Drug shows promise in an unpublished trial, but no benefit in first peer-reviewed clinical trial

Despite conflicting data on the efficacy of the investigational drug remdesivir for the treatment of SARS-CoV-2, federal officials and the nation’s top infectious disease doctor enthusiastically endorsed it on Wednesday as a potentially game-changing treatment for the disease.

In an afternoon press briefing at the White House, flanked by President Donald Trump and Vice President Mike Pence, NIAID director Anthony Fauci, MD, touted preliminary findings from an as yet unpublished study of the Gilead Sciences drug and said remdesivir would be “the standard of care” for treatment of Covid-19.

Early results from the randomized clinical trial, summarized in a National Institutes of Health press release made public Wednesday, showed an earlier median time to recovery among patients treated with remdesivir compared to placebo — 11 days versus 15 days. The data also show a modest survival benefit in the patients receiving the broad-spectrum antiviral drug (8.0% death rate versus 11.6%).

“Although a 31% improvement doesn’t seem like a knock-out 100%, it is a very important proof of concept because what it has proven is that a drug can block this virus,” Fauci said.

Following Fauci’s remarks, press reports suggested that the U.S. Food and Drug Administration will soon announce emergency approval for use of the drug as a treatment for Covid-19, based on the early findings from the ongoing trial, which began in mid-February and involves 1,063 patients.

The agency “has been engaged in sustained and ongoing discussions with Gilead Sciences regarding making remdesivir available to patients as quickly as possible, as appropriate,” FDA media specialist Michael Felberbaum said in an email exchange with BreakingMED.

But just hours before Fauci made his Oval Office comments, peer-reviewed results from the first randomized trial of remdesivir in patients with Covid-19 were published in The Lancet, finding no clinical benefit associated with its use.

The trial, which included 237 hospitalized Covid-19 patients in Wuhan, China, showed no statistically significant difference in average time to clinical improvement between the remdesivir and placebo groups (21 days vs 23 days, respectively). And, death rates within 28 days of study randomization were also similar between the two groups, with 14% (22/158) of patients treated with remdesivir dying during this period, compared to 13% (10/78) placebo patients.

Patients treated with remdesivir within 10 days of Covid-19 symptom onset did have a lower incidence of death in a secondary analysis (11% vs 15%), but the difference was not statistically significant.

In an interview with BreakingMED, Society of Critical Care Medicine executive council member Sandra Kane-Gill, PharmD, said significant study limitations in the Wuhan study limit interpretation of the findings.

While the original study design called for recruitment of roughly 450 patients to achieve sufficient power, just 237 patients were enrolled before the trial was stopped early due to difficulty finding patients.

And, 54% of the enrolled patients were first treated with remdesivir 11 days or more after developing symptoms related to Covid-19.

“The sample size to meet the primary outcome was not sufficient, and they may have waited too long to treat these patients,” Kane-Gill said.

With regard to the U.S. study, Kane-Gill said it is not possible to know if the optimism is warranted without seeing actual study data.

“Hopefully, Dr. Fauci has seen all the data, so he is in a much better position to have an opinion about it than I am,” she said, adding that all she or anyone else in the public has seen is “three paragraphs in a (NIH) press release.”

“The study appears to be designed well, and interim analysis is positive,” she said. “Right now, there does not appear to be a mortality benefit, but all the patients are not enrolled yet.”

Her takeaway is that the study seems promising, based on Fauci’s comments about it.

“The difference between me and him is he knows more than I do,” she said.

In an editorial published with the Wuhan trial findings in The Lancet, John David Norrie, of the University of Edinburgh in Scotland, noted that it is not yet clear if remdesivir is beneficial or may do harm as a treatment of Covid-19, based on the clinical trials data reported to date.

He noted that the “unintended” early release of the Wuhan study findings on the website of the World Health Organization a week before their publication in the medical journal — and the interpretation that the drug failed its first trial — illustrate “the particular challenges of delivering pandemic trials” and the importance of “data sharing, allowing rapid curation of relevant datasets for individual patient data meta-analysis.

“With each individual study at heightened risk of being incomplete, pooling data across possibly several underpowered but high-quality studies looks like our best way to obtain robust insights into what works, safely and on whom. We eagerly await the ongoing trials,” he wrote.

  1. Early results from a randomized clinical trial, summarized in a National Institutes of Health press release made public Wednesday, showed an earlier median time to recovery among patients treated with remdesivir compared to placebo — 11 days versus 15 days.

  2. However, be aware that peer-reviewed results from the first randomized trial of remdesivir in patients with Covid-19 suggested little clinical benefit associated with its use.

Salynn Boyles, Contributing Writer, BreakingMED™

Funding for the Wuhan study was provided by the Chinese Academy of Medical Sciences Emergency Project of Covid-19, National Key Research and Development Program of China, and the Beijing Sciences and Technology Project.

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