Enlarge /. A vial with remdesivir during a press conference about the start of a study with severely COVID-19 patients in Hamburg on April 8, 2020.
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The U.S. Food and Drug Administration on Thursday granted full approval of the antiviral drug Remdesivir for the treatment of COVID-19 – just days after a massive global study concluded the drug was of no benefit.
"The FDA is committed to accelerating the development and availability of COVID-19 treatments during this unprecedented public health emergency," FDA Commissioner Stephen Hahn said in a statement. "Today's approval is supported by data from multiple clinical studies that have been rigorously reviewed by the agency and represent a major scientific milestone in the COVID-19 pandemic."
The FDA made its decision based on three clinical trials of Remdesivir, a repurposed experimental antiviral drug with the brand name Veklury. One of them was a randomized, double-blind, placebo-controlled study by the National Institute for Allergies and Infectious Diseases. It included 1,062 hospitalized COVID-19 patients, 541 of whom were receiving remdesivir. The study concluded that remdesivir reduced the median recovery time from infection from 15 days to 10 days. The researchers who conducted the study defined a patient's "recovery" as either a patient who was discharged from hospital – regardless of whether the patient had persistent symptoms that restricted activity or required supplemental oxygen at home – or as a patient who stayed in the hospital but they no longer need medical care, for example if they are kept in hospital for infection control purposes.
The other two studies considered by the FDA were conducted by Gilead, the company that makes remdesivir. One study looked at around 600 people with moderate COVID-19 cases. The patients were divided into three groups of about 200 people each – a group with a 10-day remdesivir course, a group with a 5-day course, and a control group with standard treatments. On day 11 of treatment, the group with the 5-day remdesivir course showed a statistically significant improvement in symptom scores compared to the control group. However, the group that received a 10-day remdesivir course showed no statistically significant improvement over the control group.
The other Gilead study looked at 400 patients with severe COVID-19. They were roughly evenly split into just two groups – one group that received a 5-day remdesivir course and one group that received a 10-day course. There were no statistically significant differences in recovery or death between the two groups.
"Veklury's (FDA) approval marks an important milestone in efforts to fight the pandemic by providing effective treatment that helps patients recover faster and which in turn helps conserve scarce healthcare resources" said Barry Zingman in a Gilead press release. Zingman is a professor at Albert Einstein College of Medicine and one of the researchers who conducted the NIAID study on remdesivir.
However, the FDA's approval of remdesivir follows data from the drug's fourth and largest study, and that study showed no benefit. The data comes from the World Health Organization's massive solidarity study, which set up an international network of studies that enrolled nearly 12,000 patients in 500 locations in over 30 countries and tested several reused therapeutics. Remdesivir was originally developed over a decade ago as a potential treatment for hepatitis C and RSV (respiratory syncytial virus). It was also tested against Ebola, but was defeated by other treatments.
According to preliminary results from the Solidarity Study, published online last week before its scheduled publication in the New England Journal of Medicine, remdesivir was given to 2,743 patients and its results were compared with those of 2,708 patients given standard treatments. Between the two groups, the WHO found that remdesivir did not reduce mortality. It didn't change how many patients needed mechanical ventilation, nor did it change the proportion of patients discharged after seven days of hospitalization.
When the solidarity study data was first released, Gilead blew the results, saying, "The emerging data does not seem to agree with more robust evidence from several randomized, controlled trials confirming the clinical utility of (Remdesivir)."
Can't fumble that
However, in a press conference on Friday, the WHO struck back, arguing that the data were indeed more robust than the smaller studies previously conducted and that they should definitely be included in any regulatory or clinical decision.
"It's the largest study in the world," noted Soumya Swaminathan, WHO chief scientist. And unlike the NIAID study, which used a somewhat subjective clinical scoring system to compare disease progression and a number of definitions of "recovery", the solidarity study only compared clear, indisputable results: mechanical ventilation, hospital discharge, and Death .
"(Death is) not a soft end point," said Swaminathan. "You cannot falsify this endpoint."
Swaminathan also noted that it was clear that the FDA did not have the solidarity study data when it made its decision to approve remdesivir. However, she stressed that the WHO had provided Gilead with these data in advance. "You first saw the results on September 23," she said long before they were made public. But "it seems the results were not taken into account – not made available to the FDA," she said.
Although the comments suggest that WHO does not support the FDA's decision to approve remdesivir for the treatment of COVID-19, WHO experts also suggested that FDA approval may be irrelevant. Instead, expert clinical guidelines for patient care are most important.
"Regulators can put items on an approved list," WHO Executive Director Michael Ryan said at the press conference. "That doesn't necessarily mean they will be used in a particular practice unless they go into the clinical guidance given to doctors and nurses."
The WHO noted that it is working on such clinical guidelines and treatment recommendations and expects them to be published in three to four weeks.