Mumbai Hospital-led Phase 3 Clinical Trial Reveals the Efficacy of Favipiravir Targeting Mild to Moderate COVID-19 Patients in India

Mumbai Hospital-led Phase 3 Clinical Trial Reveals the Efficacy of Favipiravir Targeting Mild to Moderate COVID-19 Patients in India

Glenmark Pharmaceuticals, a prominent Indian pharmaceutical firm, reports that the oral antiviral drug originating in Japan, Favipiravir, prevents the replication phase of SARS-CoV-2, the virus behind COVID-19. The findings associated with a Phase 3 clinical trial are published in the peer reviewed International Journal of Infectious Diseases. TrialSite has consistently chronicled the unfolding Favipiravir research across nations. The drug has been approved to treat COVID-19 in Russia (Avifavir) and other countries in Eastern Europe. The drug is in use in China and India on an emergency use basis to deal with the pandemic. Approved in Japan in 2014 for influenza (Avigan), the drug was intensively tested by the U.S. government in 2015 with over $200 million worth of research leading to no disclosed results. In India, the market for early stage onset COVID-19 heats up as multiple firms are producing generic products based on Favipiravir—which went off patent in 2019.  With a few clinical trials occurring in North America based on Favipiravir (e.g. Stanford University, Boston Medical Center and others), TrialSite suggests that national research agencies still consider supporting research into lower cost investigational products that potentially help the patient with that critical early onset COVID-19 stage on an outpatient or prescribed home-care basis.

The latest news out of India is promising as the results of this Phase 3 clinical trial sponsored by Glenmark Pharmaceuticals and led by the Breach Candy Hospital Mumbai were published online in The International Journal of Infectious Diseases (IJID). This is a globally reputed peer-reviewed, pubmed indexed, open access journal with monthly issues, published by the International Society for infectious Diseases in the Untied States. These findings will appear in the print edition as well. The publication of the study is titled Efficacy and Safety of Favipiravir, an oral RNA-Dependent RNA Polymerase Inhibitor, in Mild-to-Moderate COVID-19: A Randomized, Comparative, Open-Labe, Multicenter, Phase 3 Clinical Trial authored by Dr. Zarir F. Udwadia and co-authors.

The Study Drug

Favipiravir is an antiviral medication that works by inhibiting a viral enzyme called RdRP (RNA dependent RNA polymerase), thereby halting the virus’s replication cycle. This helps control the multiplication of the virus and prevents its spread in the patient. This mechanism of action of Favipiravir is novel compared to most antivirals that primarily prevent entry and exit of the virus from cells. Several published reports are now available pointing to at least some moderate effectiveness against COVID-19.

This Phase 3 clinical trial involved a branded version Favipiravir. Developed by Glenmark Pharmaceuticals, Trialsite has followed the development of FabiFlu® in India. 

It is based on Favipiravir, which is also known as Avigan in Japan. Approved there for influenzas, its maker FUJIFILM Toyama Chemical Co. recently submitted an application to that nation’s health authority to market the drug there targeting COVID-19. No decision has been passed down as of yet.

The drug was approved to treat influenza in Japan in 2014 and became a generic drug in 2019. It is apparently licensed for production and distribution in China by Zhejiang Hisun Pharmaceutical Co.

The Study

The Phase 3 study was conducted in 150 patients as part of a randomized, open label, multicenter effort to investigate the efficacy and safety of Favipiravir plus standard supportive care (Favipiravir treatment arm), versus standard supportive care alone (control arm), in mild to moderate patients, randomized within a 48 hour window of testing RT-PCR positive for COVID-19. 

Glenmark Pharmaceutical reports that the drug offered multiple treatment benefits including faster time to clinical cure and it actually contributed to the delay in the need for supportive oxygen therapy. Moreover, the investigators, led by Dr. Zarir F. Udwadia, MD, FRCP, FCCP, Breach Candy Hospital Mumbai, that patients with COVID-19 with moderate symptoms were discharged from the hospital earlier than those patients that did not receive Favipiravir, with the median time to clinical cure reduced by 2.5 days compared with the control group.

Patients in the Glenmark clinical trial received Favipiravir tablets 3,600 mg (1,800 mg BID) (Day 1) + 1,600 mg (800 mg BID) (Day 2 or later) for up to maximum of 14 days, along with standard supportive care. Randomization was stratified based on disease severity into mild and moderate. The drug was well tolerated with no serious adverse events (SAEs) or deaths in the Favipiravir arm of the study.

Principal Investigator Point of View

According to Dr. Zarir Udwadia, “Every claim for the efficacy of a new drug in COVID-19 must be backed by evidence from a clinical trial. Glenmark has done just that with Favipiravir. Their well-designed trial in 150 patients showed Favipiravir resulted in a significantly improved time to clinical cure and rapid viral clearance. Based on this I would consider the use of this anti-viral drug in symptomatic patients with mild to moderate COVID-19. I eagerly await the results of similar trials presently being conducted in Boston and at Stanford.”

Competition with Remdesivir

Although the pivotal Phase 3 study that led to remdesivir approval in the United States showed that remdesivir performed slightly better than Favipiravir here, (4 to 5 days reduction in illness vs. 2.5 days) it should be noted A) Remdesivir is much more expensive, especially in the U.S.; B) Remdesivir cannot be conveniently used on an at home or outpatient basi;s C) it must be intravenously administered vs. convenience and economy of pill form for Favipiravir in India; and D) the recent  World Health Organization Solidarity Trial revealed that Remdesivir doesn’t even impact COVID-19 patients in any meaningful way,  while many physicians increasingly question the value of the drug in the epidemic.  

TrialSite has recorded enough real world cases suggesting, to the staff, that Remdesivir does make an impact and certainly has a place in treating COVID-19. But for those patients in India with mild to moderate COVID-19 that must heal at home, perhaps Favipiravir could be a superior choice? The Indian medical community and regulators will certainly consider what is best for the citizenry there.

Emergency Approval in India 

In June 2020, Glenmark received manufacturing and marketing approval from India’s drug regulator for Favipiravir (FabiFlu®), making it the first oral approved medication in India for the treatment of mild to moderate COVID-19. The manufacturing and marketing approval was granted as part of an accelerated approval process, considering the emergency situation of the COVID-19 outbreak in India. The approval’s restricted use entails responsible medication use where every patient must have signed informed consent before treatment initiation.

About Glenmark Pharmaceutical

Glenmark Pharmaceuticals Ltd. (GPL) is a global research-led pharmaceutical company with presence across Generics, Specialty, and OTC business with operations in over 50 countries. Glenmark’s key therapy focus areas globally are respiratory, dermatology and oncology. It is ranked among the top 80 Pharma & Biotech companies of the world in terms of revenue (SCRIP 100 Rankings published in the year of 2019)

Lead Research/Investigator

Dr. Zarir F. Udwadia, MD, FRCP, FCCP, Breach Candy Hospital Mumbai

Call to Action: TrialSite welcomes your comments on Favipiravir and the pandemic. Should Operation Warp Speed be looking into lower cost options for early onset COVID-19 for mild to moderate cases or given the recent great news about vaccine effectivity is this not required anymore?