Early Use of Remdesivir (Continued)

Two important communications turned up on my computer recently. First, two letters to the editor of The New England Journal of Medicine commenting on Beigel et al, Remdesivir for the Treatment of Covid-19 — Preliminary Report, published online on May 22 at NEJM.org. Both drew attention to the late introduction of remdesivir in the trial: the median time from symptom onset to randomization was 9 days. Then, an online message came from JAMA with an excellent review article (WJ Wiersinga et al. Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019), which states: “Although viral nucleic acid can be detectable in throat swabs for up to 6 weeks after the onset of illness, several studies suggest that viral cultures are generally negative for SARS-CoV-2 8 days after symptom onset.”

Back on May 3, the CDC had a relevant post on its web site: “At this time, replication-competent virus has not been successfully cultured more than 9 days after onset of illness. The statistically estimated likelihood of recovering replication-competent virus approaches zero by 10 days.”

Remdesivir’s mechanism of action is inhibition of viral replication. When the virus is no longer replicating, the drug cannot be effective. Given the timing of its administration in the Beigel study, it is impressive that even a shorter time to recovery was detectable in patients given the active drug and that the difference in mortality between remdesivir- and placebo-treated patients even came close to statistical significance (8% vs 11.6%, p=0.059).

None of the remdesivir clinical trials currently listed in ClinicalTrials.gov exclude patients who are more than 8, 9, or any other number of days past the onset of symptoms. Admittedly, early use of remdesivir presents some problems. For one, it is an unapproved drug and the FDA’s Federal Emergency Use Authorization specifies hospitalized patients with severe disease. For another, the current formulation must be given intravenously, which is complicated in outpatients. The good news is that the manufacturer (Gilead) has developed a new formulation that can be inhaled via a nebulizer. It is scheduled to begin Phase 1 trials immediately and Phase 2 in outpatient Covid-19 patients, possibly in nursing homes, in August.

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