A study published late last week in the New England Journal of Medicine found that hospitalized COVID-19 patients who received Gilead Sciences' antiviral drug remdesivir recovered a median of 4 days earlier than those who received a placebo.
Preliminary findings from the double-blind Adaptive COVID-19 Treatment Trial (ACTT-1), sponsored by the US National Institute of Allergy and Infectious Diseases (NIAID), showed that the 538 patients randomly assigned to receive remdesivir had a median recovery time of 11 days (95% confidence interval [CI], 9 to 12), compared with 15 days (95% CI, 13 to 19) in the 521 patients who received a placebo (rate ratio for recovery, 1.32; 95% CI, 1.12 to 1.55; P < 0.001).
The patients were enrolled from Feb 21 to Apr 19 at 60 study sites and 13 subsites in the United States and Mexico (79.8%), Europe (15.3%), and Asia (4.9%), on the basis of the evolving epidemiology of the pandemic.
Patients received either a placebo for 10 days or remdesivir intravenously as a 200-milligram (mg) loading dose followed by 100-mg maintenance doses for the next 9 days or until release from the hospital or death. The analysis includes only patients with at least some post-baseline data available.
Importance of starting the drug early
The most common disease severity score, rated from 1 (not requiring hospitalization) to 8 (dead), was 5 (needing oxygen). In patients with a score of 5, remdesivir was associated with a 47% speedier recovery, versus 20% in patients with a score of 6 (needing high-flow ventilation), and only 0.05% in patients with a score of 7 (needing intubation or extracorporeal membrane oxygenation [oxygen added to the blood outside the body]).
The authors noted that patients requiring supplemental oxygen derived the most benefit from remdesivir, while it did not benefit those requiring more intense treatments. "Our findings highlight the need to identify COVID-19 cases and start antiviral treatment before the pulmonary disease progresses to require mechanical ventilation," they wrote.
Differences in Kaplan-Meier estimates of death by 14 days were not significantly different between the two groups, at 7.1% in the remdesivir group and 11.9% in the placebo group (hazard ratio for death, 0.70; 95% CI, 0.47 to 1.04).
Serious adverse events occurred in 114 of 541 patients (21.1%) receiving remdesivir and 141 of the 522 patients (27.0%) receiving placebo. The investigators determined that 2 events each were due to remdesivir and placebo. No treatment-related deaths were reported.
Twenty-eight patients (5.2%) in the remdesivir group had acute respiratory adverse events, compared with 42 (8.0%) in the placebo group. The placebo group had slightly higher rates of acute respiratory failure, low blood pressure, pneumonia, and acute kidney injury than did the remdesivir group.
Kaplan-Meier estimates of death by 28 days weren't reported in this analysis because of the large number of patients who hadn't yet had their day-29 visits.
Mean patient age was 58.9 years, and 64.3% were men. Overall, 53.2% of patients were white, 23.4% were Hispanic or Latino, 20.6% were black, 12.6% were Asian, and race/ethnicity in 13.6% was either unreported or characterized as "other."
Most patients had one (27.0%) or two or more (52.1%) underlying illnesses, the most common of which were high blood pressure (49.6%), obesity (37.0%), and type 2 diabetes (29.7%).
Median number of days between symptom onset and random assignment was 9. Overall, 943 patients (88.7%) had severe illness at study enrollment. No substantial differences in baseline characteristics were identified between patients receiving remdesivir and those receiving placebo.
Antiviral drugs alone likely insufficient
As of Apr 22, 482 patients had recovered, and 81 deaths had died. The study's data and safety monitoring board recommended that the preliminary results be unblinded early and reported to NIAID because of the promising results.
After the NIAID made the results public late last month, the US Food and Drug Administration on May 1 issued an emergency use authorization for remdesivir for the treatment of seriously ill COVID-19 patients.
At the time, NIAID Director Anthony Fauci, MD, said, "Although a 31% improvement doesn't seem like a knockout 100%, it is a very important proof of concept. Because what it has proven is that a drug can block this virus."
As of Apr 28, according to the now peer-reviewed data, 391 patients who received remdesivir and 340 who received placebo had completed the trial through day 29, recovered, or died. The authors said they will publish an update after they receive final data from the last enrolled patients.
The authors called for the evaluation of antiviral drugs in combination with other treatments or combinations of antiviral drugs to improve coronavirus patient outcomes.
"These preliminary findings support the use of remdesivir for patients who are hospitalized with COVID-19 and require supplemental oxygen therapy," they said. "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."
