Modeling Favipiravir Antiviral Efficacy Against Emerging Viruses: From Animal Studies to Clinical Trials
Vincent Madelain, France Mentré, Sylvain Baize, Xavier Anglaret, Cédric Laouenan, Lisa Oestereich, Thi Huyen Tram Nguyen, Denis Malvy, Géraldine Piorkowski, Frederik Graw, Stephan Günther, Hervé Raoul, Xavier de Lamballerie, Jérémie Guedj
Abstract
In 2014, our research network was involved in the evaluation of favipiravir, an anti-influenza polymerase inhibitor, against Ebola virus. In this review, we discuss how mathematical modeling was used, first to propose a relevant dosing regimen in humans, and then to optimize its antiviral efficacy in a nonhuman primate (NHP) model. The data collected in NHPs were finally used to develop a model of Ebola pathogenesis integrating the interactions among the virus, the innate and adaptive immune response, and the action of favipiravir. We conclude the review of this work by discussing how these results are of relevance for future human studies in the context of Ebola virus, but also for other emerging viral diseases for which no therapeutics are available.