Apr 15, 2021
Dr. David Fajgenbaum, physician-scientist and director of the Center for Cytokine Storm Treatment and Laboratory at the University of Pennsylvania, returns to the podcast to discuss the CORONA Project, a database of drugs being used to treat patients with COVID-19, and how these data are helping in the fight against the disease. Dr. Fajgenbaum is also the national bestselling author of Chasing My Cure, a memoir about his experience with Castleman disease, a rare condition that nearly killed him five times before he discovered a treatment that saved his life.
ASCO Daily News: Welcome to the ASCO Daily News Podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. My guest today is Dr. David Fajgenbaum, a physician and scientist who leads the Center for Cytokine Storm Treatment and Laboratory at the University of Pennsylvania. He joins me to discuss the CORONA Project, a database of off-label and new agents that are being used to treat patients with COVID-19, and how these data are helping in the fight against the disease.
Dr. Fajgenbaum is also the national bestselling author of Chasing My Cure, a memoir about his experience with Castleman Disease, a rare condition that nearly claimed his life five times before he discovered a treatment that saved his life. Dr. Fajgenbaum reports no conflicts of interest relating to our topic today. His full disclosures and those relating to all episodes of the podcast are available on our transcripts at asco.org/podcasts. Dr. Fajgenbaum, it's great to have you back on the podcast.
Dr. David Fajgenbaum: Thanks so much for having me back.
ASCO Daily News: So tell us about the CORONA Project and how it has helped in the fight against COVID-19.
Dr. David Fajgenbaum: Sure. So through the CORONA Project, our goal is to bring together all data available to identify the most promising treatments for COVID-19. Many of us have heard about the dozens, in fact, even hundreds of drugs that have been tried thus far to treat COVID. But, unfortunately, there was no central resource or repository for all that information, all that data to go, and so we've created that, and it's helping us to identify more and more promising treatments for this terrible pandemic.
ASCO Daily News: Can you tell us about specific advances? What drugs have specifically been identified as effective?
Dr. David Fajgenbaum: Sure. So we now know that over 400 different drugs have been tried to treat COVID patients worldwide, which is really just an astronomical number. And we also know that out of those over 400 drugs that have been tried, just a few of them have been definitively shown to be effective. So one of those is dexamethasone, an old and inexpensive immunosuppressant, that is most effective in the most severe cases of COVID.
And we also know that a drug called baricitinib, which also is an immunosuppressant, works in a specific window of patients with the most severe forms of COVID. Also, a drug called tocilizumab also seems to be effective in this really severe late stage. Unfortunately, there are fewer drugs as you move earlier into the disease course that have shown to be beneficial.
A drug called fluvoxamine, which is actually approved for obsessive compulsive disorder and is an antidepressant, showed a really promising result in an outpatient trial and now is being studied in larger numbers. So where we are now is that there are almost a handful that we know are effective if given at the right time of COVID. But we also know that there are at least a handful, maybe closer to 10, that look really promising, but they now need to be moved forward into a large scale randomized controlled trial.
ASCO Daily News: So the project has been useful in ruling out drugs that aren't effective, which is important as well.
Dr. David Fajgenbaum: That's right. And actually, there are a few that have made a lot of headlines. The drug hydroxychloroquine, in our data set we have found that it is the most prescribed drug according to our data set. We have over 270,000 patients worth of data in our data set, and over 80,000, almost one in three of those patients has received hydroxychloroquine. Despite its widespread use, there have now been 18 randomized controlled trials that have assessed whether hydroxychloroquine is effective at various stages of COVID.
And actually, out of those 18 trials, only one of them has shown an effect or a benefit, highlighting why it's so important to do these trials, and why it's so important to centralize the data in one place, so that we're not just kind of looking at things in a piecemeal fashion. It's about getting it all together in one place, so we can systematically even compare one drug to another.
ASCO Daily News: Absolutely. Well, is there any lesson or application from the CORONA Project in tracking and mobilizing against variants of the disease that threaten the effectiveness of some vaccines?
Dr. David Fajgenbaum: It's a really important question. We don't have any data on which drugs are more or less promising against certain variants. We both don't have data that would suggest that drugs that work against one variant will or will not work. But we also just don't have the data on when drugs are used for a particular patient with COVID, we basically never have data on which variant that patient had.
So this is a problem of missing data. The data doesn't exist. So our project is about bringing together all the data that do exist. That the challenge where the data just don't exist. Unfortunately, most of us, when we get tested for COVID, we don't know what variant we had and almost never is that variant ever connected to the treatments that we got and whether they worked or didn't.
I do suspect that as time goes on, I suspect more and more randomized controlled trials, and we'll at least do some testing for specific variants, so we can get a sense for whether some drugs work better against one than the other. But I would say that though there is some fairly solid data to support this idea that certain variants are more or less responsive to certain vaccines, there is not equivalent data to suggest that these variants would maybe make some drugs more or less effective. But of course, we're in pretty much a data-free zone.
ASCO Daily News: Right. Well, COVID-19 will never be eradicated unless it is stamped out everywhere. This means that working to get rid of it in the developing world is really important. What possible applications could the CORONA Project have here?
Dr. David Fajgenbaum: I think at the end of the day, no matter where you are in the world, no matter really anything else, it's all got to be about the data. We've got to lead with data. We've got to make decisions based on data. And there's a hierarchy of data, in the sense that you can sometimes hear about anecdotal reports of a drug in some cases, drugs like hydroxychloroquine, that looked really positive if you give them to a small number of people, and you don't have a comparator group.
But as you marched up the chain of rigor, towards these double-blind randomized controlled trials, where patients are either randomly given a drug or randomly not given that drug, then you can really get a sense for whether drugs actually work or don't work. And so I think regardless of whether you are in the United States or another country, I think we have to follow the data.
And it goes in the other direction too. So here in the United States, we need to pay attention to the data from all over the world. There are a number of really powerful and important trials that have come out of Brazil. There are trials all over the world that are being done, and so I think it's about forgetting about these geographic boundaries that exist between what we call countries.
When it comes to a pandemic, the virus doesn't care where you are or what country you may be from. And so I think it's about breaking down these walls and making sure that at all times, we follow the data that the drugs that look most promising are those that move forward to randomized controlled trials. And if they show benefit in a randomized controlled trial, that's when they get used in widespread use. And I think that it's about creating an infrastructure and a system so that happens efficiently, and that's what we're trying to do with the CORONA Project.
ASCO Daily News: Dr. Fajgenbaum, are there lessons learned in your endeavors that could be applied to put the principles of the CORONA Project to work on other conditions?
Dr. David Fajgenbaum: Absolutely. So as you know, one of the reasons that I was so motivated to want to go into studying repurposed drugs for COVID is that I'm alive today because of a repurposed drug for Castleman Disease. This idea of taking a drug approved for a completely different condition and trying it based on really strong data, in my case, in the lab. And so this idea of repurposing, I'm talking to you today, and I'm alive because of a repurposed drug, so I certainly believe strongly in this idea.
But I also recognize that repurposing can't be done without data. And so I'm very much inspired by the fact that I'm alive today because of repurposing and data behind repurposing. I feel really committed and compelled that we need to continue to build these sort of data structures so that we can identify the right drug for the right patient, regardless of what the drug was initially developed for.
These drugs, dexamethasone was not made for COVID. Tocilizumab was not made for COVID. Tocilizumab was actually made for Castleman Disease 30 years ago in Japan, and now here it is saving patients' lives from COVID, from rheumatoid arthritis, from heart CRS. And I think this concept of repurposing is such an untapped opportunity because unfortunately, there aren't really incentives to do it. So we've got to figure out ways to overcome the lack of incentives and find new uses for all drugs.
ASCO Daily News: Dr. Fajgenbaum, many people have been inspired by your bestselling memoir, Chasing My Cure: A Doctor's Race To Turn Hope Into Action. It was recently released in paperback. Congratulations on the success of the book. Are there any other big projects in the works?
Dr. David Fajgenbaum: Well, thank you so much. It's been so special to hear from readers about what it's meant to them. I learned so many lessons about life and hope and leadership from all of my ups and downs. And of course, I didn't, and I still don't, know how long this drug will work and how long I'll be fortunate to be here.
But it just is so special for me to know that this book and these lessons are reaching people far beyond me. And of course, this drug, as well, that I'm on is also reaching further than me. The new project that I'm focused on is really about thinking, how do we scale what we've done for Castleman's, both the drug that's saving my life, but also another drug that we've identified that we're repurposing for Castleman's.
And how can we go beyond what we've done for COVID to pull together data from all over the world, identify the most promising treatments, to think bigger than Castleman's and COVID and trying to get a sense for how can we solve this problem of drugs not being utilized for all of the different diseases that they could be effective for?
Cancer is a really great example of a field where there is a lot of repurposing done. There's a lot of really thoughtful data driven repurposing. One drug may have been developed for lung cancer, but we are going to use it for melanoma, and vise versa. This is done really well in cancer. But unfortunately, it's not done nearly as well outside of cancer. And I think if we can learn from the Castleman experience from the cancer experience, from the COVID experience and prove to ourselves that this can work, and it can save lives. We've got to figure out how to apply it to other diseases, as well.
ASCO Daily News: Well, I so appreciate you taking the time today to talk about the CORONA Project and the amazing work that you're doing. Is there anything else you'd like to add before we wrap up our discussion today?
Dr. David Fajgenbaum: I'd love for all listeners to check out the CORONA Project. We've made the project completely open source and freely available. If you go to cdcn.org/corona, you can access the data. You can play with the data.
You can see the 400 plus drugs that have been tried. You can see the rating scale that we've assigned to each of the drugs to get a sense for what the drug was the most promising and least promising. So I really encourage you to go to that website. In addition to following our work, you can also get involved in our work. We actually have a number of positions open where we're looking for immunologists. We're looking for data scientists, data coordinators, individuals who want to be a part of identifying treatments as quickly as possible for COVID-19 and looking beyond COVID.
So you can go also to cdcn.org/corona to understand about and to learn about some of our job opportunities. And we'd just be thrilled for anyone to reach out that's interested.
I also encourage you to go to chasingmycure.com. You can follow the work that we're doing. You can learn more about the lessons that I'm trying so hard to share from my journey, and also related to drug repurposing and certainly follow us in real time by finding out all the different social media handles.
And I would love to engage anyone and everyone listening that is excited about drug repurposing, whether it's for COVID or cancer or any other condition. I would love for you to reach out, and you can find my information at chasingmycure.com.
ASCO Daily News: Fantastic. Thank you so much, Dr. Fajgenbaum, for talking to us today on the ASCO Daily News podcast.
Dr. David Fajgenbaum: Thanks so much for having me.
ASCO Daily News: And thank you to our listeners for your time today. If you're enjoying the content on the podcast, please take a moment to rate and review us wherever you get your podcasts.
Disclosures: Dr. David Fajgenbaum
Honoraria: Foundation Medicine
Consulting or Advisory Role: SOBI
Research Funding: EUSA Pharma, Janssen
Patents, Royalties, Other Intellectual Property: Provisional patent pending
Travel, Accommodations, Expenses: EUSA Pharma
Other Relationship: Pfizer
The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.