Favipiravir COVID-19 Japan Phase III study is successful, will submit a marketing application in October
Introduction: On September 23, 2020, the Fujifilm Group announced that the Phase III clinical trial of favilavir in Japan for the treatment of COVID-19 has reached the primary endpoint. The Fujifilm Group stated that it will conduct a detailed analysis of the research results and submit an application for listing of new indications as early as October.
SOURCE: PHARMCUBE (医药魔方)
NEWS RELEASE
Anti-influenza drug Avigan® Tablet
Meets Primary Endpoint in Phase III Clinical Trial in Japan for COVID-19 patients
TOKYO, September 23, 2020—FUJIFILM Toyama Chemical Co., Ltd. (President: Junji Okada; hereinafter “FUJIFILM Toyama Chemical”) has announced today that primary endpoint has been met in phase III clinical trial of “Avigan Tablet” (generic name: favipiravir, “Avigan”) conducted in Japan for patients with novel coronavirus infections (hereinafter “COVID-19”). The efficacy primary endpoint is time to negative conversion of detectable SARS-CoV 2 viral RNA in the RT-PCR assays, and to alleviation of symptoms (body temperature, oxygen saturation and chest images).
FUJIFILM Toyama Chemical began a phase III clinical trial of Avigan in Japan in March 2020, for COVID-19 patients with non-severe pneumonia. The company conducted randomized, placebo-controlled, single-blind comparative study*1 to evaluate the efficacy and safety of Avigan.
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
The trial is a randomized, placebo-controlled, single-blind phase III clinical study for non-severe COVID-19 patients, which was launched in Japan in March 2020. The time of SARS-CoV2 virus RNA turning negative and the time of remission of symptoms (body temperature, blood oxygen saturation and chest imaging) detected by RT-PCR of the primary endpoint of the study.
The results of the study of 156 patients showed that the median time to remission in the favilavir treatment group was 11.9 days, compared with 14.7 days in the placebo group, which was statistically significant (p=0.0136), and the adjusted HR was 1.593 (95% CI 1.024 –2.479). No new safety issues were observed in this study.
Haizheng Faviravir tablets are being produced Source: Internet
This is not the first time that favilavir has been proven to be effective against the new crown virus. As early as this year, favilavir has shown its first appearance in two experiments conducted by the Third People’s Hospital of Shenzhen, China and Zhongnan Hospital of Wuhan University, China. Officially recommended by the Ministry of Science and Technology of China.
TAIZHOU, China, June 23, 2020 /PRNewswire/ -- Favipiravir is a broad-spectrum antiviral agent that inhibits the RNA-dependent RNA polymerase of RNA viruses. It has efficacy against a range of RNA viruses, including Ebola, influenza and COVID-19. No evident adverse reactions have been found since it came into the market. Unlike traditional antiviral drugs, Favipiravir can directly prevent the virus from replicating itself in cells, with a mechanism of action similar to Remdesivir.
The Chinese Ministry of Science and Technology officially recommends favilavir to be included in the diagnosis and treatment guidelines. Source: US FOX official website
Favilavir is currently carrying out a global multi-center clinical trial for the treatment of COVID-19. From the clinical data that has published the results, Favilavir can quickly clear the virus and achieve the effect of alleviating the symptoms of COVID-19, with less Adverse reactions, and higher tolerance.
It is worth mentioning that in various related studies and multi-country new crown diagnosis and treatment guidelines, the dosage and administration time of favilavir are higher than those recommended in the instructions. The first day's dose is 3200mg-3600mg, the next day's dose is 1200mg-1600mg/day, and the treatment time is 7-14 days.
With the continuous advancement of various trials, we can see that favilavir is constantly fulfilling its potential for the treatment of new coronaviruses.
Favilavir is an RNA polymerase (RdRp) inhibitor, a broad-spectrum anti-influenza virus drug, approved in Japan on March 24, 2014 for the treatment of new and recurrent influenza.
Zhejiang Hisun Pharmaceutical Co., Ltd. exclusively authorized Hisun Pharmaceutical from Toyama Chemical Industry Co., Ltd. of Japan for the patent of Favilavir. On February 15, 2020, favilavir was approved for listing in China.
Since its listing, Hisun Faviravir tablets have assisted more than 20 countries and regions. The COVID-19 indications of Hisun Faviviravir tablets are currently under development.
WHO Announced That: COVID-19 Has Developed into A Global Pandemic
Horrible Coronavirus Family and SARS-Cov-2
SARS-CoV-2 virus that caused COVID-19 stemed from infamous coronavirus family, which is an enveloped, positive-sense and single-stranded RNA beta-coronavirus.
An analysis on the origin and evolution of 7 coronaviruses known to infect humans published in Nature reviews. Microbiology in 2018 showed:
5 human coronaviruses were originated from bats
which included severe SARS, MERS viruses
The research results obtained by Shi Zhengli and Zhou Peng team from Wuhan Institute of Virology that was published online on BioRxiv platform showed that:
- SARS-CoV-2 has 96% homology with a bat coronavirus found in Yunnan, basically confirming that bat is the origin of SARS-CoV-2
• The latest research results published by Chinese scientists in the English version of SCIENCE CHINA Life Sciences showed that:
It is adjacent to SARS virus and SARS-like virus groups. On the basis that its evolutionary neighbors and outer groups were all found in various bats.
It is inferred that its natural host may also be bats, but it's still unsure whether there is an unknown intermediate host medium or not
SARS-CoV-2 Is Homologous to SARS Virus with Highly Similar Structure
Coronavirus Study Group of the International Committee on Taxonomy of Viruses: named the novel coronavirus as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
SARS-CoV-2 is genetically similar to SARS associated coronavirus, belonging to the same cluster
The structure of S protein is highly similar to that of the corresponding region of SARS-CoV
The S protein structure (blue structure) of SARS- CoV-2 is highly coincident with the S protein (red structure) of SARS-CoV
SARS-CoV-2 Has Similar Pathogenic Mechanism with SARS Virus
SARS-CoV-2 could mediate infection through ACE2 in human body
The host cell receptor of SARS virus has been confirmed to be ACE211
It's found through modeling that: the S protein of SARS-CoV-2 has a relativley high binding strength with ACE2, indicating that ACE2 is highly likely to host cell receptor2-3
Have some similar symptoms, such as fever, dry cough and dyspnea
matic Diagram for the Interaction Between SARS-Cov-2 S protein homology modeling structure and ACE2
ACE2 is distributed throughout the body and closely associated with cardiovascular diseases
ACE2 is widely expressed in human heart, kidney, small intestine, ovary, lung, liver, pancreas, eye as well as other organs and tissues
ACE2 is an important regulator in the cardiovascular system, which is inseparable from the structure protection and functional regulation of cardiovascular
After analyzing 70,000 cases, China CDC found that: the overall crude fatality rate was 2.3%, and the fatality rate of special populations was even higher, especially the cardiovascular disease population with a fatality rate as high as 10.5%
WHO — Seven Differences Between COVID-19 and Influenza
Targeted Antiviral Drugs Opened A New Chapter of Targeted Antiviral Treatment of COVID-19
Potential targets of anti-coronavirus drugs: viral target + host target
Nature Review
Currently, targeted drugs are an important direction for screening COVID-19 therapeutic drugs, with 7 viruses targets and 3 host targets
RNA polymerase inhibitors have attracted most attentions, as many as 4, all of which have entered clinical trials. This kind of drugs could be used by RdRP to synthesize RNA strand, but after integrating into RNA strand, they would block RNA strand to continue to be synthesized, allowing RNA strand synthesis to be early terminated. termination
Could be used to treat broad-spectrum RNA viruses (including coronavirus), mainly including the following drugs
RNA Polymerase Inhibitors Have Become the Focus of Potential Therapeutic Drug Screening for COVID-19
The Joint Prevention and Control Mechanism of the State Council pointed out at a press conference held in Beijing on February 15 that, a batch of drugs such as chloroquine phosphate, Remdesivir and Favipiravir have been put into clinical trials successively, and some drugs have initially shown good clinical efficacy.
RNA polymerase inhibitor, accounting for 2/3
An article published in Cell Research on February 4, 2020 stated that these three drugs could all inhibit 2019-nCoV infection in vitro2 Favipiravir and Remdesivir are both RNA polymerase inhibitors, the mechanisms of which have commonality
The world's first infected person accepting Remdesivir treatment started bringing down fever on the second day upon treatment, with no need to inhalate oxygen any more, whose blood oxygen saturation also returned to 94%-96%
RNA Polymerase Inhibitors Have Become the Focus of Potential Therapeutic Drug Screening for COVID-19
On February 15th, "Favipiravir” developed by Zhejiang Hisun Pharmaceutical Co.,Ltd. was officially approved by the National Medicine Products Administration for launch, which became the first medicine that have been approved for launch domestically during the epidemic
Favipiravir is a new broad-spectrum antiviral drug of RNA-dependent RNA polymerase (RdRp) inhibitor. Its original product AVIGAN® is developed by Fujifilm Group Toyama Chemical Co. Ltd., which was approved for lauching in Japan in March 2014, acting as a national reserve medicine in Japan for the treatment of novel and recurrent influenza.
Favipiravir was originally developed and manufactured by Toyama Chemical (Fujifilm group) and was approved for medical use in Japan in 2014. In 2016, Fujifilm licensed API for it to Zhejiang Hisun Pharmaceutical Co. of China.
Mechanism of action
Favipiravir exerts its anti-viral activity as a pro- drug, since Favipiravir is intra-cellularly hosphoribosylated to be an active form, Favipiravir-RTP, which inhibits the viral replication by interacting with viral RNA polymerase.
Favipiravir is incorporated into cells, and converted to Favipiravir ribofuranosyl phosphates by host cell enzymes. The triphosphate form, Favipiravir-RTP, inhibits the influenza viral RNA polymerase activity.
Favipiravir may be misincorporated in a nascent viral RNA, thus preventing incorporation of nucleotides for viral RNA replication and transcription.
Pharmacokinetic parameters showed high bioavailability and rapid onset
Parameters
Data of Favirpiravir
Oral bioavailability
high（ ＞ 95 %)
Tmax
0 .5 - 3h
Plasma concentration
Cmax： 35 – 50 mg/ ml
Human serum protein binding rate
54%
average half- l i fe values
2 - 5. 5h
Metabolism of Favipiravir
HISUN Profile
Zhejiang Hisun Pharmaceutical Co., Ltd. was founded in 1956. In 2000, Hisun issued A-shares in Shanghai stock exchange, but it continues to remain a state-owned enterprise. Hisun is one of the largest antibiotics and anti-tumor drug production bases in the country. It has won several titles, including first batch of innovative enterprises, national technology innovation demonstration enterprises, and "National Industrial Brand Demonstration Enterprise” of the Chinese Ministry of Industry and Information Technology. Hisun has also been named to “Top Domestic Industrial Manufacturing 500”, “China's top 100 pharmaceutical enterprises", "Top 100 pharmaceutical international enterprises", “China's innovative pharmaceutical companies", and “China's top 100 drug research and development" among others.
Hisun began as a small chemical factory and entered the pharmaceutical field in the early 1970s. Since its founding over 60 years ago in 1956, Hisun has amassed a total asset worth of 21.8 billion RMB. While Hisun is primarily engaged in the R&D, manufacturing, and sales and marking of API and final dosage forms of chemical and biological drugs, its core business has extended to include branded generic drugs, biosimilarst and other innovative drugs. Today, Hisun operates as a comprehensive biopharmaceutical technology group with multiple business segments in several therapeutic areas, and a full-value chain of R&D, manufacturing, and sales and marketing.80% of Hisun’s active pharmaceutical ingredients export overseas.
Contact Information
ZHE JIANG HISUN PHARMACEUTICAL CO., LTD.
Headquarter: Tai Zhou, China http://www.hisunpharm.com
