Trials on remdesivir as potential Covid-19 treatment show conflicting results, but experts are hopeful
Two separate clinical trials involving the drug remdesivir as a potential treatment for coronavirus have generated two different results. The first one, conducted by the National Institute of Allergy and Infectious Diseases (NIAID), US says that the drug accelerated the recovery time of Covid-19 patients by 31%, from 15 days in patients who got a placebo to 11 days in people treated with remdesivir.
The second one appears to counter the results of the NIAID study as the median time to recovery for patients taking remdesivir was 21 days, compared with 23 days for those getting a placebo.
There is currently no approved treatment or vaccine for Covid-19, which has killed over 227,670 globally as of April 30 in the pandemic. Worldwide, more than 3,194,660 cases have been reported, according to the Johns Hopkins tracker.
Results of the US study
Hospitalized patients with advanced Covid-19 and lung involvement who received remdesivir recovered faster than similar patients who received a placebo, according to a preliminary data analysis from a randomized, controlled trial involving 1,063 patients, which began on February 21.
The results indicate that patients who received remdesivir had a 31% faster recovery time than those who received a placebo. The impact on deaths is, however, not as clear cut. The mortality rate was 8% in people given remdesivir and 11.6% in those given a placebo. “Specifically, the median time to recovery was 11 days for patients treated with remdesivir compared with 15 days for those who received a placebo. Results also suggested a survival benefit, with a mortality rate of 8.0% for the group receiving remdesivir versus 11.6% for the placebo group,” says the initial results of the trial known as the ‘Adaptive Covid-19 Treatment Trial, or ACTT.’
The first trial participant in the ACTT trial was an American who was repatriated after being quarantined on the Diamond Princess cruise ship that docked in Yokohama, Japan. The person volunteered to participate in the study at the first study site, the University of Nebraska Medical Center/Nebraska Medicine, in February 2020. A total of 68 sites ultimately joined the study -- 47 in the US and 21 in countries in Europe and Asia.
More detailed information about the trial results, including more comprehensive data, will be available in a forthcoming report, according to NIAID.
Dr Anthony Fauci, NIAID Director, said, “The data shows that remdesivir has a clear-cut, significant, positive effect in diminishing the time to recovery.” He added, “Although a 31% improvement doesn't seem like a knockout 100 percent, it is a very important proof of concept because what it has proven is that a drug can block this virus.”
Professor Philip Bath, chair and head of the Division of Clinical Neuroscience, University of Nottingham, said in a statement, that more information is needed from NIH and it is “certainly not a time to start using this drug until we know more.”
Gilead Sciences, which has developed remdesivir, also issued a statement, saying that the company is “aware of positive data emerging from the NIAID study of the investigational antiviral remdesivir for the treatment of Covid-19.” It said that remdesivir is not yet licensed or approved anywhere globally and has not yet been demonstrated to be safe or effective for the treatment of Covid-19.
In another statement, Gilead released some results of its clinical trial that showed a five-day course of treatment of remdesivir produced similar results to 10 days of treatment. “The study demonstrated that patients receiving a 10-day treatment course of remdesivir achieved similar improvement in clinical status compared with those taking a 5-day treatment course. No new safety signals were identified with remdesivir across either treatment group,” it said.
The analysis shows that the time to clinical improvement for 50% of patients was 10 days in the 5-day treatment group and 11 days in the 10-day treatment group. More than half of patients in both treatment groups were discharged from the hospital by day 14. “At day 14, 64.5%of patients in the 5-day treatment group and 53.8% of patients in the 10-day treatment group achieved clinical recovery,” said the release.
Results of the China study
The US data on remdesivir has come out at the same time as a trial of the same drug was conducted in China. The smaller, incomplete study published in the Lancet, found no statistically significant improvement in recovery time in severely ill Covid-19 patients given remdesivir, compared with those who got a placebo.
The study was conducted at 10 hospitals in Wuhan, China, where the pandemic first started. However, that trial was incomplete because doctors had intended to enroll 453 patients, but could not ultimately owing to the lockdown.
Between February 6 and March 12, 237 patients were enrolled and randomly assigned to a treatment group (158 to remdesivir and 79 to placebo); one patient in the placebo group later withdrew. The analysis shows that clinical improvement rates at days 14 and day 28 were not significantly different between the groups, but numerically higher in the remdesivir group than the placebo group.
The median time to clinical improvement in patients taking remdesivir was 21 days, compared with 23 days for patients taking placebo. Deaths were roughly the same in the two groups, with 14% (22/158) patients dying in the remdesivir group as compared with 13% (10/78) in the placebo group.
“Remdesivir use was not associated with a difference in time to clinical improvement. Although not statistically significant, patients receiving remdesivir had a numerically faster time to clinical improvement than those receiving placebo among patients with symptom duration of 10 days or less. Adverse events were reported in 102 (66%) of 155 remdesivir recipients versus 50 (64%) of 78 placebo recipients. Remdesivir was stopped early because of adverse events in 18 (12%) patients versus four (5%) patients who stopped placebo early,” says the researchers in their findings.
In a commentary, John David Norrie from the University of Edinburgh, UK, says that an “absence of statistical significance in an underpowered trial” implies that the findings are inconclusive. “The particular challenges of delivering pandemic trials underline the importance of data sharing, allowing rapid curation of relevant datasets for individual patient data meta-analyses. 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,” says Norrie.
The conflicting results generated many reactions from scientists, and some are hopeful. “So in one well-conducted study (237 patients) of severe #COVID19, remdesivir was not effective, but it is reported to have some efficacy in a much larger study that has not yet been published. My hunch: remdesivir will likely have a role in treatment, but want to see the data,” tweeted Isaac Bogoch, infectious diseases physician and scientist at the University of Toronto.
Eric Topol, director of the Scripps Research Translational Institute, California, said that it has been a “very confusing story.” But he added, “The good news: it looks like we now have a drug with some efficacy. And that's very good.”