Minneapolis/Berlin: With dueling data released on Gilead Sciences Inc.’s potential coronavirus drug, the jury remains out on how well the medicine works.
There are two big reasons why. While Anthony Fauci, the National Institute for Allergy and Infectious Diseases director, said a U.S. government-run trial met its overall target, full details haven’t been published. At the same time, the only large, rigorous study for which full data is public — a Chinese trial published in The Lancet medical journal on Wednesday — showed the opposite.
The competing trials are the latest example of how science has taken a back seat to optimism in the rush to find a way out of the coronavirus crisis that has paralyzed economies around the world. Dozens of companies are studying 11 potential therapies and 137 vaccines in an effort to get the virus under control. Gilead’s experimental drug remdesivir, which had already been tested on other coronaviruses, is one of the most closely watched.
“It’s not just a single trial that’s going to hold the truth here,” said John Norrie, a professor of medical statistics and trial methodology at the University of Edinburgh. The real implication of the U.S. government study won’t be clear until it’s been scrutinized by outside scientists and published in a top medical journal, he said.
“The bottom line is, you can’t rely on press releases,” Norrie said.
Nevertheless, early glimmers from encouraging data are likely to increase pressure on U.S. regulators to clear a path for remdesivir to reach the market.
President Donald Trump, who has aggressively pushed for experimental therapies to treat Covid-19, praised the findings as a substantial step forward and nodded toward an eventual approval of the medicine by the U.S. Food and Drug Administration. A decision on the medicine could come as soon as this week, with agency officials saying they have been working closely with Gilead.
“I want them to go as quickly as they can,” Trump said. “We want everything to be safe. But we would like to see very quick approvals, especially with things that work.”
The FDA “has been engaged in sustained and ongoing discussions with Gilead Sciences regarding making remdesivir available to patients as quickly as possible, as appropriate,” said spokesman Michael Felberbaum in an email.
In an interview Wednesday, Gilead Chief Executive Officer Daniel O’Day said the company had enough of the drug packed and ready to ship to treat 50,000 patients as soon as U.S. regulators clear it for use. He confirmed the company is in talks with the FDA about an emergency use authorization for the therapy.
Scientists will be looking for answers to the same major questions that are asked of any clinical trial. They’ll want to know whether remdesivir worked, whether it is safe and if there’s a good biological explanation for how patients fared. Most of those questions remain open.
They will also need to know the results of the entire trial. The preliminary findings were released after a safety monitoring committee conducted an interim analysis that showed patients on remdesivir recovered more quickly. Only about half the 1,063 patients in the trial were included in the review, according to Aneesh Mehta, an infectious-disease doctor at the Emory University School of Medicine and an investigator on the trial. The final results may yield a somewhat different conclusion.
While Fauci called the results “quite good news,” other scientists and regulators will weigh the magnitude of the benefit. The experimental drug helped patients who recovered get better four days faster than those who took a placebo, meeting the primary goal of the study. But the results show only a trend toward improving survival, Fauci said. In clinical trial terms, that means it wasn’t clear whether the difference was due to chance.
The venue for Fauci’s comments was unorthodox. A small pool of reporters came to the Oval Office expecting news out of a meeting between Trump and Louisiana Governor John Bel Edwards. Instead, they got a briefing from Fauci on the remdesivir findings.
That briefing followed by just hours the release of Gilead’s own statement about the government results. Companies often release so-called “top-line” findings as soon as they know whether a trial succeeded or failed overall. But it’s unprecedented for a company to announce the success or failure of a study it didn’t run. Gilead declined to comment on the timing.
Gilead said its in-house study showed that patients who got remdesivir for five days did just as well as those on the 10-day course of treatment used by the government study and other trials. This would be important information if remdesivir is proven to work against the virus, because it would essentially double the number of people who could be treated. But the Gilead results don’t show whether the drug helped patients more than the current standard treatment.
The shortened duration could significantly increase treatment courses Gilead can provide with its current supply amounting to 1.5 million individual doses, O’Day wrote in an open letter on the company’s website.
“We now know two things: that remdesivir appears to shorten time to recovery and when treating patients with severe disease, a five-day treatment course is potentially as effective as 10 days,” O’Day wrote.
The company also plans to study remdesivir on a broader group of patients and explore how it might work with other therapies. It is also working to build a consortium with other drug and chemical manufacturers to ramp up supply, and is seeking ways to make it available to developing countries.
There’s a history of confusing and premature data on remdesivir. Last week, the negative results from a trial in China were accidentally posted on a World Health Organization web page.
The Lancet published the full Chinese trial involving 237 patients on Wednesday. Though researchers had to stop the trial early after not being able to recruit the 453 they had originally planned, they found that remdesivir didn’t help patients get better faster, and it didn’t have an effect on deaths. Most curious is that it didn’t show an effect on the amount of virus in patients’ bodies — an unexpected finding since the drug is an antiviral.
Fauci dismissed the results of the Chinese study, saying it didn’t have enough patients or the right design to be definitive. The U.S. study, in which more than 1,000 participants were randomly assigned to either get the drug or a placebo, is more conclusive with a clear endpoint, he said.
“I don’t like to pooh-pooh other studies,” Fauci said, “but that’s not an adequate study and everybody in the field feels that.”
And though there was no difference in adverse events between the trial groups in the Chinese study, more patients in the remdesivir group dropped out because of side effects including heart failure. The NIH didn’t release side effect data from its trial.