We have top line results from the Adaptive COVID-19 Treatment Trial (otherwise known as ACTT). The ACTT trial is an NIH conducted, randomized, placebo controlled clinical trial on the effect of remdesivir on COVID-19 that has led to the drug receiving approval of sorts in the form of an FDA emergency use authorization.
This is big news, and I’m cautiously optimistic. I’m also holding out some skepticism for 3 major reasons:
We haven’t seen the final paper yet
I’m worried this treatment is going to be really, really expensive
I don’t own any Gilead stock
What is remdesivir?
Remdesivir is a drug that blocks viral replication.
By blocking viral replication, the hope is that you can limit both the direct damage from the virus and also contain the immune response that can cause a cytokine storm because there’s less virus to fight and thus, less immune activation.
Remdesivir was originally developed as a treatment for filoviruses (meaning filament-like viruses) that cause hemorrhagic fever syndromes, such as Ebola and Marburg.
Unfortunately, when studied in Ebola during the 2014 outbreak, it was found to be ineffective in treating these patients.
Remdesivir was subsequently found to have in vitro (read: in test tube) activity against a number of different virus families as well as activity against MERS in monkeys infected with the disease.
These findings led to optimism that remdesivir would work in COVID patients, and some (very) preliminary findings were encouraging enough to let us study the drug more (I wrote about my take on the preliminary data in a previous newsletter).
Okay, that’s enough background info. Tell me about this new trial that you seem to be so excited about
The ACTT trial compared the effect of remdesivir added to COVID treatment versus placebo added to COVID treatment.
The remdesivir group had a median time to recovery of 11 days compared to the placebo group which had a median time to recovery of 15 days. This is the 30% improvement that’s being referenced in media reports.
The remdesivir group had a death rate of 8.0% compared to the placebo group which had a death rate of 11.6%.
The improvement in time to recovery was deemed statistically significant, which means there is a less than 5% chance that the findings were due to chance (in science terms, the p value was less than 0.05).
The reduction in death is not statistically significant, but the p value in this case was 0.059, which means a 5.9% chance the the results were due to chance. Just on the border of statistical significance.
So it seems like remdesivir reduces the duration of illness and there’s a possibility that it improves likelihood of dying.
I believe these to be clinically important endpoints.
Time to recovery is not a dumb surrogate marker. It’s important and meaningful to physicians, patients, and the medical system at large.
The death numbers give me optimism as well, even if I’m not ready to pronounce the drug “life-saving” just yet.
What about those caveats you led this email with?
Of course, this doesn’t mean that everyone who gets COVID should immediately be on remdesivir.
When you’re evaluating a clinical trial, it’s important to look at the patient group studied. We don’t have information on the specifics of the patient population yet, so caution needs to be taken.
We also don’t have detailed information on side effects or likelihood of adverse events.
But we do know that it’s going to be expensive. Estimates of “appropriate” pricing for remdesivir have started to come in at a value of around $5,000 per 10 day course.
At a manufacturing cost of around $10, this could mean billions in profit for Gilead.
I’m not going to get into a detailed cost-benefit analysis or discussion of quality adjusted life years, but this cost is worth raising as a point when we discuss the broad application of any medical intervention.
Every doctor wants to ignore cost and just give the patient in front of us any treatment that works, but as a society, unfortunately, cost matters.
Concluding with optimism again
So it looks like remdesivir is going to be a viable treatment option for at least some patients sick with COVID-19.
I’m looking forward to pouring over the data in more detail as it gets released, and I’m sure new insights will be apparent when we’re able to read the paper in full detail.
And it’s a really exciting day for patients that we finally have a treatment that looks like it will speed up recovery.
I’m not ready to declare remdesivir lifesaving, but there’s certainly reason to be hopeful there as well.