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Favipiravir as a complement to vaccine-based strategies in treating COVID-19

Updated: Mar 28

The following article is intended for Prescribers only

Early 2020 heralded the beginnings of what would become the most significant global health crisis since the outbreak of Spanish flu 100 years ago. During those early stages of the COVID-19 pandemic, no one could have accurately predicted how it would unravel.


The eventual introduction of vaccines in late 2020 has proven undoubtedly beneficial for millions of people, and worldwide there are now more than 165 vaccine candidates, 524 ongoing vaccine trials, and 18 vaccines that are approved by at least one country.[1] However, with the uptake of vaccinations plateauing in many countries [2] and vaccine effectiveness waning against new emerging SARS-CoV-2 variants,[3][4] governments around the world have been searching for effective ways to complement vaccine-based strategies and help combat the virus.


ANTIVIRAL THERAPY


One such complementary method is antiviral therapy. First developed and approved by Japan PMDA in 2014,[5] Favipiravir is a broad-spectrum antiviral that selectively inhibits viral RNA-dependent RNA polymerase, the central component responsible for replication and transcription of viral proteins.[6] Favipiravir has potent antiviral activity against single-stranded RNA viruses including the coronavirus that causes COVID-19,[7] and is the active pharmaceutical ingredient of AVIGAN® and QIFENDA™. AVIGAN® is a 200mg Favipiravir therapeutic, whilst QIFENDA™ is a 400mg Favipiravir therapeutic. Both are the brand originator with two different dosages.


In July 2020, AVIGAN® was approved in India by the Indian Drug Regulator under an accelerated approval process for the treatment of mild-to-moderate COVID-19 under restricted emergency use.[8] Also Favipiravir has received full marketing authorization, emergency use or compassionate access authorizations in a number of countries during the past 2 years (United Arab Emirates - Morocco – Indonesia – Thailand – Malaysia - United Kingdom – Greece - Hungary - Saudi Arabia). Such emergency use authorization of Favipiravir meant that some communities were granted access to outpatient interventions in the earlier phases of the pandemic.[8] Favipiravir has since shown promise in reducing the health impact of COVID-19.[9] Clinical and pre-clinical investigations into Favipiravir’s effectiveness against COVID-19 have demonstrated that early treatment with Favipiravir may potentially help to reduce disease progression[9] and onward transmission[10] in communities.



It is now understood that currently approved vaccines can mitigate the severity of symptoms caused by variants, but they do not offer complete protection from infection and transmission. The Delta variant (B.1.617.2) is known to be 8 times more likely to evade vaccine immunity compared with the previous predominant strain,[3] and it has become the dominant variant since it was first detected in late 2020.[11] At time of writing, the Africa Health Research Institute reported that the neutralizing antibody response generated by the Pfizer/BioNTech coronavirus vaccine may be 41 times less effective against the Omicron variant (B.1.1.529) when compared against the original ancestral strain[4]—this will likely enable Omicron to surpass Delta as the dominant variant throughout the world, with even greater transmission rates.[12]


Variants of SARS-CoV-2 could therefore pose a continual strain on global healthcare systems, as we see infection rates continue to rise. As of 1st February 2022, more than 2.6 million new cases had been confirmed globally in the last 24 hours, totaling over 373 million reported infections with SARS-CoV-2, with more than 5.6 million COVID-related deaths reported.[13]


VACCINE HESITANCY


Although current vaccines appear to confer some level of protection against severity of symptoms, hospitalizations continue to rise in many populations, especially among those with relatively low vaccination rates. Concerns about unknown future effects, side effects, and a lack of trust in vaccines for COVID-19 have amplified vaccine hesitancy among some cohorts of the population,[14] leading to a reduction in vaccination uptake and ultimately having a direct or indirect impact on the global public health landscape. Importantly, the World Health Organization classified vaccine hesitancy as a direct threat to global health in 2019, prior to the outbreak of COVID.[15]


Vaccine hesitancy, the unknown length and duration of protection offered by vaccines, and their unknown efficacy against the ever-changing variants, could together derail the efforts of a vaccine-based strategy to end the current pandemic. Vaccines alone may not be enough. Therefore, a comprehensive approach utilizing public health measures, vaccination programs and importantly, complementary community-based antiviral therapies, might help to improve our chances of preventing infections from spreading.


Several antiviral drugs, including Favipiravir, are now being assessed as potential prophylactic agents for COVID-19. Encouragingly, Favipiravir has already been considered as a pharmacological post-exposure prophylaxis for Ebola virus disease.[16] AVIGAN® and QIFENDA™ therefore potentially represent effective prophylactic and presumptive treatment options for COVID-19 that may have a major impact worldwide in preventing infection as well as reducing severity of disease, especially in high-risk patients. The possibilities of AVIGAN® or QIFENDA™ on mitigating hospital admission rates and the burdens imposed upon our strained healthcare systems are also noteworthy benefits to consider.


It is crucial to remember that potential prophylactic treatments for COVID-19 should not be considered a substitute for vaccination. Nevertheless, as an orally administered complement to vaccine-based strategies AVIGAN® and QIFENDA™ may help to alleviate the significant burden of vaccine hesitancy on global healthcare services.

 

BACKGROUND & SUMMARY

AVIGAN® / QIFENDA™:

Favipiravir is a broad-spectrum oral antiviral originally developed by FUJIFILM Toyama Chemicals LTD., in 2014 as a medical countermeasure for pandemic influenza. One of the advantages of AVIGAN® 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® 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. Basta NE and Moodie EMM on behalf of the VIPER (Vaccines, Infectious disease Prevention, and Epidemiology Research) Group COVID-19 Vaccine Development and Approvals Tracker Team. COVID-19 Vaccine Development and Approvals Tracker. (2020). https://covid19.trackvaccines.org/vaccines/ (Accessed 9 December 2021).

2. European Centre for Disease Prevention and Control. Overview of the implementation of COVID-19 vaccination strategies and deployment plans in the EU/EEA. (2021). https://www.ecdc.europa.eu/en/publications-data/overview-implementation-covid-19-vaccination-strategies-and-deployment-plans (Accessed 9 December 2021).

3. Mlcochova P et al. SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion. Nature 2021;599(7883):114–119.

4. Cele S et al. (2021). SARS-CoV-2 Omicron has extensive but incomplete escape of Pfizer BNT162b2 elicited neutralization and requires ACE2 for infection. https://www.ahri.org/wp-content/uploads/2021/12/MEDRXIV-2021-267417v1-Sigal.pdf (Accessed 9 December 2021).

5. Furuta Y et al. Favipiravir (T-705), a novel viral RNA polymerase inhibitor. Antiviral Res 2013; 100(2): 446–454.

6. 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.

7. 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.

8. Joshi S et al. Role of favipiravir in the treatment of COVID-19. Int J Infect Dis 2021;102:501–508.

9. 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.

10. 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.

11. European Centre for Disease Prevention and Control. SARS-CoV-2 variants of concern as of 3 December 2021. https://www.ecdc.europa.eu/en/covid-19/variants-concern (Accessed: 9 December 2021).

12. medRxiv (2021). Omicron strain spreads with the doubling time of 3.2—3.6 days in South Africa province of Gauteng that achieved herd immunity to Delta variant. [online] www.medRvix.org. Available at: https://www.medrxiv.org/content/10.1101/2021.12.08.21267494v1.full.pdf [Accessed 1 Feb. 2022].

13. World Health Organization. (2021). WHO Coronavirus (COVID-19) Dashboard. https://covid19.who.int/ (Accessed 1 February 2022).

14. Jacobs M et al. Post-exposure prophylaxis against Ebola virus disease with experimental antiviral agents: a case-series of health-care workers. Lancet Infect Dis 2015;15(11):1300–1304.

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