(upbeat music) - Welcome to the ASHP Advantage podcast, Engaging the Experts on ASHP Official, featuring conversations with top level practitioners about the latest issues in pharmacy and healthcare. - Thank you for joining us in this episode of Pharmacy Hot Topics, where we sit down with content matter experts and discuss what is currently top of mind in the world of pharmacy. My name is Mike Ganyo. I'm Senior Director of Pharmacy Practice and Quality at ASHP and I'm joined by our esteemed faculty today, Kathy Yang who is Co-Vicene Clinical Innovation and Entrepreneurship and Professor at UCSF School of Pharmacy and Infectious Disease Pharmacist at UCSF Medical Center, Theraparsans, who is Clinical Pharmacy Specialist, Pediatric Infectious Diseases and Antimicrobial Stewardship Co-Lead at the Children's Hospital of the King's Daughter in Norfolk, Virginia, and Monica Mahoney, Clinical Pharmacy Specialist Infectious Diseases at Beth Israel Deaconess Medical Center in Boston, Massachusetts. Today's episode is part of the ASHP Advantage Podcast Series, Engaging the Experts, featuring conversations with top level practitioners. Please note that this episode is sponsored by AstraZeneca and is for informational purposes only, it is not approved for continuing education credit. Kathy, Monica, Sarah, thank you for joining us today. Let's get started on today's topic, COVID-19. Kathy, you've been doing a great job keeping us updated with the current state of COVID variants, any vaccination statistics. Can you kick us off with the current status of COVID-19? - Yeah, thanks, Mike. And it's so nice to be back with the crew. I miss this group every time we don't see each other. So the environment, we're in the summer. So COVID is low. Test positivity's are slightly starting to bump a little bit, but overall in the grand scheme of things, we're still pretty low in terms of test positivity's and ER visits, hospitalization and death, which are the severity indicators that CDC looks at, seem to indicate that there is no change in those. So those are the good news. We have to always, of course, be on our toes a little bit, because since the start of the pandemic, we have always seen a winter surge and a summer bump. I don't want to call it a summer surge, because it's never quite as dramatic as the winter. But we will see a little bit of a wave, and that's been consistent all the way through for the pandemic. So that's just something we should pay attention to. With regards to variants, we have this new variant that has been sort of making a lot of headlines lately. And if you remember, we're all, of course, all in on a crayon, and we had this J&DOT1 variant for a long time. And now it's slowly being overtaken by this other Omocron variant, which is called KP.2. This is also a sort of sub lineage off of the J&DOT1. And this is starting to make people a little bit nervous, because it does have this thing called the flirt mutation. You've been starting to hear that term now in the news a lot. It has nothing to do with Taylor Swift, Monica. So it is basically two different mutations. One, the FL part of the flirt is F-456L, basically the F replaces the L. And this is a mutation on the receptor binding domain. And the reason that's important is because it makes the binding more tight and it decreases any type of monoclonal antibody or immune binding. Then you have the other one, which is this RT part of the flirt. That's the three, four, 50, 16 mutation. And that's on the N terminus. And the reason that's important is that part of the virus is important for viral entry. So you get increased viral entry and a little bit more immune evasion. So that's the thing that's concerning about flirt and something that we should be paying attention to over the summer. Right now it's at about 28.5%, but we should expect it to start going up. - Yep, and as expected every mutation seems to provide some increased advantage over previous mutations and we can just expect this to continue as a, that advantage obviously naturally selects and we'll continue to have to manage them. - I missed the one most important point about this. Even though it does have an ability sort of the escape immunity and it's more transmissible, the good, good news about this is it doesn't make people more sick. So it's not more virulent. So expect more of this sort of low level infections and kind of the upper respiratory type infections for healthy immune people. And of course we always have to be careful about the people who are immune compromised. - Yeah, and I think we'll get, we'll get to the immune compromised here in a second, but I, when you broke in there for a second, I thought you were going to correct yourself 'cause clearly everything has something to do with Taylor Swift to Monica. I mean, there's no exception there. She'll be in her background right now. - I was going to say for our listeners, you can't see we're on a video Zoom call in my background is the Aeros Tour opening curtains. - Now we need a flirt tour. (laughing) Okay, so last time we talked, Pumipa Bart was brand new. We got a brief lesson on WHN, the only clature for clonals. So it's been a little bit of time. Has there been any news on implementation of Pumipa Bart challenges? We know there was going to be some cost associated with it. What do we know about the use of Pumipa Bart? - So before we get to that part, which I'm going to hand over to Sarah, I thought I would first tell you about some of the preliminary results that came out over the last few weeks. So this study, of course, was based on the canopy study. And there are bits and pieces of it that have been recently published at different meetings. So the first one was at the American Transplant Congress. And the second one was at the American Society of Clinical Oncology. These were just actually literally this week. So late May and actually early June, I think ASCO ends today and I think ATC ends tomorrow. So they did have a couple of posters looking at the looking at Pumipa Bart in either solid organ transplant patients or solid tumor and hemoligants lead patients. And just to sort of give you the top line on this, basically this again has no clinical data. This is all immune bridging data. And looking at immune bridging data, it all looks like it works so far. The thing that I found really interesting about these two studies is they actually look at underlying immunity of these two patients populations. And it turns out that 97% of the patients in the solid organ transplant population and 98% of the malignancy population all actually had spike protein antibodies, meaning that the vaccine actually took. So that was good. They all had multiple vaccines, at least five, I think was the median. And the thing that was most interesting to me was the incidence of treatment associated adverse events was high for both population. It was 52% about for both of them. And for grade three AEs, it was consistent at about 9%. So again, that's something we will have to pay attention to when we use the drug. - So use of MIVART and pediatrics has been challenging for multiple reasons. As we kind of discussed earlier where the odd population where ion injections, especially within our immunocompromised populations that already have established IV access, intravenous is actually a better option because of the fear of ion injections. And because our pediatric patients have to get so many all the time, anyway, that sometimes it may actually have better, there may be better utility of an injection or intravenous injection. However, because of all of the significant barriers with cost and with changes from things no longer being free for the treatment of COVID-19, we have had some significant issues with figuring out how we're gonna utilize it within what population and where. Because as we discussed on our previous podcast, this is after the infusion, you have to monitor for two hours. So this is going to be a significant time requirement for our outpatient infusion centers if we're utilizing it on an outpatient basis and for staff and demand in an already very busy environment. So that's problem number one. Problem number two is if you were to capture this and utilize it inpatient where you already have them and you could just do like every 15 minute vitals after you utilize it within that group, it's not bundled into billing and it is around $6,000. So even if patients do, so from the inpatient side, that would be a cost the hospital would eat. And I know a lot of institutions are not going to be able to handle that. If we're gonna do it on an outpatient basis, although you're going to have coverage from medical insurance, you are still looking at a copay of, I think the one patient we were trying to determine is we were gonna utilize it in was around $400. And so if you were looking at risk and benefits at the current moment with the rates of positivity and the rates of hospitalization from severe COVID, which are thankfully low, it's kind of, it's something that they just feel like is not worth utilizing. And also a few factor in the fact that during the trials, even though they were open for children greater or equal to 12 years of age and 40 kilos, they weren't really included. I don't think, unless something has changed, there hadn't been any children less than 18 years of age that were included in the analysis, which is not abnormal. We do this with other drugs where we extrapolate based off body habitus and metabolism, et cetera to the population of greater than 12 and greater than 40 kilos. So it's not that it's unsafe, but it's a little unsettling, I think, for a lot of families and for some pediatric providers when they read that. And if you put that in the context, also of the 0.6% rate of anaphylaxis, it tends to make people very nervous. And hence has not led to us utilizing it actually at all within our institution. And I think minimally across the field of pediatrics. And then, when you think about what other options start on the horizon, you do have to think about Sipamivabart, which is a long-acting antibody that is now in studies that has shown a statistically significant decrease in the incidence of symptomatic COVID versus controls in the immunocompromous population. It is intramuscular. And children in the trials greater than 12 years of age and greater than 40 kilos have been included. However, I don't think there have been any that have actually been, it's been utilized in. And I think there's more to come in that in the future. And I know Kathy is going to talk a little bit about that as well. But if we think about equitable access to this and how we ensure that we're utilizing this within all of our populations equally, I think, one, with Komivabart, we haven't been utilizing at all. And I think that this is going to be something that we really have to consider, should this drug become approved in the future as well? - Yeah, thanks for bringing up Sipamivart. I think there's some anticipation that we'll see movement on the authorization of that sometime this summer. Kathy, anything from an adult population there, any anything you want to share? - Yeah, so for Komivabart, I think we're pretty much in the same place that Sarah is with Pete's. The 9% infusion reaction rate and the 0.6 anaphylaxis is actually something we've talked about in quite some detail. We are trying to see if we can set this up to do a limited number of patients in our outpatient infusion clinic, but because it's going to take so long to infuse and there's the observation time, there's also the cost. This is going to be a pretty long process for us. We have to do some pretty significant counseling with our patients about cost, so financial counseling as well as doing prior authorizations before we get them into clinic. And we were thinking, if we do 10 patients a week and there's a 9% infusion reaction rate, that's almost one patient a week. So we will do pre-medication. We're trying to make sure we're doing it safely. So that's all in the works. It's of course takes a long time to do. And unlike during the pandemic when everything had to have been done yesterday, this is not as emergent because of the state of COVID. And we do have good therapeutics. So we'll get it done when we get it done. - Also, Kathy, I was going to ask you if you, because of that rate and you're thinking about how to do it safely, if you look at the actual incidence of hospitalizations and that rate of infusion reactions and anaphylaxis, if you look at risk and benefits, it kind of gets a little bit more gray. - Oh, it's absolutely gray. So it's risk benefit and cost, right? So is the juice worth the squeeze? - And, you know, these are long conversations. We're not going to do it on the inpatient. That clearly, it sounds attractive because you have a captive audience, but at the same time that it's so expensive, you know, it's not part of the transplant bundle. How would we pay for that? So we've had lots of conversations about it. Is the juice worth the squeeze? We don't know. I'm sure this is something that over time, you know, keeps changing. So we just keep evaluating as we go. - Yeah, and I mean, our rate of, if you look at the population and within peaks that we utilize it right now, as of June 3rd, between 12 and 17 years of age, the rate of hospitalizations was like 0.1 per 100,000. So, and that's the risk of, you know, severe COVID. So if you look at what we're trying to prevent versus what the potential risks are, I think that is where people are getting very hesitant. And I think that's why, especially in pediatrics, we're seeing like, right, you know, apprehension. - Yeah, and, you know, when we get towards the winter months, that of course might change as we see more COVID. So, you know, always looking forward with our eyes right open in terms of trying to guess what's gonna happen next. I think we are sort of looking forward to seeing the data on Sephavabart. Like you mentioned, that one does have clinical data, AstraZeneca released some top line data, I think it was in mid-May, where they basically showed that it met their primary endpoints against variants that had the F-456L mutation, as well as ones that did, variants that did not. And that's actually really interesting data, because Sephavart is not supposed to have active variants for 56L mutations. So the fact that they still met their primary endpoint, I think is very exciting and interesting. I think we'll have to see what the actual data looks like, but that one, if they, you know, everyone's anticipating, when is that gonna come out? If it's IM, that would be awesome for the adult population. I know you don't like that for the peeves, but for us, that's way easier. So we know that it doesn't have the infusion reaction rates that November does, so that's the other part that's exciting, we look forward to. - And that will certainly be helpful. And I anticipated we would have more IV utilization within that population. And we may actually have more utilization with the intramuscular, but I know the largest barrier we had previously is, you know, we have vaccination rates within this population of less than 20%. So just trying to push, get vaccinated, also get boosters, and now get this other injection is just very challenging. So I don't think, I think there's certainly issues with both intravenous and intramuscular, but I think having to push so many vaccines, especially within the pediatric population, has made this intramuscular utilization so much more difficult. - And we, our normal sequence has been to talk about the state of things, vaccines, and then go into the preventive, which of course, there's not been a lot of news on the vaccine lately, and there has been news on these pre-exposure prophylaxis medications, but for our listeners benefit, this week, the FDA advisory committee is actually meeting to talk about what will be in the fall update to the COVID-19 vaccine. So I have to imagine that the mutations that Kathy discussed earlier in the podcast will be included in what we would anticipate this fall, the updated COVID vaccine, what we'll see, we'll see what the advisory committee decides. So the next thing that we usually cover in our sequence is treatment. And I don't know that there's been a lot of treatment news, although one of the major things, the major items recently, I guess in last year or so was Paxilbid, but yeah, we have full FDA approval, and that has opened up the potential for off-label use. Monica, I'll let you take over, what would you like to share on treatment, particularly with their Matravir, Tritonavir, and Matravir, I give up. - Don't worry, I slaughtered my initial attempt earlier of saying a word that I've said multiple times, so. - Our four-year journey with these presentations and podcasts are going to be over, and then like three weeks later, Mike's going to be able to pronounce the generic medication name. - Yeah, never. - Before I get to talking to Neumachery Ratonavir, I want to take a step back about vaccine. So I've been attending various pharmacy or ID-related conferences going to speak with the vendors and the different manufacturers, and the question that I've been asking them about these vaccines is when they're getting a combo vaccine. Yes, Mike talked about, we're going to have possibly updated composition or what's going to be the formulation that goes into what variants, but I also want a combo. I want COVID and flu plus or minus RSV, and I know that Sarah for her pediatric patients as well, I don't think we're getting it this season, but in the horizon, in the future, maybe we can come back and do another podcast on that. - Yeah, I know, as of a couple of years ago, Moderna was looking at that. I don't know if they, I don't know what the status is, maybe you learned something, but I'm kind of surprised this. There wouldn't be a candidate this fall, but perhaps they're doing their trials still. - I heard there was going to be a, it was not going to be on the horizon for this upcoming fall a bit back, because trust me, I have been really persistent about asking those questions, 'cause I really don't like giving multiple injections to these small children, which is right now, I'm like, hey, come to pediatrics, come to your appointments, and then we give them seven injections. So I'd really like to minimize that if possible, but I was told that this fall probably wasn't going to. - And let's be honest, we also don't want to wear patients. - Yes, I love having to get these one on each arm. So although one exciting thing I will say not to make the topic about flu, but if it is an mRNA vaccine, you finally have a candidate for patients who have that egg allergy that might have the country indication to the current flu vaccines. So that'll be an exciting development if and when that comes along. - And if we really shoot for the stars, I can't wait until we have all this as nasal vaccines, that they actually work, and we don't have to do shots anymore. I mean, they work better as nasal anyway. - Well, that last part is key has to be a higher efficacy, but this is a COVID podcast team. So let's get back. Let's stop flirting with flu, if you will. Okay, no matter if you're a baton over here. So yeah, it's been commercialized. I think that makes clinical acquisition for the pharmacy easier because you don't have to go through possibly convoluted ways of ordering the medication since it is commercially available. On the flip side, that means that patients may be subjected to a high cost or co-pay issues. A lot of the rules and regulations are expiring so patients may actually have costs associated with getting the medication. Particularly for our immunocompromised patients, there has been discussion and interest in using longer durations of therapy, of course, off-label FDA approved for twice a day dosing for five days. However, there have been manufacturer initiated investigations looking at longer durations for our patients with immunocompromised. I might have mentioned that on one of our previous talks, what's called EPIC IC, EPIC immunocompromised. Essentially, it was taking patients with immunocompromised and randomized in COVID and randomizing them to the receipt of either five, 10 or 15 days of nurmetria or tannabere in the primary endpoint was a decrease of viral loads to less than 100 copies per ML at pre-specified durations. We can argue on whether that threshold has clinical meaning or not, but for objective endpoints, that is what the study was designed to look at. I think really nice is that they also did a subset analysis of patients that had severe immunocompromised and they defined that clearly. And so not published yet, however, presented as a poster at CROI. It is available online if you go to the manufacturer. And 10,000 foot view of the results, there was no difference in the overall population in terms of decrease of viral load to less than 100 copies per ML. If you looked at five versus 10 versus 15 days of therapy. However, if you looked at the severely immunocompromised patient, it did look like there was a difference. Patients with severe immunocompromised, they still had detectable viral loads above that threshold of 100 MLs, 100 copies per ML, apologies. After that five day period, versus patients who received the medication for 10 and 15 days were not detectable. So if you tease it out for severely immunocompromised patients, maybe there is a benefit for going for longer, could not tell between 10 or 15 days. So on the basis of that poster that was presented at CROI, some of our clinicians are looking to use longer durations of therapy in our patients with immunocompromised and we actually had a couple of those patients. The issues that we're running into is that, yes, this is FDA approved medication, you can use it off-label, insurances might not cover the off-label indications, they may not cover that longer duration. So we've had a couple of instances where clinicians determined it was in the best interest to treat for maybe a 10 day course, prescribed it for the patient, the first five days are approved, no copay for the patient, and then patients get faced with really high copays for that second five day course. I've heard of patients paying on the pocket, $14, $1,500 for it, looking to get reimbursed and we're like, we don't know what to do. The best thing is don't pick up the medication 'cause don't pay the money, let us try to figure out different ways of coverage first. We've previously talked about Paxis, so it is the program to try to get the medication covered, the caveats there is that they usually only cover the FDA labeled dosing, additionally this additional coverage expires at the end of this year unless it is extended. So I've had the distinct honor and privilege of writing appeal letters to insurance companies to try to get these longer durations covered, they have been successful, it's a pain, but it is something that we can provide a service we can provide to our clinicians. Basically, very generically outlined why the patient is immunocompromised, what their previous course with COVID has been, when have they been personally positive, give the dates, give the thresholds, et cetera, I just dump a lot of information and then quote the primary literature. So I know that it isn't evolving, but there are some case series and reports out there of patients with immunocompromised receiving these longer durations, put the citations in there. If you're interested, you can contact me, I can send you those citations. Also quote this clinical trial that is available on clinicaltrials.gov, but results haven't been posted online yet. And we have been able to successfully get the medication covered for the patient prior to the call Kathy asks, well, how do you actually dispense it? It comes in a box or a kit of five days and we're like, yeah, it's a Wild West when it comes to this. We tried this in the prescription for the 60 tablets, which is the 10 day course, all this messaging to the pharmacist saying, yes, we're intentionally trying to prescribe a longer duration, you know, possibly call the pharmacy as well to be like, hey, wanna make sure you saw that? No, we want to dispense 10 days. We've had other patients that it's been fragmented where they fill a five day supply through their insurance and get the normal course and the second prescription goes out for that second five days and that's when the prior authorization kicks in. It can be a hot mess. I am thankful that we have pharmacy technicians that work with me to deal with the insurance companies and their approval and whatnot. So that's some of the outpatient stuff we've been dealing with in terms of treatment, Mike. Thanks. Well, for anyone else who is following other treatment options, the PMIVA BART, actually the manufacturer of that product has released the press release, saying that they intend to file for treatment as well. So that may be on the horizon. I know there's been talk in the past of oral forms of remdesivir, haven't seen a lot of movement on some of these other potential treatments, but we'll keep everyone posted if we learn more. I think that brings us to our conclusion. So I wanna thank everyone today. We got an update on the state of things and learned a little bit about the flirt mutation in our most recent variants. Some new options, well, one recently available, one pending availability for pre-exposure prophylaxis. And thank you, Monica, for some of your personal experiences with off-label use of your matriever to forget it. - Oh, close, so close. - It is not close, but thank you. Well, that's all the time we have for today. Once again, I just have so much fun with this group. So thank you, Kathy, Monica, Sarah for your time today throughout this whole series, it's been a blast. And we hope you enjoyed today's conversation. Be sure to subscribe to ASHP Podcasts, through your favorite podcast provider. Take care. (upbeat music) - Thanks for joining us for the ASHP Advantage podcast, engaging the experts. Be sure to visit ashp.org/podcast to discover more great episodes, access, show notes, and download the episode transcript. If you loved the episode and want to hear more, be sure to subscribe, rate, or leave a comment. Join us next time for more expert perspectives on ASHP official. (upbeat music)
