What do you think? Leave a respectful comment.

Critical study of Gilead drug shows coronavirus patients responding to treatment, NIH says

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.

The preliminary data showed that the time to recovery was 11 days on remdesivir compared to 15 days for placebo, a 31% decrease. The mortality rate for the remdesivir group was 8%, compared to 11.6% for the placebo group; that mortality difference was not statistically significant.

That is “the first convincing evidence that an antiviral drug can really benefit COVID-19 patients, specifically hospitalized COVID-19 patients,” said Frederick Hayden, a professor emeritus of clinical virology and medicine at the University of Virginia School of Medicine. “This will change the standard of care in the United States and other countries for the patients who have been shown to be benefited,” he said, adding that determining the exact group that should receive the drug will require further examination of the data.

READ MORE: Projecting COVID-19 death tolls is as difficult as ever. Comparing them to other causes of death is easier — and staggering

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.

Aneesh Mehta, a physician at Emory University and an investigator in the NIAID study, said the results were “robust enough” to report preliminary findings, but a full analysis of all the data will be required to fully understand the drug’s effect. The time to recovery seen in the final analysis “could be shorter, it could be longer. We don’t know yet.” Mehta also expects the final results to do some analyses on which patients might benefit most from remdesivir.

The FDA previously issued an emergency authorization for the malaria drug hydroxychloroquine to treat COVID-19, even though at least some studies suggested 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 courses. 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 untreated. 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.

READ MORE: Gilead CEO: We’re going to make sure that access is not an issue with remdesivir

Patients in the trial generally lived, though this may be because their illness was not that severe to begin with. For most of the study, patients already on ventilators were not enrolled.

Eight percent of the patients treated with five days of remdesivir died, compared to 11% of the patients treated for 10 days. Outside of Italy, where 77 patients were treated, the overall mortality rate across the entire study was 7%, Gilead said. Those mortality rates are lower than those seen in other studies, which have been in the teens and twenties.

Only 5% of patients in the five-day group and 10% in the 10-day group had side effects that led to a discontinuation. The most common bad effects — and it’s impossible to tell which were from the drug — were nausea and acute respiratory failure. High liver enzymes occurred in 7.3% of patients, with 3% of patients discontinuing the drug due to elevated liver tests.

A full evaluation of the results will have to wait until complete data are available.

In the China study, also published Wednesday in the Lancet, investigators found that remdesivir “did not significantly improve the time to clinical improvement, mortality, or time to clearance of virus in patients with serious COVID-19 compared with placebo.”

There was a 23% improvement in time to clinical improvement for remdesivir compared to placebo, but the difference was not statistically significant. At the median, remdesivir-treated patients improved in 20 days compared to 23 days for placebo patients. At one month, 14% of the remdesivir patients had died compared to 13% of the placebo-treated patients.

The China study enrolled patients with more severe COVID-19 than the study conducted by NIAID. The China study was also stopped early because of difficulties enrolling patients as the pandemic waned in China.

Hayden, the University of Virginia virologist, was one of the investigators in the China study and pointed to the similarity of the results. He said that while the NIAID investigators had been able to enroll enough patients, the decrease in cases in Wuhan due to the lockdown had made that impossible. “I was struck by the consistency,” he said.

This article is reproduced with permission from STAT. It was first published on April 29, 2020. Find the original story here.

The Latest