in the control group (ZMapp). Ansuvimab is administered as a single intravenous dose. It has been granted breakthrough therapy designation by the FDA, and is currently undergoing priority review.
An experimental combination of three humanized monoclonal antibodies targeted at three Ebola virus glycoprotein epitopes, engineered for expression in tobacco plants. ZMapp was found to be protective when administered to nonhuman primates 24-48 hours after infection. Another study showed that the drug was able to rescue nonhuman primates when treatment is initiated up to 5 days after infection. The PALM trial found that ZMapp was inferior to both atoltivimab/maftivimab/odesivimab and ansuvimab at reducing mortality.
A prodrug of adenine nucleotide analog that has potent activity against a variety of filoviruses in primate cell infection models. Initial studies have demonstrated excellent effectiveness as a treatment in nonhuman primates infected with Ebola virus. The PALM trial found that remdesivir was inferior to atoltivimab/maftivimab/odesivimab, ansuvimab, and ZMapp at reducing mortality. It is now being used for the treatment of coronavirus disease 2019 (COVID-19).
Formerly known as T-705, favipiravir is an experimental antiviral drug that selectively inhibits viral RNA-dependent RNA polymerase. It is active against influenza viruses, West Nile virus, yellow fever virus, foot-and-mouth disease virus, as well as other flaviviruses, arenaviruses, bunyaviruses, and alphaviruses. The drug is currently approved in Japan for influenza pandemics, but has been found to be effective against Ebola virus in mouse models. Human phase II trials in Guinea used a higher dose than that used for influenza. The JIKI trial, a multicenter nonrandomized trial undertaken in Guinea in 2014-2015, suggested good tolerability at a higher dose in a low-resource setting, as well as a potential benefit in patients with low viral loads.
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