Julie Ann Justo, infectious diseases clinical pharmacist and associate professor at the University of South Carolina College of Pharmacy, discusses the latest data from Gilead's trials for Remdesivir, a potential COVID-19 treatment.
Drug Topics®: Hi, this is Gabrielle Ientile with Drug Topics®. Today I'm going to be interviewing Dr. Julie Ann Justo, infectious disease clinical pharmacist and associate professor at the University of South Carolina College of Pharmacy.
And our last interview, Dr. Justo highlighted some of the preliminary results supporting remdesivir as a potential treatment for COVID-19. Since then, Gilead has announced their latest phase 3 SIMPLE trial results, and Dr. Justo joins again to provide expertise on this data.
Drug Topics®: Dr. Justo, thank you so much for joining me again today to give us an update on the remdesivir trials.
Justo: Hello, it's my pleasure.
Drug Topics®: So last time, you described some of the more preliminary data surrounding remdesivir as a potential COVID-19 treatment. Can you give us a little review on that data that you told us before we get into the updated trial results?
Justo: Absolutely. I believe the last time that we spoke, we had preliminary findings in primarily press release form that announced the ACTT-1 trial results. That's a study that's sponsored by the NIH. And then we also had preliminary positive results from the Gilead phase 3 SIMPLE trial, which was based on severe patients. Since we last spoke, both of those trials have been published in full, and so we've had a chance to read them in detail and analyze all the different enrollment, what patients were in the trial, different subgroup analyses, and so on. We have a lot more information now than we did a few weeks ago.
Drug Topics®: Can you give us a little update on the Gilead severe trial?
Justo: Absolutely. So, again, we had a simple trial that looked at severe adult hospitalized patients that had oxygen saturations less than or equal to 94% or were requiring oxygen supplement form. That's the definition of severe COVID-19 as they described it in the trial.
What they did was they actually looked at patients that were randomized to receive remdesivir either 5 days versus 10 days in that severe trial. It was important to note there was no placebo controlled arm for that particular study, and the main question that Gilead was trying to answer designing this trial was figuring out if 5 days of therapy had the same efficacy as10 days and that's really important because if so, if five days is comparable to 10, and that could extend the limited resource of our industry supply that we currently have available. What the study found was that for their primary endpoint of clinical improvement at day 14, and that they had similar outcomes in the 5 days versus 10 days in terms of odds of reaching that clinical improvement threshold for their patients, which was very positive findings, and encouraging for a lot of us who are trying to make the limited supply of remdesivir stretch to as many patients as possible.
Drug Topics®: With these updated trial results, what do you see in in upcoming weeks related to remdesivir supplies being allocated to hospitals?
Justo: I think there was a lot of details. The first thing that we noted when the full trial results were published that we didn't have the last time that you and I spoke was that we noticed the randomization wasn't fully balanced between the 2 treatment arms. Randomization is intending to balance the 5 day arm versus the 10 day arm on all the different baseline characteristics and other potential confounders both measured and unmeasured, that might impact the chances of clinical outcomes for these patients.
What we found, which we didn't know before, was that the 10 day group, again, this is a study of nearly 400 patients, the 10 days group was more severely ill at baseline, and that's based on the score that they received on that ordinal scale when they were enrolled in the trial. And that's very important, because while the study investigators did try to adjust for this baseline difference, it's not 100% clear if they were effective in doing so. We think that the 5 days is just as good as the 10 days and I think we can glean that information from the trial, but we also have to take into account that we're not entirely sure what happened with the patients in the 10 day group because they started in a clinically worse position.
In addition, if we're looking at the study results when we look at the details, about 86% of patients in the 5 day run of remdesivir completed the full 5 days of remdesivir. Whereas at the point of analysis, only 44% of the patients in the 10 day group completed the full 10 days of remdesivir that was intended. Now that sounds like a big difference, which it is. The main drivers are understandable when you look at the way the trial was designed.
These investigators are pressed to get these analyses out as quickly as they can, because everyone is wondering the results of the trial. But what that results in is that in the 10 day arm, a lot of the patients at that point had either been discharged from the hospital or had died. For whatever reason, they didn't complete a full 10 days of remdesivir therapy. Some patients may have received 6 or 7 or 8 or 9 or 10 days.
In addition, there's another important piece of information that we found. We found that they did an analysis where they looked at where were folks at the point of day 5 remdesivir therapy, and then the group versus the 10 day group, you would notice that the 10 day group, if you were at day 5, were on invasive mechanical ventilation.
Okay, so let me take a step back. For the patients that were enrolled in this trial, mechanical ventilation at baseline was an exclusion. However, if they started off not on mechanical ventilation, but met the definition of severe, and then progressed to mechanical ventilation by day of remdesivir therapy, they were allowed to stay in the trial.
If we look at that interesting, small, but severely ill subgroup of patients, what we found is that patients on 5 days of remdesivir, about 40% of those patients that were on mechanical ventilation at day 5, and that ended up dying versus 17% of the patients in the 10 day group and then ended up dying so 40% death versus 7%. Those numbers are small, and it's just a numerical difference; however, that's enough information for a lot of clinicians at this point of time to suggest for patients that are mechanically ventilated on remdesivir they probably need to have consideration for extension from 5 days to 10 days of therapy. So that's an important thing that we learned from the full published trial results in the severe trial. So again, just to summarize, patients that are mechanically ventilated with severe COVID-19 10 days may be better for them than 5 days. That's a lot of where that information came out in the FDA emergency use authorization (EUA) that had that recommendation for 10 days duration of therapy specifically for patients on mechanical ventilation.
Drug Topics®: Do you believe that they're going to continue to pursue this since it was a small population?
Justo: It's very difficult to say if you look at the main drivers of clinical outcomes across all the studies that we have to date, so I'm talking about the 1 trial from the NIH, and the Gilead remdesivir trial, and now we have a new press release from Gilead that talks about preliminary results from the SIMPLE moderate trial, which is patients that have oxygen saturations above 94%.
If you're looking at all this data, in summary, what it's suggesting is that remdesivir does the best for patients that are early in their hospital admission, and not yet to the point where they're requiring life support care in the form of mechanical ventilation, or other things.
Taking that into account, I'm still interested in some further information about whether or not remdesivir will provide any help for patients with mechanical ventilation. As I suggested, there are some limitations to how they’ve designed the study. We also have only just been looking at remdesivir in monotherapy form right now. A lot of clinicians are very interested in seeing how remdesivir could help even more severely ill patients like mechanically ventilated folks, if it's used in combination with other agents such as convalescent plasma, or immunotherapies, such as tocilizumab, all agents that are currently being considered as experimental agents in actual bedside situations.
Drug Topics®: Dr. Justo, thank you so much for joining me again and your continued work as well.
Justo: It was my pleasure.
Editor's note: This interview transcription has been lightly edited for style and clarity.
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