Julie Ann Justo, PharmD, infectious diseases clinical pharmacist and assistant professor at the University of South Carolina College of Pharmacy, discusses the treatment potential for remdesivir for SARS-CoV-2, as well as distribution strategies for the drug.
Drug Topics®: Hi, my name is Gabrielle Ientile with Drug Topics® and today we're talking to Dr. Julie Anne Justo, infectious diseases clinical pharmacist and associate professor at the University of South Carolina College of Pharmacy. Today we're talking about remdesivir, 1 of the current authorized treatments for COVID-19. Dr. Justo, thank you so much for joining me today.
Justo: Thank you. It's a pleasure to be here.
Drug Topics®: I'd love to start with a little bit of your professional background and your current day to day during quarantine.
Justo: I'm a trained in infectious diseases as a clinical pharmacist, so that means on a day to day basis, when I'm rounding with infectious diseases physicians in the hospital, we will see patients with a variety of complex infections. For now that includes a fair amount of COVID-19 patients. My job as a clinical pharmacist is really to optimize the pharmaco-therapeutic regimens for each one of these patients, if they need in antimicrobials, for a variety of differential diagnoses, we'll make recommendations for how best to implement. That includes recommendations on dosage, management of drug interactions, management of side effects and how to monitor for efficacy and safety of the agents that we use.
Drug Topics®: So what has made remdesivir a top contender for treating COVID-19 and does the research show efficacy?
Justo: Remdesivir is an interesting compound. Originally, most people will be familiar with it as it was an investigational agent in the treatment of Ebola virus. And remdesivir itself, its purported mechanism of action is a nucleotide analogue that is going to disrupt viral replication at the RNA polymerase. When the virus is inside the human cell and trying to hijack and increase its own replication, remdesivir is theorized to block that replication, starting relatively early on in the disease course of the SARS-CoV-2 virus, and so people were very excited when COVID-19 hit and started to infect patients worldwide because at least in vitro, remdesivir demonstrated very good potency in order to block that viral replication in the lab. Folks started utilizing and investigating remdesivir in human clinical trials. The first of those was in Nebraska under the NIAID clinical trial, which has now been announced just having some preliminary results that are promising, but we're still waiting on a full publication of the study results from that ACTT trial. In addition, remdesivir has many other clinical trials that are ongoing to the ones that also have promising preliminary results are the phase 3 clinical trials that the manufacturer of remdesivir, Gilead Sciences, is actually undertaking. Those 3 trials combined had some very promising results that led to the FDA emergency use authorization (EUA) most recently about a week and a half ago. But again, just to make sure we are cautiously optimistic because we're still waiting on the full trial results of remdesivir to be published.
Drug Topics®: And when would you expect those results to be published?
Justo: Well, hopefully, any day now. We've gotten some word via press releases and other announcements from Gilead Sciences that they are working on releasing the full trial results from their phase three studies, hopefully over the next few weeks. Some might say hopefully by the end of May. Then we're hoping honestly any day now that the NIAID trial results from that ACTT trial will be published, hopefully within again the next few weeks. Clinicians such as myself are really calling for those to be published as soon as possible because we need that information in full in order to design and best allocate the current limited supply of rum destined beer that we have.
Drug Topics®: How does the research findings for this drug compare to hydroxychloroquine, for example, which has been in the news a lot and has been authorized as well?
Justo: The data for the severe clinical trials - again, these are the data that are preliminarily, have come out - they seem to be from better designed studies than the initial positive results that came out from hydroxychloroquine. My personal interpretation, I believe that the remdesivir seems to because the studies are better designed to rule out any potential bias as randomized prospective controlled trials, they seem to be a little bit stronger than if you were just looking at hydroxychloroquine which a lot of the data up until this point has been case series. Case series are going to introduce a lot of potential bias, a lot of times they're open label, and so on. There are difficulties with conducting any clinical research in the midst of a pandemic. We can poke holes in the studies for both hydroxychloroquine and for remdesivir. However, I think the NIAID trial for remdesivir in particular was very well designed and has a hope of getting us some very high quality data, whereas some of the data that has been coming up for hydroxychloroquine. Like I said, initially, the study designs themselves were not very strong. The ones that were better designed that had adequate control groups, unfortunately, the outcomes when you compare hydroxychloroquine to either placebo or other standard of care, or not, borne out in those particular studies. So right now, many clinicians are feeling that remdesivir is more promising at this point than hydroxychloroquine.
Drug Topics®: What are we seeing currently in terms of remdesivir supply and distribution in the US?
Justo: So that has definitely been a hot topic, since the FDA issued their EUA about a week and a half ago. That process has been interesting. Right now there's about 3 different ways that you can get remdesivir. Currently in the United States, the first one which has been long standing, is enrolling your patient in a clinical trial. That's the NIH trial that I talked about a phase 2 trial from Gilead, or so on. The second way to get remdesivir would be through a compassionate use access with Gilead Sciences. That has evolved over time. The inclusion and exclusion criteria have evolved for that over time, and it currently stands as being offered to pregnant patients, or pediatric patients less than 12 years of age, but there are some exclusion criteria even for those specific individuals. That's a very small proportion of folks who are going to get remdesivir through that mechanism. Now the third way, which a lot of folks in different hospitals employed was expanded access protocols, which was a little bit looser criteria. Again, it was drug that was coming from Gilead Sciences, but it was a limited supply. You may get enough shooting courses for, say, 10 patients at your institution.
Now, with the FDA providing this additional mechanism EUA, we're seeing Gilead Sciences sunsetting a lot of those expanded access protocols and shifting that supply to the EUA that the FDA has outlined. Which again, is an attempt to loosen the criteria for patients to be eligible for remdesivir so more people can qualify to get this drug. The hardest part of remdesivir supply right now is the fact that Gilead Sciences as a manufacturer is still ramping up production to meet what is now global demand for treatment of COVID-19, and so the current data that we have is that Gilead Sciences has donated 607,000 viles to the US government for further allocation through HHS to state health departments. Everyone this week is actually in the midst of identifying what their local state process for distribution is going to be. Some states might have 150 treatment courses all together, some states might have as few as 10 or 50 treatment courses. And so you can imagine it's a very limited supply and we're hoping that that will be alleviated by ramping up of manufacturing down the line.
Drug Topics®: Why do you think the government is unclear about this distribution?
Justo: If we just look at prior FDA EUAs, we can kind of compare those processes to the current process with remdesivir. For example, when paramavir was approved a couple of years ago to address the H1N1 pandemic, it was issued EUA. And at the same time, the FDA coordinated to develop a web page that had an online form that a clinician could complete if they felt that they had a patient that was eligible to receive the drug. Unfortunately, when the effects recently issued the EUA for remdesivir, there was no associated mechanism, website, phone line, email, there was no way to request the medication through this supply mechanism from the federal government. That led to a lot of confusion and additional time and sleuthing on a lot of pharmacists parts to try to find ways to access this remdesivir. We knew it was out there, but we didn't necessarily know how to get it or how to advocate for our hospitals to receive some of that allocation. Now fortunately, we fast forward a couple of days and we have a bit more information about how to get it. We've learned since that AmeriSource Bergen is going to be the sole distributor the drug is coming from the donated supply of Gilead, HHS most recently on Saturday released a press announcement stating the amount that they have and that they will be distributing it directly to state health departments, and then those state health departments will provide further information to their localities and health systems that they serve to provide further information on allocation. It is still a very fluid process, but instead of having the process outline on day 1, it seemed to take a couple of days to get that going.
Drug Topics®: And what do you expect to see in the coming weeks in relation to remdesivir being available?
Justo: I'm hopeful. Gilead was aware that their drug was promising, and so they have been discussing their plan to ramp up manufacturing over the next few months going into the end of the calendar year. I am very encouraged that the manufactured supply of remdesivir will increase over the next weeks to months. Whether that will be enough to supply the current demand that is present worldwide and will continue to increase as SARS-CoV-2 spreads internationally is difficult to say. I don't think anybody knows the answer to that question quite yet. There are also some rumblings of potential partnerships that Gilad might be able to have with other manufacturing plants in order to, again, increase production that much faster. That might even include some partnerships with governments around the world. I'm optimistic, but I'm still waiting to see if we will have enough remdesivir to routinely supply. At the same time, I'm also waiting to see the fully published results from these clinical trials because. Like I said, while it's promising, it's certainly not definitive data to conclude efficacy and safety for this agent.
Drug Topics®: And what do you see as the most important takeaways on this topic of remdesivir for treatment and supply?
Justo: I think for pharmacists, the biggest thing to remember is not to lose sight of our original purpose, which is to optimize therapy for our patients. It's very important to understand the background pharmacology of this agent, which is readily available, and the FDA factsheet that's been provided for health care providers. I encourage pharmacists, physicians, and other folks that will be interacting with and using this medication in patients to read that and be familiar with that so that they can properly both dispense the medication, administer the medication, and then also to counsel patients and families. The FDA also issued a fact sheet that's specifically for patients and caregivers. I think it's really important for us as health care providers to read that as well. It's very similar to the type of information that you would find in an informed consent. If we are to use remdesivir in our patients, it is not yet officially FDA approved, it is crucial that we counsel patients on the perceived benefits versus risks with regards to considering use of remdesivir for treatment of COVID-19. Within that conversation we should discuss, okay, what are the potential other options? What are the potential benefits you might expect to receive? What are the potential risks? What are the things that we're going to do to monitor you as you're on this experimental therapy? And then the last thing that I would say is that it's very important that for clinicians that are using this agent, via any mechanism, that they're still reporting any adverse events, particularly serious efforts events, so that we can collate that information at the federal level and also Gilead can hopefully combine that data, and we can learn together how best to use the agent.
Drug Topics®: Those are all the questions that I have. Is there anything else that you wanted to add or touch upon before we wrap up today?
Justo: I just wanted to give a big thank you out to all the pharmacists that are working on the front lines, be it in a hospital setting, community setting, consultant pharmacy, what have you. We know folks are working around the clock to combat COVID-19, and hats off to all of you working out there trying to read about all these experimental therapies is certainly a firehose of information, and I've been extremely proud of our profession of pharmacy and what we have been able to do to provide patients and providers with the necessary information that they need.
Drug Topics®: Dr Justo, thank you so much for sharing your expertise today and your continued work during this time as well. Stay safe.
Justo: You too.