麻豆传媒

Remdesivir (Veklury) reduced risk of hospitalizations by 87% compared with placebo in outpatients at high risk of progression to severe COVID-19, a researcher said.

While the raw numbers were small -- two in the remdesivir arm versus 15 in the placebo arm -- the remdesivir arm had a significantly lower risk of hospitalization (0.7% vs 5.3%, respectively; HR 0.13, 95% CI 0.03-0.59, P=0.008), reported Joshua Hill, MD, of Fred Hutchinson Cancer Research Center in Seattle, during a late-breaking presentation at virtual IDWeek.

That means 95% of patients did not progress to severe disease, he noted, suggesting that there might be subgroups, such as those with hematologic malignancies or transplant patients, who might benefit from the therapy.

"More precision studies, especially in high-risk populations, would be really helpful," added session moderator Adarsh Bhimraj, MD, of the Cleveland Clinic.

Remdesivir also reduced risk of COVID-related medically attended visits or all-cause death by day 28 -- a secondary outcome of the study -- by 81%. Again, the numbers were small: five in the remdesivir group versus 21 in the placebo group.

Adverse events (AEs) were comparable between the groups, with no new safety signals reported.

However, enrollment was halted due to the availability of single-infusion monoclonal antibodies and "increasing vaccine rates in the high-risk patient population," which were both exclusion criteria for the study, Hill said. While the goal of the trial was to enroll 1,264 patients, there were 584 randomized, and 562 who received at least one dose of the study drug.

The currently recommend remdesivir for patients who are hospitalized and on supplemental oxygen, as well as remdesivir plus dexamethasone for hospitalized patients requiring high-flow oxygen or non-invasive ventilation, but there is insufficient evidence for remdesivir in hospitalized patients who do not require supplemental oxygen.

Bhimraj, who was not involved with the research, commented that clinicians are "looking for new therapy in [COVID] patients who are not hospitalized."

"From decades of experience in the field of virology ... early initiation of antiviral treatment may be the most effective way to prevent disease progression, particularly for those who are at highest risk," Hill said.

He also pointed out that there are monoclonal antibody shortages and rationing in some parts of the country, as well as limited availability of monoclonal antibodies outside the U.S. He highlighted remdesivir's "distinct mechanism of action" which could be effective against variants of concern that escape monoclonal antibody treatments.

The phase III enrolled COVID outpatients and those in skilled nursing facilities, and included participants ages 12 and older who were at high risk for severe disease, as well as all adults ages 60 and up. Study enrollment started Sept. 18, 2020 and ended on April 8, 2021.

The primary outcome was a composite of COVID-19 hospitalization and all-cause death at day 28, as well as the proportion of patients with treatment-emergent AEs.

Hill noted that this was a shorter course of the drug (3 days vs the usual 5-day course), with patients receiving 200 mg IV on day 1, and 100 mg IV on days 2 and 3. Control participants received matching placebo.

Mean patient age was 50; 30% were 60 and older. Most were white, though Hill said that about 42%-46% identified as being of Hispanic ethnicity. Median body mass index was 30, and the most common comorbidities were obesity, diabetes, and hypertension. About 3% of participants received infusions at a skilled nursing facility.

Rates of AEs was similar in the remdesivir and placebo groups (42% vs 46%, respectively), most commonly nausea and headache. There was a higher rate of grade ≥3 AEs in the placebo group (4% vs 7%), which Hill said reflected a higher hospitalization rate. There was one grade 3 AE in the remdesivir group, an increase in transaminase levels, which resolved in about a week, he noted.

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