Remdesivir: Critical Clinical Appraisal for COVID 19 Treatment

Abstract

Remdesivir is presently been considered as ‘molecule of hope’ to curb the menace of COVID19. Non-availability of any USFDA approved drug has led to several attempt of drug-repurposing and development of new therapeutic molecules. However, Remdesivir has been found to be effective against a broad range of virus including SARS, MERS and COVID 19 through in-vitro studies. Several clinical research attempt are presently being conducted showing promising result yet not conclusive. This review summarized all such clinical trials to critically appraise the usage of Remdesivir against COVID 19 along with the publications related to the results of the clinical studies. The present regulatory aspect i. e. Emergency Use Authorization (EYA) and information of molecule and plausible mechanism is also dealt.

Key words

remdesivir - COVID-19 - clinical studies - treatment - compassionate use - USFDA

Publication History

Received: 29 May 2020

Accepted: 06 October 2020

Article published online:
29 October 2020

• References

• 1 National Center for Immunization and Respiratory Diseases (NCIRD), Division of Viral Diseases. Information for Clinicians on Investigational Therapeutics for Patients with COVID-19. https://www.cdc.gov/coronavirus/2019-ncov/hcp/therapeutic-options.html
• 2 Drugbank: https://www.drugbank.ca/drugs/DB14761
• 3 Stephens, Bret (18 April 2020). "The Story of Remdesivir". The New York Times. p. A23. Retrieved May 2020. https://www.nytimes.com/2020/04/17/opinion/remdesivir-coronavirus.html
• 4 Warren TK, Jordan R, Lo MK. et al. Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys. Nature 2016; 531: 381e385
• 5 Gordon CJ, Tchesnokov EP, Woolner E. et al. Remdesivir is a direct- acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potency. J Biol Chem 2020; https://doi.org/10.1074/jbc.RA120.013679
• 6 Agostini ML, Andres EL, Sims AC. et al. Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease. MBio 2018; 9: e00221ee00218
• 7 Coronavirus (COVID-19) Update: FDA Issues Emergency Use Authorization for Potential COVID-19 Treatment. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-issues-emergency-use-authorization-potential-covid-19-treatment
• 8 https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization#covidtherapeutics
• 9 Saha A, Sharma AR, Bhattacharya M. et al. Probable Molecular Mechanism of Remdesivir for the Treatment of COVID-19: Need to Know More. Archives of Medical research. 2020; https://doi.org/10.1016/j.arcmed.2020.05.001
• 10 USFDA Fact Sheet For Health Care Providers: https://www.fda.gov/media/137566/download
• 11 Grein J, Ohmagari N, Shin D. et al. Compassionate Use of Remdesivir for Patients with Severe Covid-19. N Engl J Med 2020; 382: 2327-2336 DOI: 10.1056/NEJMoa2007016.
• 12 https://www.ema.europa.eu/en/documents/other/summary-compassionate-use-remdesivir-gilead_en.pdf
• 13 Javorac D, Grahovac L, Manić L. et al. An overview of safety assessment of the medicines currently used in the treatment of COVID-19 disease [published online ahead of print, 2020 Jul 21]. Food Chem Toxicol 2020; 144: 111639 DOI: 10.1016/j.fct.2020.111639.
• 14 Chatterjee S. Status of Remdesivir: Not Yet Beyond Question!. Arch Med Res 2020; Sep 21 S0188-S4409; 30877-8. doi: 10.1016/j.arcmed.2020.09.004. Epub ahead of print. PMID: 32972773; PMCID: PMC7505045.
• 15 Musa A, Pendi K, Hashemi A. et al. Remdesivir for the Treatment of COVID-19: A Systematic Review of the Literature. West J Emerg Med 2020; 21: 737-741. Published 2020 May 20. doi:10.5811/westjem.2020.5.47658
• 16 NIH: US National Library of Medicine https://clinicaltrials.gov/ct2/home
• 17 Wang Y, Zhang D, Du G. et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet 16.05.2020; 395: 1569-1578 DOI: 10.1016/S0140-6736(20)31022-9..
• 18 Mulangu S, Dodd LE, Davey RT. et al. A Randomized, Controlled Trial of Ebola Virus Disease Therapeutics. N Engl J Med 12.12.2019; 381: 2293-2303 DOI: 10.1056/NEJMoa1910993.
• 19 Beigel JH, Tomashek KM, Dodd LE. et al. Remdesivir for the Treatment of Covid-19 - Preliminary Report [published online ahead of print, 2020 May 22]. N Engl J Med 2020; DOI: 10.1056/NEJMoa2007764.
• 20 Nakkazi E. Randomised controlled trial begins for Ebola therapeutics. Lancet 2018; Dec 1 392: 2338 DOI: 10.1016/S0140-6736(18)33011-3.
• 21 Antinori S, Cossu MV, Ridolfo AL. et al. Compassionate remdesivir treatment of severe Covid-19 pneumonia in intensive care unit (ICU) and Non-ICU patients: Clinical outcome and differences in post-treatment hospitalisation status. Pharmacol Res 2020; 158: 104899 doi: 10.1016/j.phrs.2020.104899. Epub 2020 May 11. PMID: 32407959; PMCID: PMC7212963
• 22 Humeniuk R, Mathias A, Cao H. et al. Safety, Tolerability, and Pharmacokinetics of Remdesivir, An Antiviral for Treatment of COVID-19, in Healthy Subjects. Clin Transl Sci 2020; 13: 896-906. doi: 10.1111/cts.12840 Epub 2020 Aug 5. PMID: 32589775; PMCID: PMC7361781
• 23 Spinner CD, Gottlieb RL, Criner GJ. et al. Respuestas rápidas a la pandemia de COVID-19 a través de la ciencia y la colaboración global: el ensayo clínico Solidaridad. Rev Peru Med Exp Salud Publica 2020; 37: 356–360 Spanish. doi: 10.17843/rpmesp.2020.372.5546. Epub 2020 Aug 28. PMID: 32876229
• 24 Soto A, Quiñones-Laveriano DM, Garcia PJ. et al. Respuestas rápidas a la pandemia de COVID-19 a través de la ciencia y la colaboración global: el ensayo clínico Solidaridad. Rev Peru Med Exp Salud Publica 2020; 37: 356-360 Spanish. doi: 10.17843/rpmesp.2020.372.5546. Epub 2020 Aug 28. PMID: 32876229