ZMapp
An experimental combination of three humanized monoclonal antibodies targeted at three Orthoebolavirus zairense glycoprotein epitopes, engineered for expression in tobacco plants.[179]Bishop BM. Potential and emerging treatment options for Ebola virus disease. Ann Pharmacother. 2015 Feb;49(2):196-206.
http://www.ncbi.nlm.nih.gov/pubmed/25414384?tool=bestpractice.com
[180]Goodman JL. Studying "secret serums": toward safe, effective Ebola treatments. N Engl J Med. 2014 Sep 18;371(12):1086-9.
https://www.nejm.org/doi/full/10.1056/NEJMp1409817
http://www.ncbi.nlm.nih.gov/pubmed/25140857?tool=bestpractice.com
[181]Zhang Y, Li D, Jin X, et al. Fighting Ebola with ZMapp: spotlight on plant-made antibody. Sci China Life Sci. 2014 Oct;57(10):987-8.
http://www.ncbi.nlm.nih.gov/pubmed/25218825?tool=bestpractice.com
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.[182]Qiu X, Wong G, Audet J, et al. Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp. Nature. 2014 Oct 2;514(7520):47-53.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4214273
http://www.ncbi.nlm.nih.gov/pubmed/25171469?tool=bestpractice.com
The PALM trial found that ZMapp was inferior to both atoltivimab/maftivimab/odesivimab and ansuvimab at reducing mortality.[168]Mulangu S, Dodd LE, Davey RT Jr, et al. A randomized, controlled trial of Ebola virus disease therapeutics. N Engl J Med. 2019 Dec 12;381(24):2293-303.
https://www.doi.org/10.1056/NEJMoa1910993
http://www.ncbi.nlm.nih.gov/pubmed/31774950?tool=bestpractice.com
The World Health Organization (WHO) suggests against treatment with ZMapp as the evidence is very uncertain regarding any true benefits or harms.[167]World Health Organization. Therapeutics for Ebola virus disease - Democratic Republic of the Congo. Aug 2022 [internet publication].
https://www.who.int/publications/i/item/9789240055742
Remdesivir
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.[160]Warren T, Jordan R, Lo M, et al. Nucleotide prodrug GS-5734 is a broad-spectrum Filovirus inhibitor that provides complete therapeutic protection against the development of Ebola Virus Disease (EVD) in infected non-human primates. Late breaker abstract 2. Presented at IDWeek. San Diego, 2015.
https://idsa.confex.com/idsa/2015/webprogram/Paper54208.html
The PALM trial found that remdesivir was inferior to atoltivimab/maftivimab/odesivimab, ansuvimab, and ZMapp at reducing mortality.[168]Mulangu S, Dodd LE, Davey RT Jr, et al. A randomized, controlled trial of Ebola virus disease therapeutics. N Engl J Med. 2019 Dec 12;381(24):2293-303.
https://www.doi.org/10.1056/NEJMoa1910993
http://www.ncbi.nlm.nih.gov/pubmed/31774950?tool=bestpractice.com
The WHO suggests against treatment with remdesivir as the effects on mortality and serious adverse events remains very uncertain.[167]World Health Organization. Therapeutics for Ebola virus disease - Democratic Republic of the Congo. Aug 2022 [internet publication].
https://www.who.int/publications/i/item/9789240055742
Remdesivir is now being used for the treatment of coronavirus disease 2019 (COVID-19).
Favipiravir
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 orthoebolaviruses in mouse models.[183]Furuta Y, Takahashi K, Shiraki K, et al. T-705 (favipiravir) and related compounds: novel broad-spectrum inhibitors of RNA viral infections. Antiviral Res. 2009 Jun;82(3):95-102.
http://www.ncbi.nlm.nih.gov/pubmed/19428599?tool=bestpractice.com
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.[184]Sissoko D, Laouenan C, Folkesson E, et al. Experimental treatment with favipiravir for Ebola virus disease (the JIKI trial): a historically controlled, single-arm proof-of-concept trial in Guinea. PLoS Med. 2016 Mar 1;13(3):e1001967.
https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1001967
http://www.ncbi.nlm.nih.gov/pubmed/26930627?tool=bestpractice.com