An editorial published in the New England Journal of Medicine has analysed a large-scale trial of Gilead’s antiviral COVID-19 drug remdesivir conducted by the World Health Organization (WHO).
The WHO’s Solidary trial aimed to determine the effect of remdesivir treatment on mortality in COVID-19 patients, finding in an interim analysis that the antiviral had no effect on in-hospital mortality.
In an editorial responding to the findings, written by David Harrington, Lindsey Baden and Joseph Hogan, the authors said that while the trial adds ‘important new information’, it is still ‘essential’ to consider the context of the randomised trial.
In particular, they wrote that ‘no intervention acts on two persons in an identical fashion: patients present with different risk factors, are treated in different healthcare settings, and begin treatment at different stages of illness’.
The Solidary trial also took place across a number of different countries including Canada, France and Switzerland, as well as Peru, the Philippines and South Africa.
The trial therefore collected information relating to the treatment from hospitalised patients who were receiving varied and ‘evolving’ standards of care.
Although the Solidary trial found no evidence of mortality reduction associated with remdesivir, Gilead’s own ACTT-1 trial found that the treatment plus standard-of-care cut the time to clinical recovery by five days compared to placebo.
‘Even without a reduction in in-hospital mortality, reducing the time to recovery and hospital discharge among patients who survive is important, both for patients and for stressed healthcare systems,’ wrote the NEJM authors.
In October, the US Food and Drug Administration (FDA) approved remdesivir under the brand name Veklury for the treatment of hospitalised COVID-19 patients, based on the ACTT-1 trial data.
In addition to the results from the ACTT-1 trial, the FDA approval was also supported by results from two phase 3 open-label studies of remdesivir, which evaluated the drug in adult patients with severe and moderate COVID-19.
The study, SIMPLE-Severe, found that a five- or ten-day course of remdesivir achieved similar outcomes in hospitalised patients who required supplemental oxygen but who were not mechanically ventilated.
Another study, SIMPLE-Moderate, showed statistically improved clinical outcomes with a five-day course of remdesivir compared to standard-of-care treatment in hospitalised patients who did not require supplemental oxygen.
The NEJM authors maintained that there are still questions revolving around administering remdesivir as a treatment for COVID-19.
‘Should remdesivir be reserved for the treatment of patients with selected risk factors? What is a more effective timing for the use of remdesivir, and should it be used in combination with other agents? How is the course of hospitalisation affected by the type and level of care delivered in particular settings?
“How to answer these more complicated and nuanced questions quickly remains a challenge for the scientific community. It will not be simple to achieve clarity on when and how — or even whether — to use remdesivir,’ the authors concluded.