Avigan
Favipiravir, also known as T-705, Avigan, or ‘’’Favipira’’’, or favilavir is an antiviral drug being developed by Toyama Chemical (Fujifilm group) of Japan with activity against many RNA viruses. Like certain other experimental antiviral drugs (T-1105 and T-1106), it is a pyrazinecarboxamide derivative. In experiments conducted in animals Favipiravir has shown activity against influenza viruses, West Nile virus, yellow fever virus, foot-and-mouth disease virus as well as other flaviviruses, arenaviruses, bunyaviruses and alphaviruses.[1] Activity against enteroviruses[2] and Rift Valley fever virus has also been demonstrated.[3] Favipiravir has showed limited efficacy against Zika virus in animal studies, but was less effective than other antivirals such as MK-608.[4] The agent has also shown some efficacy against rabies,[5] and has been used experimentally in some humans infected with the virus
Mechanism of action
The mechanism of its actions is thought to be related to the selective inhibition of viral RNA-dependent RNA polymerase.[7] Other research suggests that favipiravir induces lethal RNA transversion mutations, producing a nonviable viral phenotype.[8] Favipiravir is a prodrug that is metabolized to its active form, favipiravir-ribofuranosyl-5'-triphosphate (favipiravir-RTP), available in both oral and intravenous formulations.[9][10] Human hypoxanthine guanine phosphoribosyltransferase (HGPRT) is believed to play a key role in this activation process.[11] Favipiravir does not inhibit RNA or DNA synthesis in mammalian cells and is not toxic to them.[1] In 2014, favipiravir was approved in Japan for stockpiling against influenza pandemics.[12] However, favipiravir has not been shown to be effective in primary human airway cells, casting doubt on its efficacy in influenza treatment.[13]
Approval status
In 2014, Japan approved Favipiravir for treating viral strains unresponsive to current antivirals.[14] Toyama Chemical initially hoped that Favipiravir would become a new influenza drug that could replace Tamiflu. However, animal experiments show the potential for teratogenic effects on fetuses, and the approval of production by The Ministry of Health, Labor and Welfare was greatly delayed and the production condition is limited only in an emergency in Japan.[15]
In March 2015, the US Food and Drug Administration completed a Phase III clinical trial studying the safety and efficacy of Favipiravir in the treatment of influenza.[16]
On 15 March 2020 the drug was approved in China with the name Favilavir for the treatment of influenza.[17] The drug was also approved for use in clinical trials for treating coronavirus disease 2019 pneumonia.[17]
On 22 March 2020 Italy has approved the drug for experimental use against COVID-19 and has begun conducting trials in 3 regions most affected by the disease.[18] The Italian Pharmaceutical Agency, however, has reminded the public that the existing evidence in support of this drug is scant and preliminary.[19]
Ebola virus trials
Some research has been done suggesting that in mouse models Favipiravir may have efficacy against Ebola. Its efficacy against Ebola in humans is unproven.[20][21][22] During the 2014 West Africa Ebola virus outbreak, it was reported that a French nurse who contracted Ebola while volunteering for MSF in Liberia recovered after receiving a course of favipiravir.[23] A clinical trial investigating the use of favipiravir against Ebola virus disease was started in Guéckédou, Guinea, during December 2014.[24] Preliminary results showed a decrease in mortality rate in patients with low-to-moderate levels of Ebola virus in the blood, but no effect on patients with high levels of the virus, a group at a higher risk of death.[25] The trial design has been criticised by Scott Hammer and others for using only historical controls.[26] The results of this clinical trial were presented in February 2016 at the annual Conference on Retroviruses and Opportunistic Infections (CROI) by Daouda Sissoko[27] and published on 1 March 2016 in PLOS Medicine
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