Efficacy of favipiravir (T-705) in nonhuman primates infected with Ebola virus or Marburg virus

• Published in: Antiviral research 2018-03, Vol.151, p.97-104
• Main Authors: Bixler, Sandra L., Bocan, Thomas M., Wells, Jay, Wetzel, Kelly S., Van Tongeren, Sean A., Dong, Lian, Garza, Nicole L., Donnelly, Ginger, Cazares, Lisa H., Nuss, Jonathan, Soloveva, Veronica, Koistinen, Keith A., Welch, Lisa, Epstein, Carol, Liang, Li-Fang, Giesing, Dennis, Lenk, Robert, Bavari, Sina, Warren, Travis K.
• Format: Article
• Language: English
• Subjects: Ebola; Favipiravir; Marburg; Nonhuman primates; T-705; Therapeutic
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2017.12.021

Favipiravir is a broad-spectrum antiviral agent that has demonstrated efficacy against Ebola virus (EBOV) in rodents. However, there are no published reports of favipiravir efficacy for filovirus infection of nonhuman primates (NHPs). Here we evaluated the pharmacokinetic profile of favipiravir in NHPs, as well as in vivo efficacy against two filoviruses, EBOV and Marburg virus (MARV). While no survival benefit was observed in two studies employing once- or twice-daily oral dosing of favipiravir during EBOV infection of NHPs, an antiviral effect was observed in terms of extended time-to-death and reduced levels of viral RNA. However, oral dosing in biosafety level-4 (BSL-4) presents logistical and technical challenges, and repeated anesthesia events may potentially worsen survival outcome in animals. For the third study of treatment of MARV infection, we therefore made use of catheters, jackets, and tethers for intravenous (IV) dosing and blood collection, which minimized the requirement for repeated anesthesia events. When MARV infection was treated with IV favipiravir, five of six animals (83%) survived infection, while all untreated NHPs succumbed. An accompanying report presents the results of favipiravir treatment of EBOV infection in mice. •During the course of the West African Ebola epidemic, we evaluated the activity of favipiravir in nonhuman primates.•Once-daily or twice-daily oral dosing with favipiravir did not lead to improved survival following EBOV infection.•An antiviral effect against EBOV was observed in terms of increased time-to-death and reduction in viral RNA levels.•In both EBOV studies, plasma favipiravir levels exceeded the EBOV EC50.•Twice-daily intravenous dosing resulted in 83% survival following MARV infection, while all untreated animals died.