Medicosnext
The pandemic outbreak of coronavirus COVID-19 that started in China in late December 2019 is a severe acute respiratory syndrome (SARS- CoV-2) and has now walloped the world. COVID-19 has led to unprecedented challenges with devastating health and socio-economic impacts. Scientists and researchers are striving to contain the coronavirus with vaccines or repurposed drugs (such as antivirals, biological drugs, vitamin supplements, and minerals). Currently, there is lack of explicit evidence on the development of herd immunity, vaccines availability, and immunity effect in long term.
Favipiravir from Fujifilm Toyama Chemical Co. Ltd., a broad spectrum novel antiviral, was initially approved and stock-piled in Japan in 2014 for new or re-emerging pandemic influenza, and has now been shown to be effective in SARS-CoV-2 in different clinical trials conducted in various countries. Favipiravir (T-705; 6-fluoro-3-hydoxy-2-pyrazinecarboxamide), selectively inhibits RNA-dependent-RNA-polymerase (RdRp) of RNA viruses, first undergoes phosphoribosylation intracellulary to be an active form: Favipiravir-RTP (Favipiravir ribofuranosyl-5’-triphosphate). Of note, Favipiravir is active against wide range of RNA virus- Arena, Bunya, Flavi, Filo, and Ebola virus, and in-vitro studies indicate no emergence of resistance.
At the outset, Favipiravir (200 mg formulation) was given approval for a clinical trial by National Medical Products Administration (NMDA) China for investigational therapy to treat coronavirus in March, 2020 based on early clinical studies that showed promising results in reduction of viral load along with improvement in clinical and radiological outcomes. Likewise, Russia issued a temporary registration certificate on June 01, 2020, announcing Avifavir as the world’s first Favipiravir-based drug to be approved for the treatment of COVID-19. Followed by India, in June 2020, Drug Controller General of India (DCGI) gave emergency approval of Favipiravir under an accelerated process for mild and moderate COVID-19 infections. An update of phase 3 clinical trial in India, sponsored by Glenmark Pharmaceuticals, was published online in November 2020 in a globally reputed peer-reviewed journal ‘The International Journal of Infectious Disease (IJID)’; significant improvement in time to clinical cure was 3 days versus 5 days, and time to cessation of viral shedding was 5 days versus 7 days for Favipiravir and control groups, respectively. A phase 3 clinical trial survey of Favipiravir for COVID-19 administered by Fujita Health University (conducted by subsidiary Fujifilm Toyama Chemical) was statistically significant and has filed for approval as of now. Till date, Favipiravir has been commercially launched in India, Bangladesh, Turkey, and most recently, in Egypt. Approval has also been granted in Saudi Arabia, UAE, and Italy for emergency use. Recently, Health Canada has provided a ‘no objection letter (NOL)’ to Canadian-based Appili Therapeutics Inc. for new phase 3 clinical trial to evaluate Favipiravir tablets in the prevention of COVID-19; the US FDA accepted submission of a protocol amendment to conduct the trial in the USA.
Around September 2020, the Department of Drug Administration (DDA) of Nepal approved Favipiravir manufactured by Nepalese-based company Deurali-Janta Pharmaceuticals Pvt. Ltd.,indicated for novel or re-emerging influenza virus infections, and as investigational use for novel coronavirus SARS-CoV-2 infection. Thereafter, Deurali-Janta, in collaboration with National Health Research Council (NHRC), begun Nepal’s first ever phase 3 clinical trial of FAVIR 200; the interim report is expected to be released soon.
Previous clinical studies have shown that antiviral drugs administered shortly after the onset of symptoms can shorten the course of clinical illness and can reduce the infectiousness to others by reducing viral shedding; this supports the ‘hit hard, hit early’ principle with antivirals. Based on known safety profile of Favipiravir from early preclinical and clinical trials, hyperuricemia and liver function abnormalities are most commonly observed adverse events. Early embryonic lethality and teratogenicity in animal models exclude Favipiravir in pregnancy, and their sexual partners should practice effective contraception during and 7 days after the end of Favipiravir treatment. Yet, being an orally administered tablet formulation, Favipiravir marks to address the majority of population with mild to moderate COVID-19 symptoms who can be treated on an outpatient basis to halt the progression of condition to severe stage.
Reference: Sources from various journal, news and articles
