In the landmark ACTT-1 clinical trial run by the National Institutes of Health, Gilead Sciences’ remdesivir was found to cut recovery time for hospitalized COVID-19 patients by four days. But the benefit was mainly confined to those requiring some oxygen support. Those who weren't quite so ill didn't get much of a boost.
In a new randomized clinical trial, the antiviral once again showed mixed results in moderately ill patients, raising questions as to whether it’s worthy of a full FDA nod for that group.
Remdesivir, when used as a 5-day treatment, had significantly better odds of helping moderate COVID-19 patients achieve better clinical status compared with standard therapy, according to data published Friday by JAMA. Surprisingly, though, a 10-day course of the drug failed to beat standard of care.
The results came in contrast to an earlier Gilead-sponsored phase 3 Simple study, which showed that moderately ill patients who did not require mechanical ventilation experienced similar clinical benefits whether they received the 5-day or the 10-day course of remdesivir.
The drug currently has an FDA emergency use authorization to treat severe COVID-19, and earlier this month Gilead submitted a new drug application seeking full approval in all hospitalized patients. It’s also conditionally approved, under the brand Veklury, in the EU only to treat patients who require supplemental oxygen.
Will Gilead’s all-comer plan for remdesivir in the U.S. come to fruition based on the current confusing results? It’s complicated.
First, as the authors of the JAMA paper pointed out, it’s unclear whether the improvement in clinical status—measured on a 7-point ordinal scale ranging from hospital discharge to death—was of clinical importance as it’s not as black-and-white a measure as patient death rate.
In a JAMA editorial that runs alongside the study, two University of Pittsburgh scientists noticed that not each step on the ordinal scale—which is endorsed by the World Health Organization—is of equal clinical significance. “[I]t is difficult to translate a summary odds ratio into a clinically meaningful statement for patients, clinicians, and policy makers,” they wrote.
Gilead Sciences' head of clinical research in HIV and emerging viruses, Diana Brainard, also told Reuters that the clinical importance of the benefit was uncertain, due to questions about how best to measure patient outcomes besides survival.
In a statement to FiercePharma, Brainard stressed that “the results from the NIAID clinical trials and Simple studies support the efficacy and safety profile of remdesivir across a range of hospitalized patients and were submitted to FDA as part of the NDA for remdesivir.”
To further complicate the current analysis, the 5-day and 10-day group assignments didn't necessarily translate into five and 10 days of actual treatment. In reality, only 76% of patients randomized to the 5-day course completed therapy; 35 patients (18%) fully recovered before they finished treatment.
In comparison, of the 193 patients in the 10-day group, only 38% completed the full course; 98 patients (51%) were discharged from the hospital before 10 days of treatment. The median number of treatment days was six.
The small proportion of patients treated for a full 10 days “further confounds any attempt to disentangle whether differences in outcome could be due to duration of therapy,” according to the editorial.
What’s more, there were no significant differences between either remdesivir group and standard care for some exploratory endpoints, such as duration of hospitalization or time to at least one point of clinical status improvement.
Despite the current findings and Gilead’s previous trial, the JAMA editorial still said the most suitable patient population for remdesivir remains unclear, as well as its optimal duration.
Editor's Note: The story has been updated with additional comment from Gilead's Diana Brainard.