The following article is intended for Prescribers only
In 2019, the World Health Organization (WHO) listed a potential global influenza pandemic amongst one of the ten most significant threats to global health.[1] Since the emergence of COVID-19, is influenza still a potential pandemic threat, and what role might Favipiravir play?
Antivirals are considered by WHO as an important adjunct to vaccination for reducing the medical and economic burden of seasonal influenza pandemics.[2] Favipiravir is a broad-spectrum antiviral that selectively inhibits viral RNA-dependent RNA polymerase, the enzyme responsible for building the proteins in wide range of viruses, including influenza.[3]
FAVIPIRAVIR AS AN ANTI-INFLUENZA COMPOUND
Favipiravir was first characterized as an anti-influenza compound in 2002.4 In vitro and in vivo studies subsequently demonstrated Favipiravir to have better efficacy in treating influenza infections than oseltamivir an influenza-specific neuraminidase inhibitor currently recommended by WHO for treating influenza infections.[2]
After the completion of Phase III clinical trials,[3] in 2014 Favipiravir was approved as a treatment for novel or re-emerging influenza viruses in Japan.[7] The following year, the Taiwanese Centers for Disease Control (CDC) decided to stockpile Favipiravir for people who became infected with new strains of influenza, including avian and swine influenzas.[7] Additionally, the Japanese government decided to stockpile AVIGAN®/Favipiravir as a novel influenza countermeasure for 2 million people in 2017.[7]
INFLUENZA IN THE CONTEXT OF COVID-19
For almost two years, the entire world has focused on the continuously evolving COVID-19 pandemic. While cases of COVID-19 have steadily risen over time, during the first year of the pandemic influenza infection rates saw a sharp decline. This was most likely due to COVID-19 restrictions preventing influenza from spreading through communities. Between September 2020 and the end of January 2021, the US Centers for Disease Control and Prevention (CDC) had logged just 1,316 positive flu cases in its surveillance network. Compare that to the previous season (pre-COVID-19) when the CDC recorded nearly 130,000 cases of influenza.[8]
HOW MUCH OF A THREAT IS AN INFLUENZA PANDEMIC?
Back in 2019, WHO believed that the world would eventually face another influenza pandemic – what is unknown is when it will hit and how severe it will be.[1] Amidst the background of the current COVID-19 pandemic, WHO continues to monitor the circulation of influenza viruses to detect potential pandemic strains throughout the world.
On January 2nd 2022, one of the first ever cases of ‘flurona’ – a co-infection of both SARS-CoV-2 and influenza virus – was recorded at Beilinson Hospital in Petah Tikva, Israel.[9] The two infections were detected in an unvaccinated pregnant woman who fortunately had only mild symptoms. An investigation into whether a combination of the two viruses can cause more severe illness is ongoing.[9] At time of writing such cases of dual infection have yet to rise significantly.
On January 24th 2022, WHO stated that, “Globally, influenza activity remained low and appeared to decrease.”[10] However, WHO also acknowledged that in some countries, influenza activity had reached the levels seen this time of year during the pre-COVID-19 period.[10] It is not yet clear how this variation in infection rates relates to local COVID-19 restrictions.
Considering this uncertainty, to promote worldwide influenza pandemic preparedness WHO is now recommending that governments prepare for the co-circulation of influenza and SARS-CoV-2, and for clinicians to consider influenza in differential diagnosis especially for high-risk groups.[10]
FAVIPIRAVIR AND THE POTENTIAL INFLUENZA PANDEMIC
One of the unique features of AVIGAN® and QIFENDA™ (Favipiravir) is its broad-spectrum activity toward RNA viruses, including both influenza viruses (A & B) and SARS-CoV-2.[11] In June 2019, Favipiravir was approved in India by the Indian Drug Regulator under accelerated approval process for the treatment of mild-to-moderate COVID-19 under restricted emergency use.[12] Since then, Favipiravir has shown much promise in helping to reduce the health impact of COVID-19.[13][14]
Time will tell as to when the next influenza pandemic will arise, and indeed how it may compound the impact that COVID-19 is having on global healthcare systems. However, as the only orally administered antiviral agent that has dual efficacy against influenza A & B and SARS-CoV-2 viruses, Favipiravir is well positioned as an effective weapon in the fight against not only the COVID-19 pandemic, but also the next influenza pandemic, when it happens.
BACKGROUND & SUMMARY
AVIGAN® and QIFENDA™:
Favipiravir is a broad-spectrum oral antiviral originally developed by FUJIFILM Toyama Chemicals in 2014 as a medical countermeasure for pandemic influenza. One of the advantages of AVIGAN® / QIFENDA™ is that it fights COVID-19 at home and significantly reduces the likelihood of patients progressing to hospital - which significantly reduces pressures on healthcare systems. AVIGAN® / QIFENDA™ is at the most advanced stage of pharmaceutical product life cycle of any COVID-19 treatment available globally. There are now more than 1.5 million patients worldwide that have been administered AVIGAN® which already puts AVIGAN® on the front line in the fight against COVID-19 and future pandemic preparedness.
References
1. World Health Organization – Ten threats to global health in 2019. (2019). https://www.who.int/news-room/spotlight/ten-threats-to-global-health-in-2019 (Accessed 4 February 2022).
2. World Health Organization. Seasonal influenza – About antivirals. (2022). https://www.euro.who.int/en/health-topics/communicable-diseases/influenza/seasonal-influenza/clinical-management/about-antiviral-drugs (Accessed 4 February 2022).
3. Shannon A et al. Rapid incorporation of Favipiravir by the fast and permissive viral RNA polymerase complex results in SARS-CoV-2 lethal mutagenesis. Nat Commun 2020; 11(1): 4682. doi: 10.1038/s41467-020-18463-z.
4. Furuta Y et al. In vitro and in vivo activities of anti-influenza virus compound T-705. Antimicrob Agents Chemother 2002; 46: 977–981.
5. Takahashi K et al. In vitro and in vivo activities of T-705 and oseltamivir against influenza virus. Antivir Chem Chemother 2003; 14: 235–241.
6. Tanaka T et al. T-705 (Favipiravir) suppresses tumor necrosis factor alpha production in response to influenza virus infection: A beneficial feature of T-705 as an anti-influenza drug. Acta Virologica 2017; 61: 48–55.
7. Shiraki K & Daikoku T. Favipiravir, an anti-influenza drug against life-threatening RNA virus infections. Pharmacol Ther 2020; 209: 107512. doi: 10.1016/j.pharmthera.2020.107512.
8. Harvard T.H. Chan. A sharp drop in flu cases during COVID-19 pandemic. (2021). https://www.hsph.harvard.edu/news/hsph-in-the-news/a-sharp-drop-in-flu-cases-during-covid-19-pandemic/ (Accessed 4 February 2022).
9. The Times of Israel. ‘Flurona’: Israel records its first case of patient with COVID and flu at same time. (2022). https://www.timesofisrael.com/flurona-israel-records-its-first-case-of-patient-with-covid-and-flu-at-same-time/ (Accessed 4 February 2022).
10. World Health Organization. Global Influenza Programme – Influenza Update Number 410. (2022). https://www.who.int/teams/global-influenza-programme/surveillance-and-monitoring/influenza-updates/current-influenza-update (Accessed 4 February 2022).
11. Furuta Y et al. Favipiravir (T-705), a broad-spectrum inhibitor of viral RNA polymerase. Proc Jpn Acad Ser B Phys Biol Sci 2017; 93(7): 449–463.
12. Joshi S et al. Role of favipiravir in the treatment of COVID-19. Int J Infect Dis 2021;102:501–508.
13. Ucan A et al. Benefits of treatment with favipiravir in hospitalized patients for COVID-19: a retrospective observational case–control study. Virol J 2021;18(1):102. doi: 10.1186/s12985-021-01577-1.
14. Abdelnabi R et al. The combined treatment of Molnupiravir and Favipiravir results in a potentiation of antiviral efficacy in a SARS-CoV-2 hamster infection model. EBioMedicine 2021 Oct;72:103595. doi: 10.1016/j.ebiom.2021.103595. Epub 2021 Sep 24.