Town Hall: Remdesivir studies

[Joe Guglielmo]
Good afternoon, and welcome to the weekly School of Pharmacy Town Hall Meeting. Before I start, I want to remind you on some of the specifics on how to ask questions and to participate. Your audio and video will be automatically muted. Only the panelists can unmute themselves. The chat function is disabled. And as before all questions, you should use your Q&A feature at the bottom of your screen. As always, we'll try to answer all questions that we can, you can start giving them as soon as we start here. But any outstanding questions will be answered in email, or if anonymous, we'll do our best to answer it at the beginning of the next town hall meeting.

[Joe Guglielmo]
So this is our seventh full week of shelter at home. You all know well the pandemic is still with us, but maybe a few statistics to kind of remind you where we started and where we are. The very first confirmed reporting case in the US was January 21st. We may find out with additional analyses it might have been a lot earlier than that. But at the moment, that was the first confirmed reported case. Now, little than 100 days later, the US has topped 1 million reported cases. And as of 1:30pm today, there were 62,444 confirmed COVID-19 deaths in the United States. In California, to remind you, last week, there were a total of 37,950 cases and 1,447 deaths. As of today, there are 48,870 cases, so it increased by about 10,000. And, and we're up to 1,982 deaths. If you take the usual predictor from the University of Washington, recall last week, they said, as of August 4, they projected the peak total death would be 1,719. As of today, they now estimate that to be 2,104.

[Joe Guglielmo]
From a UCSF standpoint, you may remember last week, we had 14 patients in acute care. And that included our first child, who was a two week old neonate at Benioff Children's Hospital in Oakland. As of the 27th, so just a few days ago, we had 15 confirmed COVID patients at UCSF Health and at that time, several were in the ICU, three of whom were being ventilated, two patients were pediatric while the rest were adults. Of 64 hospitalized COVID patients to date, 45 of them have been discharged from the hospital, two have died. As of 12 noon today, there are now 17 cases at UCSF.

[Joe Guglielmo]
From a state standpoint, you're aware, as of April 19, nursing homes now are required to report COVID-19 cases directly to the CDC for tracking. They were already required to report to state and local health officials but that will be interesting to see how that changes the total numbers. There are also some changes from the CDC as to what are considered to be symptoms consistent with COVID-19. You may remember there were three originally and they included fever, cough, and shortness of breath. They have now added six new symptoms, which include chills, repeated shaking with chills, muscle pain, headache, sore throat, and new loss of smell or taste. I want to remind you at this point, while we're very interested in testing, and vaccines, and potential therapies, this is really not the time to be complacent about what we know does work, and that is really the shelter in place. And when you cannot have shelter in place to wash your hands with soap and water, practice physical distancing, wear a mask, cover your mouth when you cough and sneeze, clean and disinfect surfaces. Regardless of what some say, please do not ever treat yourself with chemical disinfectants by any route.

[Joe Guglielmo]
I would also make you aware. Two days ago the governor announced a four phase, what he calls "resilience roadmap" to reopen the state. I'm not going to restate those, you can look those up if you would like. I only mention that because it somewhat mimics what the campus now is going to try to do as we phase in to come back to work. You all received the Chancellor's April 24 letter, which has been shared, and you should be aware that the focus on the town hall this Friday, May 1, from 4 to 5pm, will be that resiliency plan, how we're going to try to return to work. To that end I mentioned last week but I'll give you a little bit more. It is a three phase plan. Phase One is from now until June. This has been overseen by Mark Freiburg, who is the director of environmental health and safety, and it really mimics the mandates of the city and county of San Francisco as well as the governor's recommendations as well. I don't think there's anything particularly stunning there.

[Joe Guglielmo]
However, in what is called the medium term, what they call resiliency plan, that is being overseen by John Giacomi. And that will start in July and go through December. I think this is the time you're going to see true return to work. What he volunteered there, this is nothing in writing, you can expect, in general, he used the term, a "one-eighth plan" is what he called it. And if you were to take, for example, the wet lab research arena, to use this one-eighth philosophy, one might think of it in the following way. And that is if you had eight chairs at a bench, that means to start off, they will only allow one of those chairs at the bench to be filled and gradually go from there. Then the third, which is more of a long term, would begin January of next year and extend as long as it needs to take place.

[Joe Guglielmo]
There were some outstanding questions from last week. One was, and I'll read it verbatim, but I know the person who's going to answer this is going to give a little more broad of an answer. The question was, can you please involve the student body? And they didn't define what they meant by student body, but student body in the decision making for the protocol for the reopening of labs. And I've asked the Associate Dean of Research in the School of Pharmacy and that's Andrej Sali, to answer that question as best he could. Andrej.

[Andrej Sali]
Thank you, Joe. So I'm going to presume it's a graduate student as opposed to a pharmacy student asking, and I think it's a good opportunity to give you some unofficial information. Things are changing in the background quite rapidly and I will simply summarize what I've seen happening without, please, taking me up on my word here. So, first of all this policy is being prepared UCSF wide. It's not an SOP only issue. And in fact, there's a committee that's chaired by David Morgan who's the Vice Dean for Research for the School of Medicine. It includes, I think, eight other very senior scientists, including actually Tejal Desai and Tanja Kortemme from our school, as well as other senior scientists, and they prepared a draft document that will guide return to research in labs. The first phase, and there will be three phases in all likelihood, may begin as soon as in a week or two, although that is again, very informal, my interpretation, the guidelines may change. And as Joe mentioned, assign one scientist per eight seats for two shifts, maybe three shifts a day, to increase the total number of people who can go back. There are the usual guidelines that you might expect on wearing masks, wiping, social distancing, use of kitchens and bathrooms and so on. And no doubt there will be a need to refine the guidelines based on feedback from anyone. And as far as I can tell that there certainly is a commitment to learn from the feedback from everyone including students, postdocs and others, and react as nimbly as possible. So that's what I have to say, on this point at this point.

[Joe Guglielmo]
Thank you, Andrej. The next question from last week was the following. And that is, are there currently any methods for recovered COVID patients to make directed plasma donations to specific COVID positive patients, eg., family members? Well, part of this I can't answer, a part I cannot, but I think I know the answer. You can, in fact, donate plasma. And in fact, you can do it at Zuckerberg San Francisco General among other places, and they would confirm that in fact you have antibody and it could potentially be used as convalescent serum to help treat certain patients. What I am certain does not exist, however, is the way the question was worded, is whether or not an individual can make directed plasma donations to specific COVID positive patients. In light of the fact we do not yet know, if convalescent serum works to, in fact, improve outcomes associated with infection, it would seem highly unlikely they would be allowed that someone could mandate that their specific serum could be given to a specific patient, unlike what takes place with blood donations at times.

[Joe Guglielmo]
The last question before we move into our special feature in this town hall is the following. I'll read verbatim again. I've heard a lot of rumors that you can reuse N95 masks if they are treated with steam baths. Is this at all credible? What I can tell you is I don't know about steam baths. But I will say if you go to the CDC, they will say that yes, there is some science behind this, that steam treatment is the word they use, can in fact sterilize these masks. And even microwave associated steam treatment is a possibility, it appears to maintain the integrity of the mask for reuse. Obviously, this would be a secondary measure. The real hope is that we can be using new N95s and not really have to deal with it, but that for those that are interested in that, you can go straight to the CDC and they have a very nice section talking about reuse and specifically steam treatment.

[Joe Guglielmo]
I now would like to shift gears, all questions will be at the very end of the 30 minute presentation. And I'd like to introduce Dr. Kathy Yang, a professor and infectious diseases pharmacist in the Department of Clinical Pharmacy in the School of Pharmacy. Dr. Yang has participated in numerous UCSF studies as it relates to antiviral medications, including remdesivir, which has recently as of yesterday, received quite a bit of play, some of some more favorable than others. I also want to point out that Dr. Yang, along with Katherine Gruenberg, Tram Cat and Jen Cocohoba. I want to highlight them among a group of ID and critical care pharmacists who generously volunteered to staff Clinical Pharmacy services for critically ill COVID patients at the St. Francis facility that was created by all the hospitals. That contribution is currently on hold, but we are ready and needed, if expected, with what we think will be a fall and winter surge. I'd now like to turn this over to Grant Burningham, the School's editorial director who will interview Dr. Yang. Grant.

[Grant Burningham]
Thank you, Joe. Yeah, as Joe mentioned, we are really lucky to have Kathy Yang talking about an item which has been in the news and on a lot of our minds lately. She's been involved with the trial of remdesivir. And that was the drug that Dr. Fauci and President Trump talked about yesterday at the press conference. Kathy, are you there?

[Kathy Yang]
Yep. Can you hear me?

[Grant Burningham]
Yeah, absolutely. Again, thank you for talking to us. Let's start with the latest news and what happened yesterday and today. You're involved in the remdesivir trial, and I'm wondering what you can tell us about what we know about the data at this point.

[Kathy Yang]
Yeah, so um, first of all, this trial at UCSF is the NIH one that was being that is in the news and that is ... the PI for that is Annie Luetkemeyer and Sarah Doernberg. And before we get started, I just have to give credit where credit is due and that is really our Investigational Drug pharmacist who is I always think of her as an ID pharmacist, too, because she trained with us, Yelena Koplowicz. So she really runs the show for us. But basically the news that came out yesterday, there was actually a bunch of news. One was the, the China study that was initially leaked last week that showed there was benefit. And that was because the study was underpowered. And at the same time, Gilead had released information on 10 days of remdesivir pretty, pretty much the same efficacy as five days, meaning that you can have shorter days of treatment. And then of course, the big news was the NIH adaptive trial, which is going on here. And in that those results, it showed that there was benefit, there was a shortening of time to clinical improvement that was statistically significant. And so that was the big news that came out yesterday from the NIH.

[Grant Burningham]
So the study yesterday said that there was a reduction in the infection of about four days for people who took this drug. That seems important, but not exactly a magic bullet or a cure.

[Kathy Yang]
Yeah, you know, I think that the data was very promising. It's still preliminary. And it's, I think we still need to see really what it means when all the data is looked at. I think with any antiviral, it's just true that the sooner you start therapy, the better. So that type of data needs to be parsed out still. And so we can see really, who are the ones that truly benefit from the drug. It's very promising. It's very exciting. But like every drug that comes out, we have to just wait till the full data comes out.

[Grant Burningham]
If one of us were to end up in the hospital right now, what is the odds that we would end up on one of these drugs or remdesivir?

[Kathy Yang]
Yeah, so at UCSF, there's actually three different ways you could potentially get remdesivir, one is through the clinical trial. And the part that just finished which this, this dataset came from was a, was a double blinded, placebo controlled trial. So there is always the possibility that you would not get that remdesivir. Gilead also has a compassionate use program for, and an expanded access program, for patients who don't qualify for the clinical trial. And basically what those are, they are open label studies, meaning it's not randomized. There's no placebo. If you qualify, you can get drug. And those are mainly studies for patients who don't qualify for the RCT (randomized control trial) for the adaptive trial for various reasons. So there are other mechanisms to get drug and those include pediatrics, adolescence and pregnancy as well.

[Grant Burningham]
Can you tell us a little bit about the history of remdesivir?

[Kathy Yang]
Yeah, so this was a drug that is actually probably about 10 years old at least. It was developed by Gilead, initially, I think even before Ebola it might have been looked at for Hep C. But the big studies for remdesivir really for Ebola when that was big a few years ago. So all the, all the dosing data and all the sort of preclinical work for the COVID is really with Ebola studies. And Gilead didn't move remdesivir forward for Ebola because when it was compared to other things like the other therapies for Ebola, it didn't do very well. So but that's also hard data to parse out because patients who have severe Ebola don't do well in general. So that drug was initially developed not for COVID but for Ebola but was found to have activity in Coronavirus including SARS, COVID-19 and MERS as well.

[Grant Burningham]
So we've seen a lot of hype around other drugs most recently hydroxychloroquine. The President even said, "what do we have to lose when we give this to patients?" Where are we with that drug right now?

[Kathy Yang]
Yeah, so I think hydroxychloroquine is sort of the best example of a drug where we really have to be cautious. And we have to really look at both in vitro data. So data that's in the lab versus patient data. So hydroxychloroquine, when really had pretty good in vitro data, meaning that it was active in, active against COVID-19 when you look at cell culture, so that's where it was getting all the hype and where everybody was excited, and in the absence of human data, we're going to always look at in vitro data, but as more and more people started using it, the data was not so good. Clearly, it was not very effective. And it has some serious toxicities associated with it. So the most important, of course, is the one about heart arrhythmias. So when President Trump is talking about what do you have to lose, what you can lose is the fact you could have a fatal arrhythmia. And if you know the safety, we have to really consider the safety on top of the efficacy. So in the in the setting where the safety is not so good, and it's not that efficacious, we really have to really think hard before giving that to patients.

[Grant Burningham]
So is there any hope with hydroxychloroquine in particular, are we still using that anywhere?

[Kathy Yang]
Yeah, so that's a really good question. Um, I think, as the hype for hydroxychloroquine has sort of leveled off, then the enthusiasm, for that drug has as well. So there are some centers that are still using it. We still have it on our formulary here, we still have it as an option. And it's being studied in multiple clinical trials across the country, including at UCSF for both inpatient and outpatient use for prophylaxis as well as in combination with azithromycin. So I don't think it's dead in the water I but I do think that we need to really look at the science and look at the clinical trials and not make rash decisions until we really know how it works.

[Grant Burningham]
So these two drugs hydroxychloroquine and remdesivir have been sort of the drugs that were getting all the spotlight right now. What else is out there, what scientists think might work and what are people trying?

[Kathy Yang]
Yeah, so Joe had mentioned in convalescent plasma, I think that's really exciting. And at UCSF we've used that I think between UCSF in and Zuckerberg we've had at least six or seven patients already. There might be more. And that's gonna at UCSF that can be obtained either through expanded access as well as a clinical trial that's going to be starting up soon. So I think convalescent plasma is exciting that's been used before for things like pandemic flu and 1918. So, there are some history associated with that. The other things that people are looking at are immune modulators that are often used for like rheumatoid arthritis, or lupus or psoriasis. These are drugs that sort of tamp down your own immune response. And they're important because as COVID infection in the long progresses, sort of, in the initial phase, it's really all about virus but towards the end, it's really about your own body's immune system, sort of becoming over inflamed and doing this thing called cytokine storm where you get an overreaction of your inflammatory cells that then damage your lungs. So these immune modulators are really important to see if they can tamp down that response and prevent the lung damage. So those are also a couple of drugs that are coming online at UCSF to be studied as well.

[Grant Burningham]
All right. Well, Kathy, thank you so much for taking time away from your very busy work right now, to talk to us. I'm going to move into a question and answer period here. We'll start off with one for Kathy. Kathy, this is from Nancy Sambol. "What was the patient population primarily level of severity of the NIH trial, one with the announced that the results announced yesterday?"

[Kathy Yang]
Yeah, so that one was mainly hospitalized patients. So they didn't, they could be intubated, but they didn't have to be intubated. So that was mainly just hospitalized patients only was pretty much the main thing and they had to have a specific oxygen requirement or in a chest X ray that looked like they had infection going on but it wasn't it, wasn't severe so they could be intubated but they didn't have to be.

[Grant Burningham]
Okay. We have some transportation questions, which I think are for Joe. Joe "has UCSF extended their policies for free parking and rideshare compensation to match the march 31 extension for shelter in place. The campus life service resource page lists a new rideshare discount program through Uber but this program along with the policies show on May 3 expiration date, this is in reference to employees who need to go into the lab to conduct COVID-19 research."

[Joe Guglielmo]
I do not have any answer to that question. Perhaps Michael Nordberg does, if not, especially if we can find out who it was that asset question we will. Well, that's an important question. We will answer it at the next town hall unless Michael has an answer to that question.

[Michael Nordberg]
No, I do not have the answer to that question. I have contacted transportation though with the two questions related to that, and we'll get back to Jeff Beck is one of the people I don't. Jimmy is the other person. I'm not sure what their last name is.

[Grant Burningham]
Okay, yeah. So, Jeff and Jimmy, we will get back to you on that. This is another this is a question from Nancy Hessel. "More broadly, if used more broadly, is there a sufficient supply of remdesivir?

[Kathy Yang]
I think that's a great question. So the CEO of Gilead said they were ramping up to make millions of doses by the end of the year. So I think that was their intent. The reason they moved from the compassionate use to the expanded access was to get drug into patients faster than having to do an individual request so that the drug more easily available and you can get it faster. There is also discussion of this emergency use authorization. I don't know if that will happen or not, but we should know that in the next couple of days.

[Grant Burningham]
Okay, a little lean on the questions today. So, Joe, if you want to take it over from here, I think we're done with the QA.

[Joe Guglielmo]
All right, thank you, Grant. Great job, Kathy, appreciate the really informative discussion is particularly on remdesivir. So I'm gonna remind you that we have another town hall scheduled. That will be next week, Thursday, May 7, it will be from three to 3:30pm, an Outlook invitation has already been sent. In addition, in closing, I want to make sure you all know: Please expect a very short survey via email after the town hall. We want to get a better idea of pressing topics of interest for many school colleagues, and I am assured that this survey is like 15 seconds, so please do that is that will inform us to make sure these town halls remain relevant and informative to all of you. In the meantime, once again, please stay safe and be well. Appreciate you participating. Bye.