Treatment of Coronavirus Disease 2019 (COVID-19): Investigational Drugs and Other Therapies Updated: Apr 15, 2020 Author: Scott J Bergman, PharmD, FCCP, FIDSA, BCPS, BCIDP; remdesivir (GS-5734; Gilead Sciences, Inc) is a nucleotide analog prodrug. It was studied in clinical trials for Ebola virus infections but showed limited benefit. [17] Remdesivir has been shown to inhibit replication of other human coronaviruses associated with high morbidity in tissue cultures, including severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012. Efficacy in animal models has been demonstrated for SARS-CoV and MERS-CoV. [18] Several phase 3 clinical trials are testing remdesivir for treatment of COVID-19 in the United States, South Korea, and China. An adaptive randomized trial of remdesivir coordinated by the National Institute of Health (NCT04280705) was started first against placebo, but additional therapies can be added to the protocol as evidence emerges. The first experience with this study involved passengers of the Diamond Princess cruise ship in quarantine at the University of Nebraska Medical Center after returning to the United States from Japan following an on-board outbreak of COVID-19. [19] Positive results were seen with remdesivir after use by the University of Washington in the first case of COVID-19 documented on US soil. [20] The drug was prescribed under an open-label Compassionate Use protocol, but the US FDA has since moved to allow Expanded access to remdesivir, permitting approved sites to prescribe the investigational product for multiple patients under protocol without requesting permission for each. [21] Remdesivir trials for moderate or severe COVID-19 compared with standard of care are ongoing. The first published report with a group of patients receiving remdesivir compassionate use described clinical improvement in 36 of 53 hospitalized patients (68%) with severe COVID-19. At baseline, 30 patients (57%) were receiving ventilation and 4 (8%) extracorporeal membrane oxygenation (ECMO). Measurement of efficacy requires randomized, placebo-controlled trials. [22]
