Development of experimental and early investigational drugs for the treatment of Ebola virus infections

Abstract

Introduction: Ebola virus (EBOV) causes severe hemorrhagic fever in humans, and due to the aggressive nature of infection it has been difficult to develop effective medical countermeasures. Total casualties from past outbreaks numbered fewer than 1500 cases, but EBOV unexpectedly emerged from Guinea in late 2013 and infected over 25,000 people in nine countries spanning Africa, Europe and North America. Concern among the public and authorities helped spark an unprecedented push to fast-track experimental drugs for clinical use.

Areas covered: The authors provide a historical timeline of the progress in developing a licensed post-exposure EBOV drug for use in humans. Furthermore, they summarize and discuss the published data with different in light of their potential to play a role during outbreak times.

Expert opinion: Monoclonal antibody-based therapy is able to reverse advanced EBOV disease, but the outbreak of an antigenically divergent filovirus would require the reformulation and possibly redevelopment of the most promising candidates. Immunocompetent small animal models have not yet been developed for screening drugs against other filoviruses aside from Ravn and Marburg virus, and thus the number of prophylactic and therapeutic candidates lag behind that of EBOV. There is an urgent need for the proactive development of drugs against other neglected pathogens before the next major outbreak.

Keywords:

• drugs
• Ebola
• filovirus
• nonhuman primates
• post-exposure
• therapy

Declaration of interest

This work was supported by the Public Health Agency of Canada (PHAC) and funded by a Canadian Safety and Security Program (CSSP, CP-1017) grant to X Qiu. G Wong is the recipient of a Banting Postdoctoral Fellowship from the Canadian Institutes of Health Research (CIHR). Her Majesty the Queen in right of Canada holds a patent on the mAbs 1H3, 2G4, 4G7 (PCT/CA2009/000070), ‘Monoclonal antibodies for Ebola and Marburg viruses.’ Both G Wong and X Qiu have been extensively involved in the development and testing of the mAb cocktails, as well as the VSV-vectored vaccine discussed in this review, but are not included on any related patents, other intellectual property or contracts that may benefit them financially in the future. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Notes

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