Clinical Evaluation of Ebola Virus Disease Therapeutics

Guodong Liu, Gary Wong, Shuo Su, Yuhai Bi, Frank Plummer, George F. Gao, Gary Kobinger, Xiangguo Qiu

Research output: Contribution to journalReview articlepeer-review

13 Scopus citations

Abstract

Ebola virus disease (EVD) was first described over 40 years ago, but no treatment has been approved for humans. The 2013–2016 EVD outbreak in West Africa has expedited the clinical evaluation of several candidate therapeutics that act through different mechanisms, but with mixed results. Nevertheless, these studies are important because the accumulation of clinical data and valuable experience in conducting efficacy trials under emergency circumstances will lead to better implementation of similar studies in the future. Here, we summarize the results of EVD clinical trials, focus on the discussion of factors that may have potentially impeded the effectiveness of existing candidate therapeutics, and highlight considerations that may help meet the challenges ahead in the quest to develop clinically approved drugs. EVD causes severe hemorrhagic fever in humans, with high fatality rates, with no approved drugs for treatment. Several candidate therapeutics were clinically assessed during the recent 2013–2016 outbreak in West Africa. Two small molecule inhibitors of viral replication and transcription, a nucleotide analog (favipiravir), and siRNA, did not yield a survival benefit in clinical trials, although administration of favipiravir appeared to be more beneficial for patients with lower viral loads (i.e., in the earlier stages of EVD). The survival benefit was inconclusive in clinical trials with immune-product-based therapies, including interferon, convalescent plasma, and an mAb cocktail. The data show that the mAb cocktail, ZMapp, may have the best potential for a substantial therapeutic benefit. Further clinical investigations that could be rapidly initiated early during an outbreak will help conclusively evaluate the true effectiveness of available candidate therapeutics.

Original languageEnglish (US)
Pages (from-to)820-830
Number of pages11
JournalTrends in Molecular Medicine
Volume23
Issue number9
DOIs
StatePublished - Sep 2017
Externally publishedYes

Keywords

  • convalescent plasma
  • Ebola virus
  • monoclonal antibody
  • small molecule inhibitor
  • therapeutics

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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