More on Use of Remdesivir to Hasten Recovery for Severe COVID-19 Patients
A published report on preliminary results of a clinical trial of remdesivir in patients with severe COVID-19 and lower respiratory tract infection found the drug shortened recovery time but also cautions that treatment with an antiviral drug alone is not likely to be sufficient to lower high mortality rates. Here is more information.
BETHESDA, MD – A published study provides more information about the use of remdesivir to speed recovery for patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
The report in the New England Journal of Medicine concludes that the broad-spectrum antiviral medication developed by the biopharmaceutical company Gilead Sciences was superior to placebo in shortening the time to recovery in adults hospitalized with COVID-19 and who had evidence of lower respiratory tract infection.
National Institute of Allergy and Infectious Diseases researchers conducted the double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults with novel coronavirus. The 1,063 participants were randomly assigned to receive either remdesivir at 200 mg loading dose on day 1, followed by 100 mg daily for up to nine additional days, or placebo for up to 10 days. Defined as the primary outcome was the time to recovery, determined by either discharge from the hospital or hospitalization for infection-control purposes only.
The Food and Drug Administration has made remdesivir available under an emergency-use authorization for the treatment of adults and children with severe COVID-19 disease. Researchers emphasize that their preliminary report is intended to help inform clinicians considering the use of remdesivir, adding, “We are awaiting final visits, data entry, monitoring, and data lock for the last of the 1,063 patients enrolled, after which an update of the results will be provided.” The authors add that the efficacy of remdesivir in the trial won’t be fully understood until full statistical analysis of the entire trial population occurs.
“These preliminary findings support the use of remdesivir for patients who are hospitalized with COVID-19 and require supplemental oxygen therapy,” the study explains. “However, given high mortality despite the use of remdesivir, it is clear that treatment with an antiviral drug alone is not likely to be sufficient. Future strategies should evaluate antiviral agents in combination with other therapeutic approaches or combinations of antiviral agents to continue to improve patient outcomes in Covid-19.”
The data and safety monitoring board recommended early unblinding of the results on the basis of findings from an analysis that showed shortened time to recovery in the remdesivir group. Preliminary results from the 1059 patients -- 538 assigned to remdesivir and 521 to placebo -- with data available after randomization indicate that those who received remdesivir had a median recovery time of 11 days (95% confidence interval [CI], 9 to 12), vs. 15 days (95% CI, 13 to 19) in those who received placebo (rate ratio for recovery, 1.32; 95% CI, 1.12 to 1.55; P<0.001).
Researchers report that the Kaplan-Meier estimates of mortality by 14 days were 7.1% with remdesivir and 11.9% with placebo (hazard ratio for death, 0.70; 95% CI, 0.47 to 1.04). Serious adverse events were reported for 114 of the 541 patients in the remdesivir group who underwent randomization (21.1%), and 141 of the 522 patients in the placebo group who underwent randomization (27.0%).
The authors explain that remdesivir (GS-5734), an inhibitor of the viral RNA-dependent, RNA polymerase with inhibitory activity against Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), was targeted as a promising therapeutic candidate for COVID-19 because of its ability to inhibit SARS-CoV-2 in vitro. They also note that remdesivir initiated 12 hours after inoculation with MERS-CoV in non-human primate studies reduced lung virus levels and lung damage.
The study was the first stage of the Adaptive Covid-19 Treatment Trial (ACTT-1), in which researchers evaluated treatment with remdesivir as compared with placebo. Now, another study has been launched evaluating a treatment regimen of that investigational antiviral combined with the anti-inflammatory drug baricitinib.
Baricitinib, marketed as Olumiant, is licensed to Eli Lilly and Company by Incyte and is approved in the United States and more than 65 additional countries as a treatment for adults with moderately to severely active rheumatoid arthritis.