Avigan® Tablets: a Broad-Spectrum Antiviral and Potential Therapeutic for COVID-19

Appili has joined a consortium of companies, including Dr. Reddy’s Laboratories LTD., Global Response Aid, and FUJIFILM Toyama Chemical Co., Ltd., for the worldwide development and distribution of Avigan tablets for the potential treatment and prevention of COVID-19

Avigan® is a broad-spectrum antiviral in oral tablet form developed by FUJIFILM Toyama Chemical Co., Ltd. (FFTC) and approved in Japan as a treatment and stockpile countermeasure for pandemic influenza. Following promising clinical studies, Russia and India recently approved favipiravir-based antiviral medications for the emergency treatment of COVID-19.  FFTC recently announced positive Phase 3 data in the use of Avigan® in hospitalized COVID-19 patients. 

 

Unlike most other interventions that researchers are evaluating in COVID-19, Avigan® has already been thoroughly studied in human trials and has a known safety profile, with over 3,000 subjects receiving at least one dose of the drug. There is also an established manufacturing process in place that can be used to ramp up supply, should the drug receive regulatory approvals in additional indications. Avigan®’s oral tablet form is shelf-stable and may provide advantages in the community setting over other COVID-19 interventions, which often require temperature-controlled storage and/or injection or intravenous administration.

“While we are encouraged by the early signals that Avigan® may be active against COVID-19, we realize that there is a duty to provide robust clinical data evaluating Avigan® as an early treatment option and prophylactic agent. Appili is honored to be a part of this world-class clinical program as we race to find options for the greatest public health threat of our lifetime.”

– Dr. Armand Balboni, CEO Appili Therapeutics

COVID-19

SARS-Cov-2, causative agent of COVID-19, is a novel coronavirus that emerged in late 2019 and rapidly spread worldwide. As of late April 2020, over three million cases had been confirmed globally, including over 50,000 in Canada and over 1,000,000 in the United States (Updated statistics are available at the Johns Hopkins Coronavirus Resource Centre). Estimates from PHAC indicate that 11,000 - 22,000 deaths and 1 million-2 million infections will likely occur in Canada before the outbreak runs its course. In Canada, most deaths resulting from COVID-19 are occurring in long-term healthcare centers, where it is particularly difficulty to stem the spread of the infection.

 

Outcomes of SARS-CoV-2 infection can vary significantly between individuals.  Some patients will experience asymptomatic infection, while others will experience symptoms typical of a respiratory infection – including fever, cough, and shortness of breath – with potential to progress to severe and potentially fatal disease requiring hospitalization and mechanical ventilation. Patients with known risk factors, such as advanced age and chronic health conditions, are more likely to experience severe illness are at greater risk of death. The problem of SARS-CoV-2 is compounded by the threat of asymptomatic transmission that undermines infection control measures, particularly in the institutional setting and in long-term care, where a large number of high-risk patients are housed in close proximity. The significant burden of COVID-19 in long-term care is increasingly recognized globally and an urgent public health challenge that must be addressed.   

 

Favipiravir

Favipiravir is a novel broad-spectrum antiviral originally developed by FFTC and is approved in Japan for stockpiling and use in an outbreak setting of pandemic influenza. Favipiravir is also active against a wide range of RNA viruses including many for which there are limited or no approved therapies. Favipiravir has been extensively studied and shown to be very well tolerated in humans at influenza dose levels, with a safety database of more than 3,000 subjects having received at least one dose of the drug. It is available in an oral dose format, stable at room temperature, and amenable to use in a wide range of care settings (Furata 2017).   

 

Early studies suggest favipiravir may have utility against COVID-19

  • Researchers at the Wuhan Institute of Virology were first to report that favipiravir was active against the novel coronavirus in cell culture (Wang 2020).

  • Two small clinical studies have also suggested potential efficacy in patients when compared to other antiviral options:

    • Patients treated with favipiravir tended to have better clinical outcomes than those treated with umifenovir, including higher clinical recovery rates, reduced time to fever reduction, and faster alleviation of cough symptoms.  The difference in clinical outcomes was most pronounced in the subset of patients with mild-to-moderate illness.

    • Favipiravir was evaluated for the treatment of COVID-19 in comparison to a lopinavir/ritonavir combination. Patients in the favipiravir group exhibited shorter time to viral clearance and showed improvements in chest imaging.

 

These early studies suggest that favipiravir has promise in treating COVID-19 patients and may have benefits over other potential approaches. However, researchers still need to assess the potential of favipiravir as a prophylactic agent.

 

With contributions of validated drug product from FFTC, Appili is sponsoring a randomized and controlled clinical trial evaluating favipiravir for COVID-19 outbreak control in long-term care settings. Appili is in ongoing negotiations with FFTC on a licensing agreement for certain rights to favipiravir.

References

Cai et al (2020) Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study. Engineering. https://doi.org/10.1016/j.eng.2020.03.007

Chen et al (2020) Favipiravir versus arbidol for COVID-19: A Randomized Clinical Trial. medRxiv preprint doi: https://doi.org/10.1101/2020.03.17.20037432

Fauci et al (2020) COVID-19: Navigating the uncharted. The New England Journal of Medicine 382: 13

Furata et al (2017) Favipiravir (T-705), a broad-spectrum inhibitor of viral RNA polymerase. Proc Jpn Acad Ser B Phys Biol Sci 93(7):449-463

Johns Hopkins Coronavirus Resource Centre: https://systems.jhu.edu/research/public-health/ncov/

Wang (2020) Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Research 30(3):269-271

Zhou et al (2020) Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet 6736(20)