Remdesivir, the drug developed as a treatment for Covid-19 by Gilead Sciences, helped patients with “moderate” disease recover more quickly when they received it for five days, but the benefit was not statistically significant when given for 10 days, the company said Monday.
The new data, from a study conducted by the company, add to the evidence that the medicine is at least somewhat effective treatment for Covid-19. But they will also likely add to the debate of exactly how effective the remdesivir is, and in what patients.
“For most clinicians when we see this, it’s heartening,” said Nahid Bhadelia, medical director of the special pathogens unit at Boston Medical Center. “But at the same time it’s frustrating to get the data through a press release rather than to see the data.” She said that until the data are published, many physicians will be in a “gray area” where they are not quite sure how to use the drug. She said the results only emphasize the need to identify patients who are deteriorating so they can get the drug sooner. “To me, it means we need to create a public health infrastructure that leads to early diagnosis.”
An earlier study showed that patients with severe disease who received remdesivir recovered four days faster than similar patients who received placebo.
The patients in this study had what was termed “moderate” disease, meaning that they were hospitalized but did not need mechanical ventilation at any time. Unlike the study in more severe patients, this study did not give a placebo to those who did not receive the drug, meaning that both physicians and patients knew who was getting remdesivir and who wasn’t.
Patients who received remdesivir for five days were 65% more likely to show improvement on a seven-point scale, where 1 was death and 7 was “not hospitalized,” at the end of 11 days. Those who received remdesivir for 10 days were 31% more likely to have improved on the seven-point scale, but that difference was not statistically significant, meaning that it might have occurred by chance.
Those results broadly line up with the results of the severe study, run by the National Institutes of Health, in which patients were 50% more likely to have experienced an improvement on a similar symptom scale after 15 days. In a Chinese study of remdesivir that did include a placebo group, patients who received the drug improved 23% faster but the result was not statistically significant.
Why would remdesivir work better when given for five days than when given for 10? It will be difficult to even wager guesses until the data are published in full. Right now, Gilead has made only limited information available, and the results have not been peer-reviewed by other scientists.
One possibility is that the difference is due only to chance. The researchers running the NIH study changed the main goal of their study before it read out because they worried that looking at the data on just a single day would make it more likely that the study would fail when the drug actually worked. It could be that looking at the benefit only at the 11-day time point led to a chance result. The Gilead study changed its main goal, too: Researchers originally planned to look at the results at 14 days, not 11.
A Gilead spokesperson said the nature of the seven-point scale may have affected the outcome, because discharge from the hospital counted as an improvement. Remdesivir is given as an IV in the hospital, so it may be that fewer patients in the 10-day group left the hospital by day 11 compared to those in the five-day group because they had not stopped the drug yet. The spokesperson noted that the study was not designed to compare the five-day and 10-day treatments.
But it is also possible that a shorter course of therapy is more effective. On April 29, Gilead released results, also by press release, of the study that compared the five- and 10-day courses of remdesivir in severe Covid-19 patients without a control group. In that study, patients who received five-day courses also seemed to recover more often, although, again, the difference was not statistically significant.
Brian Abrahams, an analyst at RBC Capital Markets, wrote in a note to investors that there seems to be “growing evidence” that the five-day treatment course is as good or better. He called this “somewhat curious” given that there are no obvious side effects that would make getting the drug for longer worse. In the results released Monday, there were 97 adverse events in the five-day group, 106 in the 10-day group, and 90 among those who received standard treatment.
For now, the only information about whether remdesivir improved patients’ odds of surviving is for 11 days of treatment. There were no deaths in the five-day group, two in the 10-day group, and four among the patients who received only standard treatment.
Peter Bach, director of Memorial Sloan Kettering’s Center for Health Policy and Outcomes, said that it’s very possible that the 10-day group did worse because doctors waited for patients to complete treatment before discharging them. Including a placebo group could have prevented this, he said. He also noted that, should Gilead begin charging a price for remdesivir instead of giving it away for free, the lower death rate in this population would support a much lower price than previous studies. “If you have to treat more people to prevent a death, the price per treated patient needs to decrease,” Bach said.
Abrahams, the RBC analyst, wrote that the data “does not change” his team’s view that remdesivir is an important tool for doctors during the pandemic. Umer Raffat, an analyst at Evercore ISI, an investment bank, summed up the reaction many will probably have to the results. “We need more data.”