Avigan (Favipiravir) Antiviral Medication Description
Avigan (T-705) Tablet was approved for manufacture and sale in Japan in 2014 as an influenza antiviral medication. Avigan should be considered for use only when there is an outbreak of novel or re-emerging influenza virus infections in which other influenza antiviral medications are either not effective or insufficiently effective, says Japan’s Health, Labor, and Welfare Ministry.
Favipiravir-based drugs are sold under various names around the world, such as Avigan, FabiFlu, Avifavir, Ciplenza, FluGuard, Avifavir, and Coronavir.
Avigan undergoes an intracellular phosphoribosylation to be an active form, favipiravir-RTP (favipiravir ribofuranosyl-5′-triphosphate), which is recognized as a substrate by RdRp, and inhibits the RNA polymerase activity. Since the catalytic domain of RdRp is conserved among various types of RNA viruses, this mechanism of action underpins a broader spectrum of anti-viral activities of favipiravir.
Avigan (favipiravir) was discovered by Toyama Chemical Co., Ltd., selectively inhibits RNA polymerase necessary for influenza virus replication. Due to this mechanism of action, it is expected that Avigan may potentially have an antiviral effect on the new coronavirus, SARS-CoV-2, because, like influenza viruses, coronaviruses are single-stranded RNA viruses that also depend on viral RNA polymerase.
On September 23, 2020, Fujifilm Toyama Chemical Co. announced a small, phase III trial in Japan, which began in March 2020, was now complete, and it intends to apply for the medication to be approved for treating coronavirus patients after trials showed it can shorten recovery time.
In this study, the median value of primary endpoints, using 156 individuals as analysis targets, were 11.9 days for the Avigan group and 14.7 days for the placebo group. FUJIFILM Toyama Chemical confirmed, with a statistically significant difference (p value = 0.0136), that the administration of Avigan to COVID-19 patients with non-serious pneumonia demonstrates shorter time to resolution. The adjusted hazard ratio*2 showed 1.593 (95% confidence interval of 1.024 – 2.479). No new safety concerns were noted in this trial.
Previously, Fujifilm signed a patent license agreement on its anti-influenza medication Avigan (favipiravir) Tablet with China's major pharmaceutical company Zhejiang Hisun Pharmaceutical during June 2016.
On June 1, 2020, Avifavir (Favipiravir) received a temporary registration certificate from the Ministry of Health of the Russian Federation, which has included Avifavir in its latest 7th edition of the guidelines for the prevention, diagnosis, and treatment of new coronavirus infection COVID-19. Starting June 10, 2020, Avifavir was delivered to more than 50 Russian regions, as well as Belarus and Kazakhstan.
Favipiravir-based drugs, such as Coronavir, have demonstrated efficacy in clinical trials held in the leading medical centers across Russia, involving patients with confirmed cases of COVID-19. The drugs disrupt the reproduction mechanisms of the coronavirus, relieving symptoms, and halving the treatment period compared to standard therapy.
Glenmark Pharmaceuticals announced on July 13, 2020, it would lower the price of its generic version of favipiravir, FabiFlu, to 75 rupees ($0.9983) per tablet. This indicates a treatment course with FabiFlu would require a patient to take 122 tablets over 14 days, and will now cost 8,475 rupees ($112.80) per patient at the new price.
And, Glenmark reported results from a phase 3 trial on July 22, 2020, that showed numerical improvements for the primary efficacy endpoint with 28.6% faster viral clearance in the overall population as measured by the median time until cessation of oral shedding of virus in the Favipiravir treatment arm. Additionally, Glenmark’s Favipiravir was well tolerated with no serious adverse events or fatalities in the Favipiravir treated arm.
In the USA, Stanford University is conducting a phase II trial of 120 patients with mild coronavirus symptoms. This study was last updated on July 27, 2020. And a separate phase II study in the state of Massachusetts was last updated on September 9, 2020.
Avigan is not approved for distribution in the USA by the U.S. FDA.
Avigan (Favipiravir) Antiviral Medication Indication
Avigan (favipiravir) is effective against a wide range of types and subtypes of influenza viruses, including strains resistant to existing anti-influenza drugs, says a study published by the US NIH.
Of note is that favipiravir shows anti-viral activities against other RNA viruses such as arenaviruses, bunyaviruses, and filoviruses, all of which are known to cause fatal hemorrhagic fever. These unique anti-viral profiles will make Avigan a potentially promising drug for specifically untreatable RNA viral infections.
The main advantages of favipiravir are that it is administered orally and that it can be given in patients who are symptomatic but not ill enough to be hospitalized, stated a study published in September 2020.
As most COVID-19 patients (85%) have mild to moderate disease and can be treated at home, this drug could potentially be used in large numbers of patients. As with any antiviral, it should be stressed that favipiravir should be administered early after the onset of symptoms for it to be effective in reducing viremia. Its role in potentially shortening the duration of viral shedding could also have an epidemiological impact as it could reduce viral transmission at home and in the community
Avigan (Favipiravir) Antiviral Dosage
Approved for manufacture and sale in Japan as an influenza antiviral drug, Avigan, selectively inhibits RNA polymerase necessary for influenza virus replication.
The dosage of Avigan to treat COVID-19 disease patients is currently being evaluated in various clinical studies. In a phase 2 study in Boston, Massachusetts, Aviagn tablets are being evaluated: on the first day, once for 1600 mg, twice a day; From the 2nd day to the 10th day, once for 600 mg, twice a day; maximum of 10 days for oral administration of the drug.
However, reports indicate Avigan cannot be administered to expecting mothers or those who may become pregnant.
On September 2, 2020, a study from India found the side-effect profile of the drug also seems acceptable with asymptomatic hyperuricemia and mild, reversible elevation in transaminases being the most frequently reported adverse effects. In the Indian trial, no special safety signal was elicited. It is however teratogenic and must never be used in pregnant women.
The main disadvantage is a high pill burden which works out to a loading dose of 18-tablets on the first day and then 8-tablets a day for the rest of the course.
Avigan (Favipiravir) Antiviral News
- October 22, 2020 - Fujifilm Holdings Corp. announced it has partnered with Shanghai-based Carelink Pharmaceutical Co. to seek approval in China for Avigan to treat COVID-19 and influenza.
- October 20, 2020 - Appili Therapeutics Inc. announced that investigators enrolled and dosed the first cluster of participants in Appili’s CONTROL COVID-19 clinical trial.
- October 16, 2020 - FUJIFILM Toyama Chemical Co., Ltd. announced that the company filed an Application for Partial Changes to manufacturing and marketing approval matters of its anti-influenza drug Avigan® Tablet to the Ministry of Health, Labour and Welfare in Japan. The filing seeks to add an indication and other items relating to novel coronavirus infections (COVID-19).
- October 9, 2020 - Pre-clinical study: The potent antiviral efficacy of high favipiravir doses is in line with a recent study, in which thrice-daily dosing of ∼1,400 mg⋅kg−1⋅d−1 of favipiravir resulted in significant reductions in virus infection in hamsters. Favipiravir plasma exposures were consistent in both studies, although the doses used were not completely the same.
- October 3, 2020 - Moscow's Mayor Sobyanin said 'COVID-19 outpatients in Moscow will receive the antiviral drugs "Areplivir" and "Coronavir", which are versions of Avigan, for free.'
- September 24, 2020 - The Russian Direct Investment Fund (RDIF), Russia’s sovereign wealth fund, and ChemRar Group have agreed to supply Avifavir, the world's first registered favipiravir-based drug against coronavirus and Russia’s first drug approved for the treatment of COVID-19, to 17 countries. The drug has already been delivered to Belarus, Bolivia, Kazakhstan, Kyrgyzstan, Turkmenistan, and Uzbekistan.
- September 23, 2020 - FUJIFILM Toyama Chemical Co., Ltd. announced that the primary endpoint has been met in the phase III clinical trial of “Avigan Tablet” (generic name: favipiravir, “Avigan”) conducted in Japan for patients with novel coronavirus infections. Approved for manufacture and sale in Japan as an influenza antiviral drug, Avigan, selectively inhibits RNA polymerase necessary for influenza virus replication.
- September 18, 2020 - Russia based R-Pharm announced the approval of Coronavir for outpatient treatment of mild to moderate COVID-19 coronavirus infection. Coronavir is manufactured at R-Pharm’s facility in Yaroslavl, will be available in Russian pharmacies.
- September 11, 2020 - Appili Therapeutics Inc. announced that it has submitted a new protocol to its open investigational new drug application with the U.S. FDA to conduct a Phase 3 clinical study evaluating favipiravir in the early treatment outpatient setting for adult COVID-19 infections. Favipiravir is a broad-spectrum antiviral administered in oral tablet form.
- September 3, 2020 - The start of clinical trials for the Japanese flu drug, Avigan, in the Philippines has been delayed anew because the ethics board of the Department of Health has not given its approval for the participation of three of four local hospitals in the trials, Health Undersecretary Maria Rosario Vergeire said. Japan turned over the Avigan (favipiravir) tablets to the Philippines, which will be used by 100 patients with the coronavirus disease (COVID-19).
- September 2, 2020 - India review article 'Favipiravir: A new and emerging antiviral option in COVID-19.'
- August 19, 2020 - Dr. Reddy’s Laboratories Ltd. announced the launch of AVIGAN® (Favipiravir) 200 mg Tablets in India. The launch is part of the global licensing agreement with FUJIFILM Toyama Chemical Co. Ltd. that grants Dr. Reddy’s exclusive rights to manufacture, sell, and distribute AVIGAN (Favipiravir) 200 mg Tablets in India.
- August 17, 2020 - The Philippines started 9-month clinical trials for Avigan to study the efficacy of the anti-flu drug against the COVID-19 disease. Health Undersecretary Maria Rosario Vergeire said the clinical trials will include just four hospitals in Metro Manila.
- August 14, 2020 - Fujifilm Holdings Corp. announced it expects to complete clinical tests in Japan of the antiviral drug Avigan, a potential candidate treatment for COVID-19, in September, after a delay caused by difficulty in securing enough patient data.
- August 10, 2020 - Appili Therapeutics announced the U.S. FDA has granted the Company clearance to proceed after Appili’s filing of an investigational new drug application for broad-spectrum antiviral favipiravir, which is known as Avigan.
- August 4, 2020 - Sun Pharmaceutical Industries Ltd., the world's 4th largest generic pharmaceutical company, announced on Twitter that it will launch favipiravir (Avigan) under the brand ‘FluGuard’ at ₹35 per pill, making it the cheapest brand of the antiviral drug in India. Favipiravir is used to treat mild to moderate Covid-19 disease through an emergency use authorization from the Drug Controller General of India. ‘FluGuard’ is the sixth generic of favipiravir to be launched in India, with Glenmark Pharmaceuticals Ltd being the first to launch it in June after conducting a 150-patient clinical trial.
- August 4, 2020 - The Philippine government announced that it has begun clinical trials for Japanese anti-flu drug Avigan to see whether it would be effective in treating COVID-19, the disease caused by the new coronavirus.
- August 3, 2020 – Chromis, a joint venture established by the Russian Direct Investment Fund and ChemRar Group, announced the signing of a distribution agreement with South Africa’s 3Sixty Biopharmaceuticals, a subsidiary of 3Sixty Global Solutions Group, to deliver Avifavir, the first Russian anti-COVID drug, to South Africa.
- July 30, 2020 - The Philippine government said Thursday it will stockpile Japanese anti-flu drug Avigan, to treat severe cases of the new coronavirus, as planned clinical trials for the drug draw closer.
- July 28, 2020 - Fujifilm has not yet submitted the drug for approval to Japanese authorities as a treatment for COVID-19, and has said it will take that step as soon as possible. Health ministry official Yasuyuki Sahara said the government stands ready to review Avigan once Fujifilm submits it for approval. And, Stanford University is soon to start a phase II trial of 120 patients with mild symptoms and could move to a phase III around September, said Stanford professor Yvonne Maldonado.
- July 24, 2020 - Hyderabad: Optimus Pharma Pvt. Ltd Director P. Prashanth Reddy announced that their company had received approval from the Drugs Controller General of India (DCGI) to manufacture the active pharmaceutical ingredient, Favipiravir, through its subsidiary, Optrix Laboratories, and manufacture and market its antiviral drug, Favipiravir tablets. The drug was jointly developed by Cipla and the Council of Scientific and Industrial Research’s Indian Institute of Chemical Technology.
- July 22, 2020 - Glenmark Pharmaceuticals Ltd. announced top-line results from a Phase 3 clinical trial in mild to moderate COVID-19 patients conducted across seven clinical sites in India.
- July 18, 2020 - Fujifilm Holdings Corp. announced it will start a clinical study of the antiviral drug Avigan in Kuwait in collaboration with India's Dr. Reddy's Laboratories Ltd. and will involve up to 1,000 people to assess the flu drug's effectiveness as a COVID-19 preventive therapy.
- July 17, 2020 - The Kingdom of Saudi Arabia is set to play a key role in the development of a Russian COVID-19 vaccine that produced promising results in the first phase of human trials. Kirill Dmitriev, CEO of the Russian Direct Investment Fund, said the Kingdom could be part of Phase III, involving thousands of people, which is expected to begin in August 2020.
- July 13, 2020 - Glenmark Pharmaceuticals Ltd said it would lower the price of its generic version of favipiravir, FabiFlu, to 75 rupees ($0.9983) per tablet for restricted emergency use in patients with mild-to-moderate COVID-19 symptoms in India. Also, due to better yield and scale, Glenmark passes the benefits to patients by reducing the price of oral antiviral FabiFlu® by 27 % in India.
- July 1, 2020 - FUJIFILM Corporation announced a partnership with Dr. Reddy’s Laboratories Ltd. and Global Response Aid concerning the development, manufacture, and sales of Avigan® Tablets (favipiravir) which is a potential drug for the treatment of COVID-19 disease. Because it has a mechanism of action that selectively inhibits viral RNA polymerase, thereby preventing viral proliferation, Avigan may have an antiviral effect on the novel SARS-CoV-2 coronavirus, as it is classified into the same type of RNA virus as influenza viruses.
- June 30, 2020 - Stanford Medicine researchers are launching a clinical trial to test whether an oral drug can reduce symptoms and viral shedding in people with COVID-19. The researchers aim to enroll 120 participants, beginning July 6, who have been recently diagnosed with the disease but not been hospitalized.
- June 11, 2020 - Russian Direct Investment Fund and ChemRar Group have delivered the 1st batch of Avifavir drug against the coronavirus to Russian hospitals. As many as 60,000 courses of Avifavir will be delivered to Russian hospitals in June. Production of Avifavir could be increased to 2m courses per year if necessary. Clinics and pharmaceutical organizations in Moscow, Leningrad, Novgorod, Kirov, and Nizhny Novgorod regions, as well as in the Republic of Tatarstan and Ekaterinburg, have already received the first deliveries of the drug.
- June 8, 2020 - Fujifilm Holdings said it will continue clinical tests of its anti-influenza drug Avigan, a potential treatment for people infected with SARS-CoV-2 coronavirus, beyond the initially scheduled end in June 2020, due to a lack of sufficient data.
- June 2, 2020 - Dr. Monika Tandon, VP & Head, Clinical Development Global Specialty/Branded Portfolio, Glenmark Pharmaceuticals, told Telangana Today, “Combining antiviral agents that have a good safety profile and act on different stages of viral life-cycle is an effective treatment approach to rapidly suppress initial high viral load and lead to an overall improvement in clinical parameters.” Simultaneously Glenmark is also conducting phase 3 clinical trials of Favipiravir as a COVID-19 monotherapy option with 150 patients, enrolled from 9 leading government and private hospitals across India.
- June 1, 2020 - The Russian Direct Investment Fund, Russia’s sovereign wealth fund, and the ChemRar Group announced that Avifavir, Favipiravir-based drug, has received a temporary registration certificate from the Ministry of Health of the Russian Federation. Avifavir is Russia’s first COVID-19 drug and has shown high efficacy in treating patients with coronavirus during clinical trials.
- May 22, 2020 - Fujifilm Holdings Corp. said it is on course to supply the anti-influenza drug Avigan for 2 million COVID-19 patients by next March 2021, meeting a target set by the Japanese government to ramp up production of the potential treatment for the new coronavirus.
- May 20, 2020 - Avigan, a candidate drug for treating COVID-19, has not shown apparent efficacy in treating the respiratory disease in clinical trials so far, raising doubts about its approval by the end of this month as sought by the government, sources familiar with the matter. “There is currently no data showing that Avigan has high efficacy,” said Daisuke Tamura, an associate professor at Jichi Medical University specializing in pediatric infectious disease.
- May 15, 2020 - Favipiravir Observational Study Group (principal investigator: Dr. Yohei Doi, Fujita Health University) released a preliminary report of the Favipiravir Observational Study in Japan on the Japanese Association for Infectious Diseases website. Given that over 80% of COVID-19 patients have a mild disease which often improves by supportive therapy, caution is required in interpreting the efficacy of favipiravir based on the data presented here.
- May 13, 2020: The ChemRar Group and Russia’s sovereign wealth fund announced interim results of the multi-center, randomized, open comparative clinical trial of the drug Favipiravir (Avigan), in tablets, on patients hospitalized with COVID-19 disease.
- May 13, 2020: Japan’s health ministry decided to allow pharmaceutical companies to bypass standard clinical trial procedures to facilitate the fast-track approval of the anti-flu medicine Avigan as an early-stage treatment for COVID-19 disease.
- May 12, 2020: Glenmark Pharmaceuticals has initiated Phase 3 clinical trials in India on the antiviral tablet Favipiravir, for which it received approval from India’s drug regulator DCGI in late April. Clinical trials have commenced and over 10 leading government & private hospitals in India are being enrolled for the study. Glenmark estimates study completion by July/August 2020.
- May 4, 2020: Japanese Prime Minister Shinzo Abe said Monday he wants Avigan (favipiravir) approved for COVID-19 treatment in May, as Japan moves to fast-track approval for remdesivir as well.
- May 1, 2020: Japan will provide anti-flu drug Avigan free of charge to 43 countries for clinical studies on its efficacy as a coronavirus treatment, Foreign Minister Toshimitsu Motegi said to local media.
- April 30, 2020: FUJIFILM Diosynth Biotechnologies teams with COVID-19 Therapeutics Accelerator to reserve manufacturing capacity and provide technical expertise to deliver future COVID-19 therapies.
- April 30, 2020: Glenmark Pharmaceuticals announced that it has received approval from the Drug Controller General of India to conduct clinical trials on Favipiravir Antiviral tablets on COVID-19 disease patients. The product is a generic version of Avigan® of Fujifilm Toyama Chemical Co. Ltd., Japan, a subsidiary of Fujifilm Corporation.
- April 28, 2020: Japan will begin providing the anti-flu drug Avigan for free to 38 countries for treating patients with the new coronavirus.
- April 15, 2020: Fujifilm accelerates the production of its influenza antiviral drug “Avigan® Tablet” for COVID-19.
- April 9, 2020: Fujifilm announces the start of phase II clinical study of its influenza antiviral drug “Avigan® Tablet” (favipiravir) for patients with COVID-19, in collaboration with Brigham and Women’s Hospital, Massachusetts General Hospital and UMass Medical School. Avigan was approved in 2014 as an anti-influenza drug in Japan. Avigan selectively inhibits RNA polymerase, necessary for influenza virus replication.
- March 17, 2020: China's health leadership announced they have found the Japanese-developed anti-influenza drug Avigan to be effective in treating COVID-19 disease patients.
- February 17, 2020: The Taizhou government of Zhejiang province China announced Avigan (favipiravir) was approved for marketing.
- June 22, 2016: Fujifilm signs a patent license agreement on its anti-influenza drug Avigan Tablet* with China's major pharmaceutical company Zhejiang Hisun Pharmaceutical.
- November 11, 2015: Phase 3 Efficacy and Safety Study of Favipiravir for Treatment of Uncomplicated Influenza in Adults.
Avigan (Favipiravir) Clinical Trials
Clinical Trial NCT04346628: Oral Favipiravir Compared to Placebo in Subjects With Mild COVID-19 - last updated on July 27, 2020.
Clinical Trial NCT04349241: Efficacy and Safety of Favipiravir in Management of COVID-19 (FAV-001). This phase 3 clinical trial is to assess the safety and efficacy of favipiravir versus standard care therapy in the treatment of patients with COVID-19.
Clinical Trial NCT04358549: Study of the Use of Favipiravir in Hospitalized Subjects With COVID-19. This is an open-label, randomized, controlled, multicenter Phase 2 proof-of-concept study of favipiravir in hospitalized subjects with COVID-19.
Clinical Trial NCT04346628: Oral Favipiravir Compared to Standard Supportive Care in Subjects With Mild COVID-19. The objective of this Phase 2 study is to evaluate the efficacy of oral favipiravir compared with SOC in reducing the duration of viral shedding of SARS-CoV-2 virus in patients with uncomplicated COVID-19 disease.
Clinical Trial NCT04310228: Favipiravir Combined With Tocilizumab in the Treatment of Corona Virus Disease 2019. The purpose of this study is to evaluate the efficacy and safety of favipiravir combined with tocilizumab in the treatment of COVID-19 disease.
Clinical Trial NCT04319900: Clinical Trial of Favipiravir Tablets Combine With Chloroquine Phosphate in the Treatment of Novel Coronavirus Pneumonia. Estimated Study Completion Date: June 25, 2020
Clinical Trial NCT04303299: Various Combination of Protease Inhibitors, Oseltamivir, Favipiravir, and Hydroxychloroquine for Treatment of COVID19: A Randomized Control Trial (THDMS-COVID19.