Gilead shares compassionate use data for remdesivir in patients with COVID-19 and a new research paper suggests remdesivir's mechanism of action could make it effective in combatting the virus.
New data of remdesivir for the novel coronavirus disease (COVID-19) through its compassionate use program showed clinical improvement in the majority of patients treated with the experimental therapy who were analyzed, according an analysis published in The New England Journal of Medicine.1
Meanwhile, a new paper examining the mechanisms of remdesivir’s actions reinforces the promise of clinical trials for the drug in patients with COVID-19.2
However, data are still limited and will require future controlled clinical trials to better determine remdesivir’s use as a treatment for COVID-19.
Remdesivir was provided on a compassionate-use basis to patients hospitalized with COVID-19, the illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients in the analysis had confirmed SARS-CoV-2 infection and an oxygen saturation of 94% or less while they were breathing ambient air or were receiving oxygen support.1
During treatment, patients received a 10-day course of remdesivir, consisting of 200 mg administered intravenously on day 1, followed by 100 mg daily for the remaining 9 days of treatment.1
Of the 61 patients who received at least 1 dose of remdesivir, data from 8 could not be analyzed. Of the 52 patients whose data were analyzed, 57% were receiving mechanical ventilaton and 8% were receiving extracorporeal membrane oxygenation. During a median follow-up of 18 days, 68% of patients had an improvement in oxygen-support class, including 17 of the patients who were receiving mechanical ventilation who were extubated. Overall, 47% of patients were discharged and 13% died, with a mortality of 18% among those receiving invasive ventilation and 5% among those who did not receive invasive ventilation, according to the findings.1
The study results determined that clinical improvement was observed in a total of 68% of patients who were treated with remdesivir, according to the data.1
“Currently, there is no proven treatment for COVID-19. We cannot draw definitive conclusions from these data, but the observations from this group of hospitalized patients who received remdesivir are hopeful,” lead study author Jonathan D. Grein, MD, Director of Hospital Epidemiology, Cedars-Sinai Medical Center, Los Angeles, said in a statement.3 “We look forward to the results of controlled clinical trials to potentially validate these findings.”
Moreover, the compassionate use program did not collect viral load data to confirm the antiviral effects of remdesivir or any association between baseline viral load and viral suppression and clinical response, according to the study. No new safety signals were detected during short-term remdesivir therapy in this cohort.1
A recent study, published in the Journal of Biological Chemistry, analyzed how remdesivir works, suggesting that the experimental therapy may be effective against a key enzyme of SARS-CoV-2.2
Replication of SARS-CoV-2 depends on the viral RNA-dependent RNA polymerase (RdRp), which is the likely target of the investigational nucleotide analogue remdesivir, according to the study authors. Remdesivir has shown broad-spectrum-antiviral activity against RNA viruses. In previous studies with RdRps from Ebola virus and Middle East respiratory syndrome coronavirus (MERS-CoV), delayed chain-termination has been shown as remdesivir’s plausible mechanism of action, the authors wrote.2
“We obtained almost identical results as we reported previously with MERS, so we see that remdesivir is a very potent inhibitor for coronavirus polymerases,” Matthias GÃ¶tte, MD, chair of medical microbiology and immunology at the University of Alberta, who is the lead author of the paper, said in a press release.4
Although the findings are promising, Dr GÃ¶tte noted that the results obtained in the lab cannot be used to predict how the drug will work in humans.4
“We’ve got to be patient and wait for the results of the randomized clinical trials,” GÃ¶tte said.4
The research was funded by the Canadian Institutes of Health Research, Alberta’s Major Innovation Fund, and Gilead Sciences.
1. Grein J, Ohmagari N, Shin D, et al. Compassionate use of remdesivir for patients with severe covid-19. New England Journal of Medicine. April 10, 2020. Doi: 10.1056/NEJMoa2007016
2. Gordon CJ, Tchesnokov EP, Woolner E. Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA-polymerase from severe acute respiratory syndrome coronavirus 2 with high potency. Journal of Biological Chemistry. April 13, 2020. Doi: 10.1074/jbc.RA120.013679
3. Data on 53 Patients Treated With Investigational Antiviral Remdesivir Through the Compassionate Use Program Published in New England Journal of Medicine. News Release. Gilead Sciences; April 10, 2020. https://www.gilead.com/news-and-press/press-room/press-releases/2020/4/data-on-53-patients-treated-with-investigational-antiviral-remdesivir-through-the-compassionate-use-program-published-in-new-england-journal-of-medici. Accessed April 14, 2020.
4. U of A virology lab finds drug originally meant for Ebola is effective against a key enzyme of coronavirus that causes COVID-19. News Release; April 13, 2020. https://www.folio.ca/u-of-a-virology-lab-finds-drug-originally-meant-for-ebola-is-effective-against-a-key-enzyme-of-coronavirus-that-causes-covid-19/. Accessed April 14, 2020.