Candidate: Favipiravir (marketed by Fujifilm as Avigan® and by Hisun in China as Favilavir)
Type: Broad spectrum anti-viral agent that is designed to selectively and potently inhibit the RNA-dependent RNA polymerase (RdRp) necessary for virus replication. Japan has approved Avigan for novel or re-emergent influenza and was previously used to treat Ebola patients in Guinea
2021 Status: PRESECO Enrollment Completed–Appili said September 17 that it completed patient enrollment in the viral shedding sub-study portion of its Phase III PRESECO (PREventing SEvere COVID-19) trial evaluating Avigan®/Reeqonus™ (favipiravir) as a potential early treatment in the U.S. for adults with COVID-19 and showing mild-to-moderate symptoms. The sub-study is now fully enrolled with more than 550 patients and full enrollment for the overall study is imminent, accordiong to the company.
The viral shedding sub-study is designed to identify COVID-19 variants in patients and evaluate the direct antiviral effect of favipiravir against SARS-CoV-2 and variants of the virus. Saliva samples are being collected daily from sub-study participants for viral load assessments and whole genome sequencing. Antiviral efficacy endpoints in study participants with detectable SARS-CoV-2 virus in saliva (defined as >100 RNA copies, using an RT-PCR assay) will be assessed from study day 3 onward and include time (number of days) to negative conversion (defined as <100 RNA copies) to study day 10.
The double-blind, placebo-controlled, randomized, multi-center superiority trial Iis enrolling participants at multiple clinical trial sites in the U.S., Brazil and Mexico.
Japan Trial Restarting–Fujifilm plans to restart a Japanese clinical trial designed to assess Avigan in COVID-19, Japan’s Nikkei newspaper reported on February 21. Two months earlier, an advisory panel to Japan’s Ministry of Health concluded that data from a earlier trial had been inconclusive, delaying approval of the drug in that country. The new study, which will involve about 270 patients, is intended to support a new authorization application planned for October.
2020 Status: Fujifilm said October 16 that it applied to Japan’s Ministry of Health, Labour and Welfare for an Application for Partial Changes expanding its manufacturing and marketing approval for Avigan, obtained in 2014, to include a COVID-19 indication. Fujifilm said it working to increase production of Avigan with strategic partners both inside and outside Japan, in order to deliver the treatment drug to COVID-19 patients “as soon as possible.”
Global Response Aid (GRA) and Dr. Reddy’s Laboratories, which license Avigan from Fujifilm Toyama Chemical, said September 23 that Avigan produced promising results in a single-blinded, placebo-controlled Phase III clinical study conducted in Japan and sponsored by FujiFilm Toyama. Patients who received Avigan recovered from COVID-19 symptoms 2.8 days earlier, on average, compared with the placebo group. Patients treated with Avigan also showed a statistically significant higher probability to recover compared with the placebo patients.
The Phase III trial aimed to measure patients’ recovery from pneumonia and COVID-19 symptoms by monitoring temperature, oxygen saturation and CT scan imaging of the lungs. The study’s 156 hospitalized patients showing COVID-19 induced pneumonia were divided into Avigan and placebo arms. A statistically significant percentage of the patients in the group receiving Avigan had a rapid reduction in viral loads, GRA and Dr. Reddy’s said.
Appili Therapeutics said August 10 it was granted FDA clearance to expand its Phase II clinical trial (NCT04448119) into the U.S. to assess the safety and efficacy of favipiravir tablets in controlling outbreaks following exposure to COVID-19 in long-term care facilities. Appili said it intends to enroll up to 760 participants in the trial across both the U.S. and in Canada. Health Canada provided regulatory clearance on May 21 for the Phase II study, designed to evaluate Fujifilm Toyama Chemical’s favipiravir as a preventative measure against COVID-19 outbreaks.
In the U.S., Avigan is also under study in a Phase II trial involving initially hospitalized COVID-19 patients, sponsored by FujiFilm Toyama; as well as an investigator-initiated Phase II study in mild or asymptomatic COVID-19 subjects, conducted by the Stanford University School of Medicine.
Russia and India have approved Favipiravir-based antiviral medications for emergency treatment of COVID-19, with additional trials of the antiviral drug in COVID-19 being conducted in countries that include the U.S., Japan, China, and the U.K.
On July 1, Fujifilm said its FUJIFILM Toyama Chemical subsidiary licensed exclusive rights to Dr. Reddy’s and GRA the exclusive right to develop, manufacture and sell Avigan outside Japan, in return for an undisclosed lump-sum license fee and royalties on sales. FUJIFILM Toyama Chemical also agreed to provide Dr. Reddy’s and GRA data on Avigan’s preclinical and clinical studies for use in carrying out clinical studies on COVID-19 patients in India, the Middle East, and “other regions where infections have been spreading.”
Fujifilm said April 15 it has expanded the manufacturing capacity of Fujifilm Toyama Chemical to increase production of Avigan® tablets. The company expects to progressively increase its monthly production of Avigan up to 100,000 treatment courses by July—2.5 times as much as March—and up to 300,000 treatment courses by September.
Earlier in April, Fujifilm launched its first U.S. clincal trial for Avigan in Massachusetts, where it is assessing the drug on approximately 50 COVID-19 patients at Brigham and Women’s Hospital, Massachusetts General Hospital, and the University of Massachusetts Medical School.
Japan’s Prime Minister Shinzo Abe told reporters in March that his government will partner with other countries to launch trials of on COVID-19 patients and ramp up its production, with plans to pursue approval if it succeeds in clinical trials now underway at Fujita Health University Hospital in Aichi Prefecture and other institutions, according to NHK. Japan’s government plans to stockpile 2 million treatment courses of Avigan as part of its emergency economic package, announced April 7.
Zhang Xinmin, an official at China’s Science and Technology Ministry, told reporters March 17 that favipiravir produced positive results in clinical trials in Wuhan and Shenzhen involving 340 patients—including a shortening of the time after treatment that patients tested negative for COVID-19 from 11 days to four, and improved lung conditions in 91% of treated patients vs. 62% of untreated patients, as measured via x-rays. Fujifilm has responded with a statement stressing that Avigan remained under study and had not been approved.
China’s stance contrasts with that of South Korea, where the Ministry of Food and Drug Safety has opted not to import Avigan for COVID-19, after a team of infectious disease experts concluded there was not enough clinical data to prove the drug’s efficacy. Citing unnamed sources, Politico reported March 31 that President Donald Trump’s administration sought FDA emertgency use authorization for Avigan following a conversation with Abe, and that the U.S. Department of Health and Human Services would not comment since it involved pre-decisional activity.
Japan’s Health Minister Katsunobu Kato said his ministry would recommend Avigan, developed by Fujifilm-owned Toyama Chemical, for use as a coronavirus treatment after test dosages appeared effective in mild and asymptomatic cases at least two medical institutions. In China, the National Health Commission approved Hisun’s version of the drug as an investigational treatment for SARS-CoV-2. Fujifilm granted Hisun a license in 2016 to use its Favipiravir-related patents in China to develop, manufacture and market an anti-influenza drug.
COVID-19: 200 Candidates and Counting
To navigate through the >200 potential therapeutic and vaccine options for COVID-19, GEN has grouped the candidates into four broad categories based on their developmental and (where applicable) clinical progress:
● FRONT RUNNER – the most promising therapeutics/vaccines based on clinical progress, favorable data or both.
● DEFINITELY MAYBE – earlier phases with promising partners, or more advanced candidates in development that have generated uneven data
● KEEPING AN EYE ON… – interesting technology, attracting notable partners, or both, but preliminary data.
● TOO SOON TO TELL – longshots pending additional experimental and/or clinical data.
GEN has also tagged the most common treatment types: