Remdesivir in Treatment of COVID-19: A Systematic Benefit–Risk Assessment

Abstract

Introduction There is a need to identify effective, safe treatments for COVID-19 (coronavirus disease) rapidly, given the current, ongoing pandemic. A systematic benefit-risk assessment was designed and conducted to examine the benefit-risk profile of remdesivir in COVID-19 patients compared with standard of care, placebo or other treatments. A key objective of this study was to provide a platform for a dynamic systematic benefit-risk evaluation, which starts with inevitably limited information (to meet the urgent unmet public health need worldwide), then update the benefit-risk evaluation as more data become available. Methods The Benefit-Risk Action Team (BRAT) framework was used to assess the overall benefit-risk of the use of remdesivir as a treatment for COVID-19 compared with standard of care, placebo or other treatments. We searched PubMed, Google Scholar and government agency websites to identify literature reporting clinical outcomes in patients taking remdesivir for COVID-19. A value tree was constructed and key benefits and risks were ranked by two clinicians in order of considered importance. Results Using the BRAT method, several key benefits and risks for use of remdesivir in COVID-19 compared with placebo have been identified. In one trial, the benefit of time to clinical improvement was not statistically significant (21 vs 23 days, HR 1.23, 95% CI 0.87-1.75), although the study was underpowered. In another trial, a shorter time to recovery in patients treated with remdesivir was observed (11 vs 15 days), with non-significant reduced mortality risk (8% vs 12%). Risk data were only available from one trial. This trial reported fewer serious adverse events in patients taking remdesivir (18%) compared with the placebo group (26%); however, more patients in the remdesivir group discontinued treatment as a result of an adverse event compared with those patients receiving placebo (12% vs 5%). Conclusions Preliminary clinical trial results suggest that there may be a favourable benefit-risk profile for remdesivir compared with placebo in severe COVID-19 infection and further data on benefits would strengthen this evaluation. There is limited safety data for remdesivir, which should be obtained in further studies. The current framework summarises the key anticipated benefits and risks for which further data are needed. Ongoing clinical trial data can be incorporated into the framework when available to provide an updated benefit-risk assessment.

Pirfenidone: A novel hypothetical treatment for COVID-19

“…A large number of suggested treatments such as ivermectin, hydroxychloroquine, and azithromycin are currently under investigation. Among them, hydroxychloroquine, azithromycin, and recently remdesivir showed acceptable results in clinical trials, as of June 2020 [4][5][6][7][8][9][10]. Nevertheless, the results of these interventions are not completely satisfactory and studies for other medications are still warranted .…”

Mechanisms Underlying Potential Therapeutic Approaches for COVID-19

“…Recently, Yeming et al published the results of the NCT04257656 clinical trial, which showed no clear outcome because of the death or discharge of patients ( 73 ). Moreover, in another clinical trial, the benefit in terms of the time to clinical improvement was not statistically significant (21 vs. 23 days), even though the study was underpowered ( 74 ). There are limited safety data for remdesivir, which should be obtained in further studies.…”

Potential Therapeutic Options for COVID-19: Current Status, Challenges, and Future Perspectives

“…Based on the current pandemic, a report has recently been demonstrated an adaptive, randomized, placebo-controlled, double blind phase 3 (NCT04257656) clinical trial to evaluate the efficacy and safety of this drug (200 mg on day 1 and 100 mg once daily for 9 days) combined with the supportive care in the hospitalized 237 COVID-19 patients (Scavone et al, 2020;Wang et al, 2020b). But this initial studies with remdesivir showed no benefit as underpowered (Davies et al, 2020;Wang et al, 2020a), this changed with the NIH study called COVID-19 Adaptive Treatment Trial (ACTT 3) in which the safety and efficacy of a treatment regimen consisting of remdesivir plus the interferon beta-1a immunomodulator in patients with coronavirus 2019 (COVID-19) will be evaluated (National Institutes of Health, 2020). Remdesivir has recently been granted a conditional marketing authorization in the European Union countries by the European Commission (Agency, 2020).…”

“…But this initial studies with remdesivir showed no benefit as underpowered ( Davies et al., 2020 ; Wang et al., 2020a ), this changed with the NIH study called COVID-19 Adaptive Treatment Trial (ACTT 3) in which the safety and efficacy of a treatment regimen consisting of remdesivir plus the interferon beta-1a immunomodulator in patients with coronavirus 2019 (COVID-19) will be evaluated ( National Institutes of Health, 2020 ). Remdesivir has recently been granted a conditional marketing authorization in the European Union countries by the European Commission ( Agency, 2020 ).…”