3-day remdesivir prevents hospitalization, death in COVID-19
A 3-day course of remdesivir may help stave off COVID-19–related hospitalization and death, according to results of the phase III PINETREE study.
Participants in this multinational, double-blind trial were 562 high-risk patients* (mean age ~50 years [30 percent aged ≥60 years], 52 percent male, median BMI 30.7 kg/m2) with confirmed COVID-19** who were not admitted to hospital. They were randomized 1:1 to receive intravenous remdesivir (200 mg on day 1, 100 mg on days 2–3) or placebo for 3 days.
The SARS-CoV-2 RNA nasopharyngeal viral load at baseline was a median 6.2 log10 copies/mL and patients had experienced symptoms for a median 5 days before the first dose of drug. The most common comorbidities in the population were diabetes, obesity, and hypertension, at 62, 56, and 48 percent, respectively.
At day 28, there was an 87 percent reduction in the risk of a composite of COVID-19–related hospitalization or all-cause death with remdesivir vs placebo (0.7 percent vs 5.3 percent; hazard ratio [HR], 0.13, 95 percent confidence interval [CI], 0.03–0.59; p=0.008). [ID Week 2021, abstract LB1]
The between-group difference was evident from day 2, as noted by the separation of the curves, and was maintained to day 28, said Assistant Professor Joshua Hill from the Fred Hutchinson Cancer Research Center in Seattle, Washington, US, who presented the results at ID Week.
The risk of COVID-19–related medically attended visits or all-cause death at day 28 was also reduced by 81 percent with remdesivir compared with placebo (1.6 percent vs 8.3 percent; HR, 0.19, 95 percent CI, 0.07–0.56; p=0.002).
The time-weighted average change in SARS-CoV-2 nasopharyngeal viral loads between baseline and day 7 did not differ between the remdesivir and placebo groups (median -1.15 vs -1.11 log10 copies/mL; least-squares mean difference, 0.07; p=0.43).
Treatment-emergent adverse event (TEAE) rates were similar between the remdesivir and placebo groups (42.3 percent vs 46.3 percent). Grade ≥3 TEAEs occurred in 3.6 and 7.1 percent of the remdesivir and placebo groups, respectively, and serious TEAEs in 1.8 and 6.7 percent, respectively. None of the serious AEs were deemed related to study drug and the higher number of serious AEs in the placebo group was reflective of the higher hospitalization rate in this group. One remdesivir recipient experienced a grade ≥3 study drug-related TEAE (elevated transaminase levels).
The most frequently occurring AEs in remdesivir recipients were nausea, headache, and diarrhoea (11, 6, and 4 percent, respectively). There were no deaths in either the remdesivir or placebo group at day 28.
“We still have very few treatment options to offer people who develop COVID-19, are at increased risk for progression, but are not yet hospitalized or not requiring hospitalization,” said Hill.
“What we know from decades of experience in the field of virology [is that] early initiation of antiviral treatment may be the most effective way to prevent disease progression, particularly for those who are at highest risk,” he continued.
“Remdesivir for 3 days provides a safe and highly effective treatment for non-hospitalized patients with COVID-19 at high risk for progression,” said Hill.
As there were no deaths, the benefits with remdesivir were specific to COVID-19–related hospitalizations or medically attended visits, he said.
Hill also noted that the lack of difference between groups pertaining to SARS-CoV-2 nasopharyngeal viral load, despite the improvement in clinical outcomes, suggests that upper respiratory viral load is an inadequate surrogate for efficacy of remdesivir.