A report has come out in the NEJM on the experience with “compassionate use” (off-label or not yet approved) of the Gilead drug remdesivir in the Covid-19 epidemic. Here are the inclusion criteria:
Patients were those with confirmed SARS-CoV-2 infection who had an oxygen saturation of 94% or less while they were breathing ambient air or who were receiving oxygen support. Patients received a 10-day course of remdesivir, consisting of 200 mg administered intravenously on day 1, followed by 100 mg daily for the remaining 9 days of treatment. This report is based on data from patients who received remdesivir during the period from January 25, 2020, through March 7, 2020, and have clinical data for at least 1 subsequent day.
Presented are data from 53 patients in the US, Canada, Europe, and Japan. They were in bad shape – 30 of them were on ventilators and 4 were receiving ECMO treatment (blood oxygenation outside the lungs). At the time of the manuscript’s preparation, 25 patients had been discharged from the hospital, and 7 had died (6 of whom had been on ventilation). Overall, clinical improvement was seen in 36 of the 53 patients.
That’s pretty much it – those are the numbers we have. The study did not even collect viral-load data, so we can’t say what that was like or if it correlated with clinical outcome. What do they tell us? Not much, because this (like so many others early in this epidemic) is not a controlled study. What if you had a list of patients of similar age and gender and pre-existing conditions in similar shape, and didn’t give them remdesivir, but just standard-of-care without it? We have just described an appropriate control group, and you can see why you’d want one in order to say anything useful. To be honest, those outcomes sound not unlike what you might expect from treatment without remdesivir, but who knows? Needless to say, you would also want to look at this in a lot more than 53 patients to be sure. It’s effect size again: no one expects remdesivir to have miraculous get-up-and-walk effects; what effects it does have are going to be more subtle. And that means you’re going to have to have a sufficiently powered (i.e. larger and well-controlled) study to see them.
The authors themselves know this well, of course, and they make no claims. Comparing the 28-day mortality in this study to others, it might be a bit better, but as the paper concludes, “Measurement of efficacy will require ongoing randomized, placebo-controlled trials of remdesivir therapy.” At the moment it is literally impossible to say. If you’d like more detailed reasons why this is so, I can recommend this analysis (hat tip to Bruce Booth on Twitter). I’m aware that that author’s last objection is that “big pharma” was involved, which (like Bruce) I’ll let slide for now, only noting that Big Pharma and Big Biotech and Big Whoever are going to be the only things that are going to provide new treatments for this disease at all, so get braced for that, is my advice.
And here is an open letter from Gilead’s CEO, Daniel O’Day. Some excerpts:
Remdesivir is an investigational treatment and has not been approved for use anywhere in the world. In the broader efforts to determine whether it is a safe and effective treatment, we have some way to go. . .In studying remdesivir, the question is not just whether it is safe and effective against COVID-19 but in which patients it shows activity, how long should they receive treatment and at what stage of their disease would treatment be most beneficial. Many answers are needed, which is why we need multiple types of studies involving many types of patients. Some of these answers will start to emerge in the coming weeks as we receive the first data from the various clinical trials underway.
It goes on to give brief details of seven of those trials, the first of which will read out preliminary data around the end of April. Note how there is nothing in there about how it would be somehow unethical not to give remdesivir to everyone, how there is nothing in there about how controlled trials are a waste of time, etc. I refer, of course, to the statements of Dr. Didier Raoult on his hydroxychloroquine/azithromycin combination. Put those claims next to O’Day’s for a quick lesson in what someone trustworthy says about an investigational drug.
Note: The next post this morning will take us back into the hydroxychloroquine world. . .