Readout for Gilead’s remdesivir in COVID-19 could warrant emergency use authorization

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Remdesivir is the new standard of care for COVID-19, NIAID director Anthony Fauci said Wednesday. Other treatments will be compared with Gilead’s antiviral, and the therapy will be combined with other investigational drugs including anti-inflammatory mAbs.

An Emergency Use Authorization from FDA to treat COVID-19 could be the next step for the Gilead Sciences Inc. (NASDAQ:GILD) antiviral, according to former FDA Commissioner Scott Gottlieb.

“Remdesivir is not a perfect drug and is likely to be used in narrow circumstances, probably for patients who require hospitalization and are at risk of bad outcomes because of other co-morbidities,” Gottlieb told BioCentury. “This is a first generation antiviral. There are plenty of settings where first generation antiviral drugs have been eclipsed by subsequent approvals and I would expect the same thing to happen here.”

Fauci said preliminary data from the randomized, controlled Phase III ACTT study in severe COVID-19 patients showed that remdesivir "has a clear-cut significant positive effect in diminishing the time to recovery,” the primary endpoint, vs. placebo (11 vs. 15 days, p=0.001).

“This is a first generation antiviral. There are plenty of settings where first generation antiviral drugs have been eclipsed by subsequent approvals.”

Scott Gottlieb

ACTT was one of three remdesivir trials to read out Wednesday (see Daily Chart)

NIH’s National Institute of Allergy and Infectious Diseases sponsored the study, which enrolled about 800 patients.

“The NIH study is the first adequately powered and designed study for remdesivir,” Luciana Borio, VP at In-Q-Tel Inc. and former FDA acting chief scientist, told BioCentury. “It shows how important it is to conduct proper clinical trials to give us clear answers about the risks and benefits of promising drugs.”

The ACTT data also revealed a trend toward a survival benefit. The mortality rate in the remdesivir cohort was 8% vs. 11.6% for placebo (p=0.059). Fauci said that while the differences haven’t reached statistical significance yet, the data need to be further analyzed.

“The reported mortality in the control group is lower than many had expected,” Borio said. “Again, it shows the importance of supportive medical care to improve patients’ outcomes. We need to continue to search for additional therapeutic options for patients with more advanced disease,” said Borio.

Fauci announced the news a few hours after Gilead issued a release stating it is “aware of positive data” from NIAID’s adaptive, placebo-controlled Phase III study. The company did not disclose any specific data.

The readout “would appear to meet or exceed standard for authorization under EUA, especially relative to other EUAs issued,” Gottlieb wrote in a morning tweet. “The data from NIAID study should push this firmly over the line,” he also tweeted.

“It shows how important it is to conduct proper clinical trials to give us clear answers about the risks and benefits of promising drugs.”

Luciana Borio, In-Q-Tel

At a White House briefing, President Donald Trump said, “We would like to see very quick approvals, especially with things that work.” The president’s comment came in response to a reporter’s question as to whether he wants to see an EUA for Gilead’s therapy.

The news helped push Gilead’s shares up $4.47 to $83.14 Wednesday, adding more than $5.6 billion to the company’s market cap. On April 23, Gilead lost about $4.5 billion in market cap after data were published accidentally on the World Health Organization’s website showing that remdesivir’s use was not associated with clinical or virological benefits. Those data, from a study in China sponsored by Capital Medical University, were later removed from the website (see “First Glimpse Casts Doubt”).

Borio criticized the way data for the antiviral have been communicated.

“Rapid data analyses and communication of results is paramount for studies like these, but haphazard release of information is extremely unhelpful and confusing to the public and the medical community,” she said.

Later on Wednesday, an analysis of the placebo-controlled, Capital Medical University-sponsored study published in The Lancet concluded that remdesivir was “not associated with statistically significant clinical benefits,” although it said non-significant, numerical improvements in time to improvement warranted further study among patients receiving the therapy early in the disease’s course.

Borio tweeted that unlike ACTT, the Chinese study hadn’t been powered to detect modest benefit.

A new primary endpoint

Gilead also released data from its open-label Phase III SIMPLE trial in severe COVID-19 patients early Wednesday.

The company said remdesivir led to “similar improvements in clinical status” among treatment groups receiving five-day or 10-day courses of remdesivir plus standard of care. On the primary endpoint, 65% of patients treated for five days had a ≥2-point clinical improvement on a 7-point scale on day 14 vs. 54% of patients treated for 10 days (odds ratio=0.75, 95% CI: 0.51,1.12).

The odds ratio analysis wasn’t the original primary endpoint. A Gilead spokesperson told BioCentury it had been changed from clinical recovery -- normalization of fever and oxygen saturation through day 14 -- because the “scale is being used in multiple COVID-19 clinical trials worldwide and provides more granularity to assess the clinical efficacy. The current primary endpoint answers an important question about the length of treatment required for remdesivir for COVID-19.”

After 14 days, 64.5% of severe COVID-19 patients receiving five-day courses and 53.8% receiving 10-day courses were in clinical recovery. The groups included a total of 397 evaluable, hospitalized patients with severe disease.

The Gilead and the Capital Medical study results point to a need to tailor COVID-19 treatments to disease timing or severity. Subgroup analyses for both trials found better patient outcomes if remdesivir treatment began within 10 days of symptom onset (see “COVID-19: Closing in on Matching Therapeutic Mechanism to Disease Stage”).

Data are due late next month from 600 patients in another SIMPLE trial evaluating remdesivir’s effects in moderate COVID-19.

Remdesivir, a nucleotide analog, was developed initially as a treatment for Ebola.

-Washington Editor Steve Usdin contributed to this report.

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