Drug Repurposing for Ebola Virus Disease: Principles of Consideration and the Animal Rule

Abstract

There are no approved drugs or biologics to treat Ebola virus disease (EVD). Literature reviews identified a list of 141 drugs with reports of preliminary in vitro potency and in vivo effectiveness in animals or with reports of clinical use/trials in EVD patients. The majority of these drugs have been individually approved by the U.S. Food and Drug Administration for treating various non-EVD diseases. The anti-Ebola potency data of these drugs were curated from literature and publicly accessible databases, along with their individual biopharmaceutical and pharmacokinetic characteristics. To facilitate the development of antiviral drugs including anti-EVD drugs, highlights include optimization of the exposure-response relationship, design of a safe and effective clinical dosing regimen to achieve an adequate high ratio of clinical C_min to a plasma protein binding-adjusted EC₉₅, and the pharmacokinetic studies needed in animal models (healthy and affected) and in healthy volunteers. The exposure/response relationship for human dose selection is summarized, as described in the U.S. Food and Drug Administration "Animal Rule'' guidance when human efficacy studies are not ethical or feasible.

Keywords: anti-infective(s); bioavailability; clinical pharmacokinetics; dose-response; global health; regulatory science.