Results from an interim analysis of COVID-19 patients receiving Gilead Sciences' (GILD -2.70%) antiviral drug Remdesivir in phase 3 clinical trials conducted by the National Institute of Allergy and Infectious Diseases (NIAID) were announced April 29. They showed that the drug met its primary endpoint in improving patients' recovery, but failed to achieve statistical significance in improving patients' survival.
Does this mean Remdesivir is unable to save lives? Or is there something investors and skeptics have overlooked?
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How do the numbers look?
During an interim analysis, COVID-19 patients who were administered Remdesivir took 11 days to recover, compared with 15 days for patients who were administered the placebo (31% improvement). This was the primary endpoint of the trial, and it was achieved with robust statistical significance.
However, the trial barely missed another endpoint, reduction in mortality rate (the number of patients deceased out of total patients enrolled in a clinical trial cohort). In all, 11.6% of patients in the placebo cohort died, compared with 8% of patients in the Remdesivir cohort. These results barely missed the threshold for statistical significance.
So can Remdesivir save lives?
It's highly likely. Now, readers may be wondering how it is possible for a drug to save patients' lives if a study showed that it doesn't reduce mortality rate. To better understand this, let's brush up on some of the basics of clinical trial design and statistics.
In large, late-stage trials such as this one, the principal investigator (Gilead) will use an independent Data and Safety Monitoring Board (DSMB) to monitor trial progress and make recommendations based on periodic reviews of unblinded data.
If an experimental drug demonstrates efficacy with robust statistical significance and is targeting a condition in dire need of treatment, the DSMB will recommend early termination of the trial and rush the experimental drug to approval.
In the case of Remdesivir, this is exactly what happened. The primary endpoint of the trial was to measure time to recovery, and when it was met, the trial was terminated for outstanding efficacy.
That means one reason the survival benefit didn't pass the statistical test was because the trial did not progress to completion. There have been case studies in which an experimental drug did not exhibit statistical improvement in mortality rates in the early stages, but the DSMB recommended the continuation of the study, and at completion the benefit turned out to be highly statistically significant.
Statistical power can be an issue. If an experimental drug is hypothesized to have a small or moderate benefit to patients' survival, then more patients need to be enrolled in order for the trial to demonstrate statistical significance.
For the sake of argument, if Remdesivir had an actual, absolute survival benefit of 5% (based on the difference between the treatment arm and the control arm), it would be almost impossible to demonstrate this in a study of 20 patients taking Remdesivir or placebo. However, if the study enrolled 2,000 patients -- or 20,000 -- then the benefit will be easily witnessed and deemed highly statistically significant.
I do not think the 1,063 patients enrolled in the NIAID trial were sufficient to determine whether Remdesivir has a small or moderate benefit. However, we do know now that the drug works against the COVID-19 coronavirus, and more likely than not will prove to save lives in larger clinical trials.
Additionally, readers should not be dismayed by a small absolute survival benefit. Again, for the sake of argument, if the mortality rate was 5% for 10,000 COVID-19 patients who took Remdesivir and 10% for 10,000 COVID-19 patients who didn't, then the difference among the two cohorts would amount to 500 lives saved by the treatment.
What about the China study?
At this point, skeptics may object to efficacy claims by referring to another study conducted in China, which determined that Remdesivir showed no survival benefit against placebo.
That study was terminated early due to low enrollment, and it suffers even more strongly from the same statistical power problem. The trial involved just 237 patients, making it even more difficult to show the survival difference between Remdesivir and the placebo. As a result, the data from the larger trial overshadows the results published in this one.
Does this make the stock a buy?
In short, yes. In another article, I discussed the possibility of a second or third wave of COVID-19 infection based on historical precedents for respiratory pandemics, and Remdesivir could help if it is approved in time.
The U.S. Food and Drug Administration (FDA) has begun procedures for emergency advancement of Remdesivir. In addition, NIAID director Dr. Anthony Fauci has claimed the drug is now "the standard of care" for COVID-19. By year's end, Gilead said it will have "millions" of doses of the antiviral therapy stockpiled.
With all that said, a promising catalyst to combat a global pandemic is not the only area of growth in Gilead's pipeline. Recently, the company has greatly expanded its exposure in the field of immuno-oncology with the acquisitions of Forty Seven and Kite Pharma. This is definitely a stock biotech investors do not want to miss.
