In the first clinical study in the U.S. of a therapeutic targeting SARS-CoV-2, the National Institute of Allergy and Infectious Disease (NIAID) of the NIH released preliminary data yesterday showing that Gilead Sciences’ drug candidate remdesivir outperformed placebo in treating COVID-19 in hospitalized patients.
NIAID’s preliminary data demonstrated that the study met its primary outcome of statistically significant improvement in time to recovery by Day 29. Patients who were treated with remdesivir showed a median time to recovery of 11 days compared with 15 days for those who received placebo—a 31% faster time to recovery.
“Although a 31% improvement doesn’t seem like a knockout 100%, it is a very important proof of concept. What it has proven is that a drug can block this virus,” NIAID Director Anthony S. Fauci, MD, said today during an appearance with President Donald Trump. “This will be the standard of care.”
Trump added: “It’s a beginning. That means you build on it. But it’s a very positive event.”
Fauci said additional data will be released, while a study detailing the results will be submitted for publication in a peer-reviewed journal.
Remdesivir is among 18 candidates designated as “Front Runners” among 160+ COVID-19 therapeutics under study in GEN’s updated A-List published April 13, “Vanquishing the Virus: 160+ COVID-19 Drug and Vaccine Candidates in Development.”
NIAID: Survival benefit suggested
The preliminary findings also showed a mortality rate of 8.0% for the patient cohort treated with remdesivir, vs. 11.6% for the placebo group, a difference that according to NIAID suggested a survival benefit to the Gilead nucleotide prodrug.
The NIAID-sponsored Adaptive COVID-19 Treatment Trial (ACTT; NCT04280705) is an adaptive, randomized, double-blind, placebo-controlled trial that is evaluating 1,063 hospitalized adult patients with a broad mix of COVID-19 symptoms.
The trial—which concluded patient enrollment on April 19—is one of three randomized, blinded Phase III studies assessing the drug. Earlier this month, Gilead dramatically increased the patient populations of the study from an initial 440 patients, as well as its two other Phase III trials of remdesivir—from 400 to 2,400 patients in a study of adults with severe COVID-19 (NCT04292899), and from 600 to 1,600 moderate COVID-19 patients in the other study (NCT04292730).
Release of the preliminary results followed a meeting of the trial’s independent data and safety monitoring board, which shared its interim analysis of the findings with the team of researchers carrying out the trial.
“Based upon their review of the data, they noted that remdesivir was better than placebo from the perspective of the primary endpoint, time to recovery,” NIAID stated. “Recovery in this study was defined as being well enough for hospital discharge or returning to normal activity level.”
The first participating patient in the ACTT trial was an American who was repatriated after being quarantined on the Diamond Princess cruise ship that docked in Yokohama, Japan, and volunteered to participate in the study at the first study site, the University of Nebraska Medical Center/Nebraska Medicine, in February.
A total of 68 sites ultimately joined the study—47 in the U.S. and 21 in countries in Europe and Asia, NIAID said.
Based on the study results, the FDA was expected to announce it will grant an emergency use authorization (EUA) allowing use of remdesivir in patients, The New York Times reported, attributing the information to an unnamed “senior administration official.”
Advocating for the FDA to grant EUA status to the drug is its former commissioner, Scott Gottlieb, MD, now a resident fellow with the American Enterprise Institute and a partner with the venture investment firm NEA.
In a tweet posted 9:09 a.m. ET, Gottlieb wrote: “Accumulating data on Remdesivir suggests it’s active against COVID and there’s now enough data to support consideration of access under an emergency use authorization by FDA. The data from NIAID study should push this firmly over the line.
STAT senior writer Adam Feuerstein was even more positive in a tweet posted 8:49 a.m. ET, after Gilead first acknowledged positive data from the NIAID study, while deferring details to the agency to announce.
“Today, the world gets the first real sign that a new medicine, remdesivir from Gilead Sciences, will help the world emerge from the COVID-19 pandemic,” Feuerstein tweeted. “Pretty awesome.”
However, Eric Topol, MD, director of the Scripps Research Translational Institute, cautioned in a tweet posted 12:50 p.m. ET that the preliminary data from the NIAID trial “does not show statistically significant reduction in mortality (8% vs 11%, in the right direction) but a clear-cut benefit in time to recovery 11 vs 15 days.”
Chinese study results
The NIAID study was one of two remdesivir studies for which data was released today.
Earlier in the day, The Lancet published results showing that Gilead Sciences’ closely watched COVID-19 candidate remdesivir failed to show clinical improvement in severely infected patients in a Chinese Phase III trial (NCT04257656). In that study, Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial, remdesivir had not reduced the presence of SARS-CoV-2 in the bloodstream of 158 patients treated with the antiviral candidate in the 237-patient trial.
The primary endpoint was time to clinical improvement up to day 28, defined as the time (in days) from randomization to the point of a decline of two levels on a six-point ordinal scale of clinical status (from 1=discharged to 6=death) or discharged alive from hospital, whichever came first.
The average time to clinical improvement 21 days for patients in the remdesivir group, compared with 23 days in the placebo group.
“However, the numerical reduction in time to clinical improvement in those treated earlier requires confirmation in larger studies,” the authors of the study wrote.
Twenty-eight days after treatment, 22 of 158 patients (13.9%) in the remdesivir cohort died, compared to 10 of 78 untreated control patients (12.8%)—a difference the researchers concluded was not statistically significant.
Among secondary outcomes, 8 of 71 patients treated with remdesivir (11.3%) died within 10 days of illness onset, compared with 7 of 47 placebo patients (14.9%).
Side effect difference
Eighteen of 155 remdesivir patients evaluated (11.6%) were taken off the drug due to side effects, compared with 4 of 78 placebo patients (5.1%). Adverse events were reported in 102 remdesivir recipients (65.8%) vs. 50 of 78 placebo recipients (64.1%).
A draft version of the Chinese study results was accidentally published April 23 by the World Health Organization (WHO) on its website.
The trial—which was originally supposed to enroll 453 patients—was the second Phase III study of remdesivir in China to end early due to low enrollment. The inability to enroll patients was a consequence of the decrease in COVID-19 cases since the winter, the trial sponsor, China’s Capital Medical University, stated on the study’s page on ClincalTrials.gov: “The epidemic of COVID-19 has been controlled well in China, no eligible patients can be enrolled at present.”
On April 15, Capital Medical University also disclosed on ClincalTrials.gov that enrollment was suspended in a Chinese trial designed to assess remdesivir in patients with mild-to-moderate forms of COVID-19 (NCT04252664). That trial was a randomized, double-blind, placebo-controlled multicenter study intended to evaluate remdesivir’s safety and efficacy in hospitalized adults. The trial’s estimated enrollment was 308 patients.
However, remdesivir appears to have perform better in the severe COVID-19 Phase III trial, according to leaked results first reported by STAT after it obtaining a video discussion by the investigator conducting the study at University of Chicago, one of 169 treatment sites.
Remdesivir treatment in severe COVID-19 patients led to rapid recoveries in fever and respiratory symptoms with nearly all patients discharged in less than a week, according to the report. Gilead responded with a statement emphasizing: “The totality of the data need to be analyzed in order to draw any conclusions from the trial,” while UChicago Medicine stated: “Drawing any conclusions at this point is premature and scientifically unsound.”