- Coronavirus drug remdesivir was called the standard of care for COVID-19 patients in late April when Dr. Anthony Fauci announced the early results of an extensive study.
- Fauci said the drug can speed up recovery, although the COVID-19 treatment did not affect mortality. The drug should be combined with other therapies in a future study.
- The preliminary study has now finally been published, revealing that remdesivir isn’t the coronavirus miracle cure that some may have hoped it’d be.
The world has been battling the novel coronavirus for more than five months now, with more than 5.5 million people having been infected during this time. As of Monday morning, nearly 348,000 people died of COVID-19 complications, and millions of people are out of work as a result of the severe social distancing measures put in place around the world since March. All those sacrifices were not in vain, as we’ve seen tremendous progress from the medical community during that time. More than 2.27 million people have already recovered from COVID-19, and doctors have a much better understanding of how the SARS-CoV-2 spreads, how it infects the body, and how it kills. They also know it can be neutralized, and plenty of new therapies are being developed, including drugs repurposed for the new infection as well as new treatments developed just to combat coronavirus.
There’s no magical cure, however, and only one of these promising drugs has been upgraded to “standard” use in COVID-19. Remdesivir is the medicine in question, a drug that Dr. Anthony Fauci lauded in late April when he explained the results of a massive remdesivir study whose conclusions were very promising. That study was finally published online on Friday, and the results are indeed encouraging. However, just as Fauci cautioned back in April, it’s not all good news.
“This is really quite important,” Fauci told reporters last month, comparing the remdesivir study to 1986 “when we were struggling for drugs for HIV, and we had nothing.” He added, “This will be the standard of care,” noting that more research will be required and that the next step will be combining remdesivir to another drug.
The study was published in preliminary form in The New England Journal of Medicine on Friday, and it’ll require updating once the rest of the data from the 1,063 patients is gathered. But the conclusions section delivers the good news. “Remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with Covid-19 and evidence of lower respiratory tract infection,” the authors of the paper explained.
But that’s not all the study says. Later in the discussion section, it’s made clear that remdesivir alone isn’t enough. “These preliminary findings support the use of remdesivir for patients who are hospitalized with Covid-19 and require supplemental oxygen therapy,” the researchers write. “However, given high mortality despite the use of remdesivir, it is clear that treatment with an antiviral drug alone is not likely to be sufficient. Future strategies should evaluate antiviral agents in combination with other therapeutic approaches or combinations of antiviral agents to continue to improve patient outcomes in Covid-19.”
As a reminder, researchers included in the study patients from the US and several other countries and divided them into two groups. 538 patients were assigned remdesivir and 521 were given a placebo, with doctors not knowing which medicine their patients received. The researchers found that those who received remdesivir recovered in an average of 11 days, 4 days sooner than the control group. Remdesivir did not have a statistically relevant effect on mortality, though. After 14 days, 7.1% of patients on remdesivir died, compared to 11.9% on placebo.
One of the problems with the study is that the researchers moved the goalposts in the middle of it. They divided the patients into eight categories, as seen below, and assessed their recovery by the 28th day after enrollment. Initially, the study was supposed to look at the outcome of patients after 15 days, but the scientists decided to extend the period once they learned that COVID-19 recovery can take a much longer time than anticipated:
The primary outcome measure was the time to recovery, defined as the first day, during the 28 days after enrollment, on which a patient satisfied categories 1, 2, or 3 on the eight-category ordinal scale. The categories are as follows: 1, not hospitalized, no limitations of activities; 2, not hospitalized, limitation of activities, home oxygen requirement, or both; 3, hospitalized, not requiring supplemental oxygen and no longer requiring ongoing medical care (used if hospitalization was extended for infection-control reasons); 4, hospitalized, not requiring supplemental oxygen but requiring ongoing medical care (COVID-19–related or other medical conditions); 5, hospitalized, requiring any supplemental oxygen; 6, hospitalized, requiring noninvasive ventilation or use of high-flow oxygen devices; 7, hospitalized, receiving invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); and 8, death.
One other issue with the study is that it was stopped after a panel of experts charged with safeguarding the patients notified the National Institute of Allergy and Infectious Diseases (NIAID) there was a statistically significant benefit of remdesivir. As a result, the study failed to explain whether remdesivir can reduce mortality.
“It’s clear from the publication that the study was stopped prior to the completion of a significant number of patients,” Cleveland Clinic cardiologist Steven Nissen told Stat. “By stopping it early, the scientific community was deprived of the opportunity to determine whether remdesivir can or cannot reduce mortality.”
Finally, as of April 28th, only 391 patients in the remdesivir group and 340 in the placebo group had finished 29 days of the study, which means data wasn’t available for the remainder of patients, including 132 and 169 patients in the two cohorts. That’s why the findings of the study are preliminary, and some of the figures it presents might change once the full data is accounted for.
One other issue with the study might be the quality of the two groups. Slightly more placebo subjects started out in the more severe groups.
“I am not concluding from this that the treatment is not reducing time to recovery; it makes me less convinced that there is a mortality benefit when more placebo than intervention ended up in the highest risk group,” Center for Health Policy and Outcomes at Memorial Sloan Kettering Cancer Center director Peter Bach told Stat. He said a different remdesivir trial from Wuhan, China concluded that time to benefit was not significant, and it showed no mortality benefit. The doctor also criticized a separate study from remdesivir maker Gilead that compared two different durations of treatment without having a control group.
With all that in mind, the study still proves that the drug can help specific categories of COVID-19 patients recover faster. And it looks like the earlier patients are treated with remdesivir, the better they may fare.
Put differently, access to extensive testing might reduce complications and speed up access to proper treatment, remdesivir included. Gilead told Stat that it’ll produce results by the end of the month from a study that compared remdesivir to the standard of care in patients with moderate cases of COVID-19.
