Generic Drug Giant Quietly Submits Marketing Authorization Application for Reeqonus (Favipiravir) in Canada

Generic Drug Giant Quietly Submits Marketing Authorization Application for Reeqonus (Favipiravir) in Canada TrialsiteN

Health Canada may be following India, Russia, some nations in Eastern Europe, and dozens of other nations who opt to use the antiviral medication Favipiravir (Avigan) to address early onset, mild to moderate SARS-CoV-2, the virus behind COVID-19. One of the world’s top generic drug producers, Dr. Reddy’s (NYSE:RDY) submitted an application for an expedited approval process for tablet form of favipiravir (Avigan®). As Health Canada “quietly accepted” the application, little attention has been placed on this important milestone in Western media. Many in the healthcare field have called out for the importance of generic, cost-effective, and widely available treatments for early onset COVID-19.  America itself had taken a serious look at favipiravir for purposes of antiviral investigations. TrialSite introduced that just five years ago, the U.S. Department of Defense (DoD) invested over $200 million to sponsor clinical trials investigating favipiravir. The antiviral drug that originates from Japan, favipiravir, is already approved in that nation for influenza. For COVID-19, favipiravir has already been approved or authorized on an emergency basis in places such as India and Russia where a generic form has been developed called Avifavir. Thus far, Health Canada has only approved two medications targeting COVID-19: remdesivir (Gilead) and the monoclonal antibody called Bamlanivimab, developed by Eli Lily Scientists in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID) and University of British Columbia spinoff AbCellera. A small biotech company known as Appili Therapeutics was the catalyst to get the favipiravir studies going in Canada. They then inked a deal with Dr. Reddy’s. Based in Halifax, Appili Therapeutics sponsors a couple studies in Canada, including one that centers on long-term care facilities (e.g. nursing homes) in that nation, which have seen horrific loss of life.

COVID-19 Second Wave in Canada

Canada’s COVID-19 crisis worsened significantly in this “second wave” of the pandemic to all time record numbers of cases, reports Charlie Pinkerton with Canada’s iPolitics. The overall death rate has gone down somewhat, partially explained by more knowledge and treatments for the novel coronavirus, however too much loss of life continues, partially explained by the lack of early stage onset treatment.

And the sheer number of cases threatens to overwhelm the capacity of Canada’s health system. For example, during the height of the first wave in early May, over 1,600 Canadians were becoming infected with SARS-CoV-2 per day. That number in the second wave most recently has gone up over 7,000 cases in a day on December 17.

iPolitics reported that as of this last Sunday, 507,795 cases of COVID-19 were reported in Canada along with 14,228 deaths associated with the virus. As the colder months approached, the cases steadily increased despite public health officials’ pleas to practice social distancing, wear masks and avoid certain local businesses. Now provincial governments are reintroducing lockdown measures in a bid to slow the spread of the pathogen. It would appear that Canada’s most populated province, Ontario, is headed toward a lockdown similar to the one in the spring when only essential businesses were allowed to remain open. The economic consequences to these lockdowns, especially in societies with little social safety net and where small business is a major employment driver, such as the United States, are severe.

Enter Favipiravir

Known as Avigan®, favipiravir is a broad-spectrum antiviral in oral tablet form developed by FUJIFILM Toyama Chemical Co., Ltd (FFTC) in Japan and approved in that nation in 2014 as a treatment and stockpile countermeasure for pandemic influenza. Some studies indicate it could be effective in the prevention of additional viruses, such as Ebola. Suspected to work similarly to remdesivir, which was the first drug approved by Health Canada to treat COVID-19, writes Mr. Pinkerton.

Following clinical studies, Russia and India recently approved favipiravir-based medications for the emergency use treatment against COVID-19.  FFTC recently announced positive Phase 3 data in use of Avigan in hospitalized COVID-19 patients. The Japanese health authority is taking its time in determining whether it will approve the drug or not. The health authority is struggling to conclude one way or the other, TrialSite reported just on December 17.

Indicating a move to drive commercialization, Indian generic giant Dr. Reddy’s (NYSE: RDY) and Dubai-based Global Response Aid recently received a license from FFTC for the manufacturing, development and commercial rights to favipiravir (Avigan tablets) outside of Japan, China and Russia. In China and Russia, generic producers are developing a form of favipiravir for COVID-19 prescriptions.

TrialSite has reported on favipiravir clinical trials around the world, including in the United States prominent studies led by principal investigator Dr. Yvonne Maldonado of Stanford University (NCT04346628) and a major Phase 2 study (NCT04358549) sponsored by Fujifilm with prominent trial site locations at Massachusetts General Hospital, Brigham and Women’s Hospital, Atlantic Health System and HonorHealth in Arizona.

The Application with Health Canada

Now Dr. Reddy’s is working closely with Health Canada on an expedited review of the favipiravir application, reported Vinod Ramachandran, Vice President and General Manager, Dr. Reddy’s Laboratories Canada Inc., reported The Hindu. Again, Dr. Reddy’s Laboratories Ltd partnered with Appili Therapeutics and Dubai-based Global Response Aid to commercialize the drug, including in Canada. The drug would be called Reeqonus and would be available in tablet form for treating COVID-19.

This application was submitted under Health Canada’s “Interim Order Respecting the Importation, Sale and Advertising of Drugs for Use in Relation to COVID-19” as reported in the Indian media.

This submission is based on an action in September when the Minister of Health in Canada signed an Interim Order essentially offering a new authorization pathway designed to help “expedite the authorization of drugs and vaccines for COVID-19,” reported The Hindu.

Avifavir’s Growing Influence

TrialSite reported in June that the Russia Ministry of Health issued a temporary registration certificate announcing that Avifavir became the world’s first Favipiravir-based drug to be approved for the treatment of COVID-19.  

The Russians were conducting at the time multiple studies in a number of cities. Led by Russian pharmaceutical company Chemrar, the Russians are now distributing Avifavir to a couple dozen nations, from those in Central Asia (Kazakhstan, Kyrgyzstan, Turkmenistan and Uzbekistan) to Baltics (Belarus) to Eastern Europe (Bulgaria, Serbia and Slovakia) to Latin and South America (Brazil, Chile, Columbia, Ecuador, El Salvador, Honduras, Panama, Paraguay and Uruguay) to Africa and the Middle East (South Africa, Saudi Arabia, Kuwait and the UAE), reported the RDIF (Russia’s sovereign wealth fund and drug development financier) to Reuters

U.S. DoD Trials

Favipiravir has already been thoroughly studied in human trials both outside the U.S. and within, and the antiviral has a well known safety profile. Just five years ago, over $200 million was allocated by the U.S. Department of Defense (DoD) in extensive studies investigating the safety and efficacy of the drug. TrialSite reported that it was somewhat odd that with the onset of the pandemic and given other nation’s interest, that little in the U.S. media mentioned the already extensive research associated with this drug.

The Austin Journal of Public Health Epidemiology (AJPHE) looked into the drug in the June article “Favipiravir and USA.” The author of that story, Chinmoy K Bose, noted that it “was invented as the most useful drug for bioengineered pandemics.” And while first developed in Japan, it has garnered a lot of interest, or at least it did so five years ago, from the Department of Defense.  U.S. clinical trials started in 2014 and completed in 2015, but there has been no FDA approval or market authorization. Interestingly, the author of the AJPHE story, Bose, shared that after twice corresponding with the U.S. Food and Drug Administration (FDA) it was found that no information would be available because of federal confidentiality.

Favipiravir in India

India now has several generic forms of favipiravir competing on the market there for mild to moderate COVID-19 cases. The emergency use authorization in the world’s second most populous nation was supported by studies over the summer, such as one study of 150 patients that found that those who received favipiravir were more likely to recover faster from the disease, and length of hospitalization was shorter than the standard of care group in a result strikingly similar to remdesivir. The study was published in the International Journal of Infectious Diseases. Medical scholars are split in that nation as many back the antiviral drug’s use for COVID-19 while some journalists are commissioned to write for peer review journals, such as Gayathri Vaidyanathan arguing against the urgent use of repurposed drugs for COVID-19 without more research.  TrialSite touched on this latter point in a July 24 piece titled “Favipiravir in India: Approved, Competition But What is Real Efficacy?

Status of Favipiravir R&D, Clinical & Commercialization Process in Canada

TrialSite reported on Appili Therapeutics efforts to commercialize favipiravir for COVID-19 earlier in the year. In November, again the Halifax-based biotech venture inked a collaborative drug development deal with Indian generic drug company Dr. Reddy’s and Global Response Aid. Appili had already entered into a licensing deal with the original pharmaceutical manufacturer of Favipiravir, FUJIFILM Toyama Chemical Ltd. of Japan, the originator of Avigan® tablets.

The agreements recently announced in November served to coordinate and accelerate the worldwide development, commercialization, and distribution of the favipiravir-based Avigan tablets for the potential treatment and prevention of COVID-19. This drug would fill a void in Canada, as there is currently in Canada no therapy that be prescribed on an ambulatory, outpatient basis. Many physicians call out the importance for treatment options for the individual that receives a positive COVID-19 diagnosis but may have few if any symptoms. A growing chorus around the world declares that treatments must be given to individuals early on—that patients shouldn’t just be sent home and told to rest and wait to see what happens.

Long-term Care Mortality

As TrialSite has chronicled, COVID-19 has represented an unacceptable death rate for the elderly in both the United States and Canada. In Canada, over 80% of the deaths at least by June were associated with nursing homes.  

TrialSite showcased some Canadian research that found some factors associated with why death rates were higher in Ontario-based long-term care facilities versus British Columbia. Something had to be done to protect this vulnerable population.

Back in June Appili Therapeutics, thanks to Health Canada’s greenlight, initiated a study of favipiravir in long-term care facilities. The study sought to discover if the use of favipiravir could help stop or at least slow down outbreaks in long-term care facilities. This study is led by Toronto-based investigators from Sinai Health System’s Lunenfeld-Tanenbaum Research Institute and St. Michael’s Hospital.

According to Clinicaltrials.govthe study finally started in October and runs till March 2021. A randomized controlled trial targeting 760 participants, its formal title is “Control of COVID-19 Outbreaks in Long Term Care (CONTROL-COVID).”

The CONFROL-COVID study is led by Principal Investigator Allison J. McGeer, MD, FRCPC, Microbiologist and Infectious Disease Consultant with Mount Sinai Hospital

Call to Action: TrialSite will monitor the process associated with Health Canada’s review of favipiravir for early stage COVID-19 treatment.