Glenmark to start new Phase 3 clinical trial on a combination of two anti-viral drugs in hospitalized patients of moderate COVID-19 in India

The two antiviral drugs have different mechanism of action, and theircombination may demonstrate improved treatment efficacy by effectively tackling high viralloads in patients during early stage of disease. 

Early administration of a combination of antiviral medications acting by different mechanisms isdesirable for the treatment of COVID-19, since the viral load of SARS-CoV-2 peaks around thetime of symptom onset.2 Thus combining antiviral drugs could result in greater clinicaleffectiveness and could also prevent, or delay, the emergence of resistance. 

Favipiravir is an oralantiviral drug approved in Japan since 2014 for the treatment of novel or re-emerging influenzavirus infections.3 It has a unique mechanism of action by which it inhibits viral replication: it isconverted into an active phosphoribosylated form (favipiravir-RTP) in cells and recognized as asubstrate by viral RNA polymerase, thereby inhibiting RNA polymerase activity that is requiredfor viral replication.

Umifenovir is another oral antiviral drug licensed for the treatment andprophylaxis of influenza A and B infections in Russia and China.

Umifenovir impedes the viralattachment to cells and acts as a viral entry inhibitor.5 Additionally it exhibits modulatory effects on the immune system and induces interferon-production. 

Hence, a combined use of Favipiravirand Umifenovir acting on different mechanisms offers a comprehensive antiviral cover on preentry and post-entry life-cycle of the SARS-CoV-2 virus. 

Both Favipiravir and Umifenovir inhibitedvirus infection in vitro5,6 and have shown efficacy in COVID-19 clinical trials. The currentGlenmark study will examine whether early administration of a combination of Favipiravir andUmifenovir, both acting by different mechanisms, enhances antiviral efficacy on COVID-19patients. 

Commenting on this development, Dr. Monika Tandon, Vice President & Head, ClinicalDevelopment Global Specialty/Branded Portfolio, Glenmark Pharmaceuticals Ltd., said,“Combining antiviral agents that have a good safety profile and act on different stages of virallife-cycle is an effective treatment approach to rapidly suppress initial high viral load and leadto overall improvement in clinical parameters."

"We consider Glenmark’s study will be pivotal inleading to identification of highly effective and safe treatments against COVID-19 in India.Beyond its many potential patient treatment benefits, we also hope the combination therapywill reduce infection risk amongst medical professionals and healthcare workers by reducingthe duration of virus shedding from treated patients," Tandon said.

Further, Sujesh Vasudevan, President, India Formulations, Middle East and Africa business,Glenmark Pharmaceuticals Ltd. mentioned “This is another step in our effort is to launch atreatment for COVID-19 patients and we are looking at every possibility. We will do all it takesto ensure accessibility of the product across the country if the clinical trials are successful.” 

The new combination clinical trial will be called FAITH – (FA vipiravir plus Um I fenovir (efficacy& safety) T rial in Indian H ospital setting). 158 hospitalized patients of moderate COVID-19infection will be enrolled in the combination study and randomized in two groups: one groupreceiving Favipiravir and Umifenovir (with standard supportive care); and one group receivingFavipiravir along with standard supportive care. Patients in the arm receiving the drug will receiveFaviprivir 1800mg bid and Umifenovir 800 mg bid on Day 1. 

Thereafter, patients would receiveFaviprivir 800mg bid and Unifenovir 800mg bid for the remaining course of the treatment.Duration of treatment will be 14 days and patients will be discharged after clinical cure and twoconsecutive negative tests for COVID-19 based on RT-PCR. 

Simultaneously, Glenmark is also conducting phase 3 clinical trials of Favipiravir as a COVID-19monotherapy option with 150 patients, enrolled from 9 leading government and privatehospitals across the country. So far 30 patients have been randomised.

The monotherapy phase3 clinical trial results are expected by July/August 2020. Glenmark was the first pharmaceutical company to receive approval from drug regulator DCGI to conduct Favipiravir clinical trialsagainst COVID-19 in India.