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Remdesivir (Veklury) reduced serious outcomes among unvaccinated high-risk COVID-19 patients when given during the early symptomatic period outside the hospital, as published results from the trial detailed.

A 3-day course of the IV antiviral cut hospitalization for COVID-19 or death from any cause by a relative 87%, albeit based on just two cases versus 15 among placebo-treated patients (0.7% vs 5.3%, P=0.008), reported Robert Gottlieb, MD, PhD, of Baylor University Medical Center in Dallas, and colleagues.

Other healthcare visits also appeared to be prevented, with a similar reduction in the composite of overall COVID-related medically attended visits or death (four vs 21 cases, 1.6% vs 8.3%, HR 0.19, 95% CI 0.07-0.56). No deaths occurred in either treatment group.

These findings, published in the , mirror what had been initially announced in a late-breaking presentation at the virtual IDWeek meeting in October.

"In the campaign toward ending the COVID-19 pandemic, these data add yet another option to the armamentarium for the treatment of vulnerable patients who are at high risk for progression to severe COVID-19," the researchers concluded.

They suggested that there is still need for such treatments in regions of the world that do not yet have vaccine access and for the immunocompromised who don't get a good vaccine response.

And indeed, "these results equate to a difference of 47 fewer hospitalizations per 1,000 infections, a clinically significant finding in an overwhelmed health care system," noted an by Emily Heil, PharmD, and Shyam Kottilil, MD, PhD, of the University of Maryland Schools of Pharmacy and Medicine, respectively, in Baltimore.

Even for vaccinated patients, antiviral agents could provide an important weapon against new variants, Heil and Kottilil added.

"Rapid emergence of variants with adaptive mutations in the spike protein can result in escape from vaccines and monoclonal antibodies, whereas antiviral agents, given the absence of variation in their viral target, are likely to maintain activity, reinforcing the value of antivirals such as remdesivir in curtailing the pandemic," the editorialists wrote.

Remdesivir joins a number of other agents that have shown efficacy in mild-to-moderate COVID-19, including antivirals molnupiravir and nirmatrelvir-ritonavir (Paxlovid) and neutralizing monoclonal antibodies bamlanivimab-etesevimab, casirivimab-imdevimab, and sotrovimab.

However, there were a number of concerns raised about the findings from the phase III PINETREE trial, which had been stopped early in the context of declining infections and increasing vaccination rates after randomization of 562 patients out of a planned 1,264 (44.5%).

The trial findings were based on small numbers of events and before the emergence of the Delta or Omicron variants.

As the study enrolled only unvaccinated patients with confirmed SARS-CoV-2 infection and at least one risk factor for progression to severe disease or age 60 or older, questions of how remdesivir would do for breakthrough infection in the vaccinated remain unanswered.

Then there is the practical issue of administering an intravenous drug to outpatients, Heil and Kottilil noted.

In the trial, patients were randomized to remdesivir within 7 days of symptom onset largely at outpatient infusion facilities and skilled nursing facilities, although some also received their infusions at home.

"Access to and uptake of single-dose monoclonal antibodies have been challenging, a fact that does not bode well for a 3-day course of outpatient intravenous remdesivir," the editorialists wrote.

"Although remdesivir administration requires less monitoring than monoclonal antibody administration," for most patients it would mean multiple health care interactions during acute infection, they added. "Agents that could be administrated orally would be vastly easier to implement in the outpatient setting."

The researchers pointed out that remdesivir does have an advantage in being able to be shipped and stored lyophilized at room temperature. Also, "this trial provides a proof of concept for the study of new prodrugs of the active metabolite of remdesivir," which would be oral agents, the team added.

Another concern was that the trial didn't show any greater reduction in viral load, determined with the use of nasopharyngeal swabs, from baseline to day 7 in the remdesivir group compared with placebo.

"So the question arises of whether remdesivir would in fact reduce transmissibility in infected persons (an important consideration in outpatient therapeutics) as compared with monoclonal antibodies or new oral antiviral agents, which are both associated with a more rapid decline in viral burden than placebo," Heil and Kottilil wrote.

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