| |
Critical study of Gilead's Covid-19 drug shows patients are responding to treatment, NIH says
|
| |
| |
- FDA May Announce emergency use authorization
https://www.nytimes.com/2020/04/29/us/coronavirus-usa-cases-deaths.html?action=click&module=Spotlight&pgtype=Homepage#link-2d010b61
Meeting with reporters at the White House, Dr. Fauci cautioned that the results of the study overseen by his agency, the National Institute of Allergy and Infectious Disease, still need to be properly peer reviewed but expressed optimism that it could make a difference in speeding up the recovery of some patients infected with the virus.
Dr. Fauci said the federal trial indicated that the drug remdesivir could shorten the time to recovery by about a third. "Although a 31 percent 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," Dr. Fauci said. "This is very optimistic."
Remdesivir is not yet licensed or approved in the United States or anywhere in the world "and has not yet been demonstrated to be safe or effective for the treatment of Covid-19," according to Gilead.....Gilead will share additional remdesivir data from the company's open-label Phase 3 SIMPLE trial in patients with severe COVID-19 disease shortly. This study will provide information on whether a shorter, 5-day duration of therapy may have similar efficacy and safety as the 10-day treatment course evaluated in the NIAID trial and other ongoing trials. Gilead expects data at the end of May from the second SIMPLE study evaluating the 5- and 10-day dosing durations of remdesivir in patients with moderate COVID-19 disease......A representative for Gilead said in an email Wednesday that "as we have done since the beginning of the pandemic, we have been sharing information, transparently and as it becomes available, with the administration, other officials and the public."....The spokesman, Ryan McKeel, said the company could not speculate on what actions the federal government would take. "However, we are continuing to discuss with them the growing body of evidence for remdesivir as a potential treatment for COVID-19, with the goal of making remdesivir more broadly available for patients in urgent need of treatment."
About the SIMPLE Trials
Gilead initiated two randomized, open-label, multi-center Phase 3 clinical trials for remdesivir, the SIMPLE studies, in countries with high prevalence of COVID-19 infection.
The first SIMPLE trial is evaluating the safety and efficacy of 5-day and 10-day dosing regimens of remdesivir in hospitalized patients with severe manifestations of COVID-19. The initial phase of the study randomized 397 patients in a 1:1 ratio to receive remdesivir 200 mg on the first day, followed by remdesivir 100 mg each day until day 5 or 10, administered intravenously, in addition to standard of care. An expansion phase of the study was recently added and will enroll an additional 5,600 patients, including patients on mechanical ventilation. The study is being conducted at 180 trial sites around the world, including sites in the United States, China, France, Germany, Hong Kong, Italy, Japan, Korea, the Netherlands, Singapore, Spain, Sweden, Switzerland, Taiwan and the United Kingdom.
A second SIMPLE trial is evaluating the safety and efficacy of 5-day and 10-day dosing durations of remdesivir administered intravenously in patients with moderate manifestations of COVID-19, compared with standard of care. The results from the first 600 patients of this study are expected at the end of May.
------------
Critical study of Gilead's Covid-19 drug shows patients are responding to treatment, NIH says
By Matthew Herper @matthewherper and Adam Feuerstein @adamfeuerstein
April 29, 2020
A government-run study of Gilead's remdesivir, perhaps the most closely watched experimental drug to treat the novel coronavirus, showed that the medicine is effective against Covid-19, the disease caused by the virus.
In a statement on Wednesday, the National Institute of Allergy and Infectious Diseases, which is conducting the study, said preliminary data show patients who received remdesivir recovered faster than similar patients who received placebo.
The finding - although difficult to fully characterize without full, detailed data for the study - would represent the first treatment shown to improve outcomes in patients infected with the virus that put the global economy in a standstill and killed at least 218,000 people worldwide.
During an appearance alongside President Trump in the Oval Office, Anthony Fauci, the director of NIAID, part of the National Institutes of Health, said the data are a "very important proof of concept" and that there was reason for optimism. He cautioned the data were not a "knockout." At the same time, the study achieved its primary goal, which was to improve the time to recovery, which was reduced by four days for patients on remdesivir.
Over the past few weeks, there have been conflicting reports about the potential benefit of remdesivir, a drug that was previously tried in Ebola. As previously reported by STAT, an early peek at Gilead's study in severe Covid-19 patients, based on data from a trial at a Chicago hospital, suggested patients were doing better than expected on remdesivir. Days later, a summary of results from a study in China showed that patients on the drug did not improve more than those in a control group.
Full results from the China study were also released Wednesday.
But the NIAID study, which was not expected to be released so soon, was by far the most important and rigorously designed test of remdesivir in Covid-19. The study compared remdesivir to placebo in 800 patients, with neither patients nor physicians knowing who got the drug instead of a placebo, meaning that unconscious biases will not affect the conclusions.
The main goal of the study is the time until patients improve, with different measures of improvement depending on how sick they were to begin with. While the result means that the drug helps patients improve faster, it is not possible to say how dramatic those improvements are.
Scott Gottlieb, the former commissioner of the Food and Drug Administration, said he expected there was enough evidence for the agency to issue an "emergency use authorization" for remdesivir.
"Remdesivir isn't a home run but looks active and can be part of a toolbox of drugs and diagnostics that substantially lower our risk heading into the fall," he said.
The FDA previously issued an emergency authorization for the malaria drug hydroxychloroquine to treat Covid-19, even though at least some studies suggesting the medicine was not effective. "If hydroxychloroquine met [the emergency] standard, then remdesivir would have seemed to cross that line a while ago, especially in the setting of treating critically ill patients," Gottlieb said.
Remdesivir, which must be given intravenously, is likely to remain a treatment for patients who are hospitalized. But it is also likely that it will be most effective in patients who have been infected more recently, said Nahid Bhadelia, medical director of the special pathogens unit at Boston Medical Center.
"We know that with most antiviral medications the earlier you give it the better it is." said Bhadelia, who had experience giving remdesivir as an experimental treatment for Ebola in Africa, where results are less encouraging. That means that better diagnostic testing will be essential to identifying patients who could benefit. "What will be important is that we find people on the outpatient side," Bhadelia said. "Again, testing becomes important, we want to have them come to the hospital as soon as possible."
Although the data have not yet been released, it's standard procedure for pharmaceutical and biotechnology companies to release market-moving information as soon as they have it, due to regulatory requirements.
Gilead on Wednesday did release data from its own study of remdesivir in patients with severe Covid-19. This study showed similar rates of clinical improvement in patients treated with a five-day and 10-day course of remdesivir, the company said.
"Unlike traditional drug development, we are attempting to evaluate an investigational agent alongside an evolving global pandemic. Multiple concurrent studies are helping inform whether remdesivir is a safe and effective treatment for COVID-19 and how to best utilize the drug," said Merdad Parsey, Gilead's chief medical officer, in a statement.
Gilead said that its own study in severe patients showed that it may be possible to treat patients with a five-day treatment of remdesivir, not the 10-day course that was used in the NIAID trial.
The company's study is enrolling approximately 6,000 participants from 152 different clinical trial sites all over the world. The data disclosed Wednesday are from 397 patients, with a statistical comparison of patient improvement between the two remdesivir treatment arms - the five-day and 10-day treatment course. Improvement was measured using a seven-point numerical scale that encompasses death (at worst) and discharge from hospital (best outcome), with various degrees of supplemental oxygen and intubation in between.
The study design means that by itself it doesn't reveal much about how well remdesivir is working, because there is no group of patients who were not treated with the drug. The conclusion is that the two durations of treatment are basically the same.
Peter Bach, the director of the Center for Health Policy and Outcomes at Memorial Sloan Kettering Medical Center, said he is eager to see the data from the NIAID study but renewed his criticism of Gilead's severe study for lacking a control group of untreated patients. That would have allowed researchers to make important conclusions about how the drug works that are just not possible now, he said.
"They've squandered an unbelievable opportunity," Bach said. "It's not going to tell us what to do with 80-year-olds with multiple comorbidities compared to 30-year-olds who are otherwise healthy. We're still going to be foundering around in the dark, or at least in a dim room, when we could have learned more."
In the study, the median time to clinical improvement was 10 days in the five-day treatment group and 11 days in the 10-day treatment group. More than half of the patients in both groups were discharged from the hospital by day 14. At day 14, 64.5% of the patients in the five-day group and 53.8% of the patients in the 10-day group achieved clinical recovery.
|
|
| |
| |
|
|
|
