Episode 309
Chasing Lifesaving Cures for Himself and Others - Dr. David Fajgenbaum, President of the Castleman Disease Collaborative Network
“I knew I wasn't going to survive unless I found a drug that could save my life,” says Dr. David Fajgenbaum, who has almost died five times from the rare disorder idiopathic multicentric Castleman disease, which he developed while in medical school. Now a physician and assistant professor at the University of Pennsylvania, Fajgenbaum has led research efforts into a cure for Castleman, discovering a drug that has kept him disease-free for eight years and is helping other patients. As he continues pursuing new therapies for Castleman, Fajgenbaum is also spearheading an effort to create a system for identifying alternate uses for existing drugs, something which could benefit millions in the rare disease community and beyond. “One of my favorite examples is tocilizumab, which was made for Castleman in the 1990’s and is now the first drug you'll receive if you're admitted to the ICU with COVID,” he tells host Shiv Gaglani. The non-profit effort is being announced this month at a Clinton Global Initiative meeting. Don’t miss this deeply inspiring conversation with many lessons on the importance of collaboration, laughter and hope, and the perspective gained from feeling like you are living on borrowed time. Mentioned in this episode: www.chasingmycure.com
Transcript
Shiv Gaglani: Hi, I'm Shiv Gaglani. The old saying, "Physician heal thyself," takes on a special meaning when considering our guest today, Dr. David Fajgenbaum. He's a specialist in immunology at the University of Pennsylvania with what you might call an intense sub-specialty in a rare disorder called Castleman disease, which he first developed while in medical school at Penn, and which has nearly killed him several times. His amazing story is captured in his memoir Chasing My Cure: A Doctor's Race to Turn Hope Into Action, which I read a couple months ago. It was tremendous, and I highly recommend to all of our learners too to check out his book.
Dr. Fajgenbaum is also co-founder and executive director of the Castleman Disease Collaborative Network, CDCN. I'm really looking forward to learning more about him and his work to find a cure for Castleman disease on today's show. So Dr. Fajgenbaum, thanks so much for taking the time to join us.
Dr. David Fajgenbaum: Thanks so much for having me.
Shiv: I feel like I already know you, even though this is the first time I've met you, just based on your wonderful memoir. But for our audiences' sake, who may not have read it yet, can you tell us a bit about your backstory? What got you interested in medicine and then particularly cancer and immunology?
Dr. Fajgenbaum: Sure, so, I'd always been interested in medicine but it wasn't until my mom was diagnosed with cancer while I was a freshman in college that I just decided to dedicate my life towards medicine. My mom was the most incredible person in the world and watching her battle with cancer made me want to dedicate my life to searching for treatments for patients like her. Unfortunately, she passed away about a year after her diagnosis. And like I said, that just drove me to want to go into medicine, to treat patients like her.
Then, fast forward a few years and I was a healthy third-year medical student. I was on this mission to hopefully treat patients like my mom one day, when out of nowhere I just became critically ill. I was literally from the perfect state of health to being hospitalized in the Intensive Care Unit with all of my organs shutting down.
As you mentioned, over the course of many months, I was eventually diagnosed with a horrible rare disease called Idiopathic Multicentric Castleman Disease. Unfortunately, I would go on to nearly die five times from this disease, even having my last rites read to me. But fortunately, with the diagnosis came treatment and for me that was chemotherapy, and so chemotherapy saved my life a number of times. But unfortunately, I would go on to have multiple relapses and I knew I wasn't going to survive unless I found a drug that could maybe save my life.
Shiv: It's incredible, how many ups and downs there were in your personal journey. You go through this in the memoir and how many roles you played. You were a medical student during this time. Before that, you were a quarterback at Georgetown. You were a super healthy person and wound up getting this condition out of nowhere. Then you also became a patient and you became a researcher. You got your MBA to run this foundation for this disease network.
Can you tell us a bit about what are some of the high points and low points that you want to share with our audience from your memoir just to paint the picture of how you wore all those different hats and wound up finding something that has restored your health?
Dr. Fajgenbaum: Yeah, there have been so many high points against the low points, as you're pointing out. I think that a real low point for me came when shortly before I received my diagnosis, I'd been in the hospital for about 11 weeks. I was so sick that my doctors told my family I wasn't going to survive. I remember there was a moment when I was in the hospital where I just wanted to give up. I had been in so much pain. With Castleman disease, your immune system attacks your vital organs until you die. It shuts down your liver, your kidneys, your bone marrow, your heart and your lungs in a relentless fashion until either you die or you treat it with some sort of treatment. I remember wanting to give up and thinking myself I've only got a few hours left to live and I'll be suffering and in pain. I should just give up, and of course here I am now over 12 years since that moment.
Of course, if I had given up, if I hadn't continued to fight for my survival, I would've thought that I was giving up on a few hours of pain and misery, but of course, I would have been giving up on hopefully, even more than 12 years of health. That's certainly a major low point.
I think in terms of the high points over the journey, there was...well, maybe I'll mention another low point before I get to the high point. That was that there was an experimental drug that was being studied for Castleman's and I was put on this drug and it was like so exciting, like, what are the chances that there's a rare disease drug being developed for Castleman disease and, oh my gosh, maybe it could help me and patients like me.
But unfortunately, I relapsed on that drug, the only drug in development. Of course, that was a major low point, because my doctor explained to me there were no more drugs in development, there were no more promising leads and if I was going to survive my only chance to survive would be to maybe find a drug myself or with a team of people that could save my life. I went on this journey to search for a drug and eventually found a drug that I've been on for now over eight and a half years and have been in a really good state of health. Definitely a high point was doing the scientific work that led to that discovery.
Maybe an even higher point was the next patient with Castleman disease we treated with the same drug and to watch her respond so well. In fact, the first three patients we treated with this drug really had a miraculous, incredible response. Unfortunately, we've subsequently found that it actually only works in about one third of patients, and so it's not the sort of uniform cure that we'd maybe hoped it would be, but it's been amazing to watch when this drug does save other patient's lives.
Shiv: Absolutely, and I remember you mentioning in the memoir about some of that where this diagnostic odyssey for some of these patients is so difficult. I mean the average rare disease patient takes what, four to nine years to get a diagnosis.
Dr. Fajgenbaum: Yeah.
Shiv: When there is a diagnosis, the chances of there being a drug that works for them is low. Which is why your story is so compelling in that you helped find that for yourself and for many other patients. I mentioned before we started this podcast, I was in medical school at Hopkins and you know that famous saying that you learn in med school, which is, "When you hear hoof beats, think horses, not zebras."
Dr. Fajgenbaum: Yes.
Shiv: But for 300 million people in the world, they have zebras. They have the one of 7,000 rare diseases, including things like Castleman. I'm curious, how has experiencing a rare disorder yourself and getting so involved in the rare disease community made you think about the way we train medical students, and other healthcare professionals? What are some things we could be doing better so that they spot the zebras or at least help patients who then have zebras?
Dr. Fajgenbaum: Well, first off, podcasts like this that you guys put on that raise awareness about the rare diseases...I think that's really important. One of the reasons why I wrote Chasing My Cure is to both raise awareness about all of these rare diseases, but maybe even more importantly around the fact that there are existing drugs that could potentially be repurposed to treat horrible diseases that already exist that are at your neighborhood pharmacy. I think awareness raising is one really big part of this. I do also think that we need to get from the world we're in right now -- which is where there are incredible tools to probe biology -- towards a world where we can use those tools to actually improve diagnosis and treatment.
For example, I'm talking about things like single cell RNA sequencing or serum proteomics that have gotten so good at understanding on a molecular level what's happening. But we have not yet fully advanced that to work to clinical use, where we can really leverage these incredible technologies to improve diagnosis and improve treatment.
One thing I'll mention...a couple of questions ago, you mentioned that after medical school I ended up doing an MBA and sort of how leadership fits into this whole journey. For me, I did the MBA because towards the end of medical school, when I was literally dying from this disease -- it had nearly killed me four times and it would nearly kill me one more time afterwards -- what I found as I got involved in the rare disease research space, was that the tools existed. There are incredible tools to understand what's happening in diseases, and there are ways to develop drugs.
The problem was bringing together the resources and getting people to actually work together. It is an organizational problem more so than a scientific problem. I think what I really challenge all of the listeners to do -- as you go on to become future leaders in healthcare, and as you are leaders in healthcare right now -- is to think about ways that we can harness and leverage the tools and the technologies that are already in hand. Whether that is something like serum proteomics to better diagnose patients with the rare diseases or it's to, as I mentioned earlier, to harness those drugs that are already sitting in your neighborhood pharmacy. We know that many diseases share many susceptibilities to the same drugs, the same genes and pathways are involved across a number of disorders.
If we can figure out ways to better understand what's happening in disease A and disease B and figure out that drug X is actually effective in both of them, we need to figure out ways to leverage those tools. The term for that is drug repurposing and it's about figuring out more purposes for every drug.
Shiv: Absolutely. That's one of the reasons we were excited to join Elsevier. They have this massive journal database of 2,500 plus journals...
Dr. Fajgenbaum: Yes,
Shiv: ...with hundreds of articles, if not thousands, on rare disorders. I know one of the most salient points from your memoir was how, when you were almost dying multiple times, you were reading these articles. You were finding the right doctors. You were connecting them and building up this network.
Dr. Fajgenbaum: Yeah.
Shiv: Some AI can help with that, if we figure out how to connect these people. I'd love to hear what are some tangible recommendations you think we should be doing, whether it's Elsevier, Osmosis, or it's health systems to kind of connect those dots?
My mentor Jan Herzhoff, who works here at Elsevier, that's one of his core themes: connecting the dots. That's exactly what you did, where the cure was out there or the therapy to prolong your life, which has had major impact on so many other rare disease patients, now, because of that. That was just connecting the dots.
Dr. Fajgenbaum: Exactly.
Shiv: So what are some examples of things we could be doing better?
Dr. Fajgenbaum: It's a great question. I think number one is that when you think about connecting the dots, you have to assume then that all the dots are there. I do believe that most of the dots are there, right? Organizations like Elsevier basically create the dots through all of these incredible journal articles and resources. But you're right, we have to connect them and so I think one thing that is critical in my opinion is to build a central unifying data source of all drugs and all diseases that those drugs already are known to have an effect on, and then the predictions on which ones they may be able to have an effect in as well as the diseases they're not effective in.
What we know right now is that there are a lot of publications proposing a lot of drugs - whether it's sirolimus for Castleman's or tocilizumab for COVID -- proposing this drug may be effective in this way. But there are a lot of dots and they're spread all over the place. What we need is a central resource to bring them all together, to connect those dots so that if you have a new diagnosis of Castleman disease and you fail to respond to the only drug in development, you can look to see, well, what's the next drug on this list that might be predicted to be effective? Maybe there's a whole body of literature around that drug and that disease, but it's just never been given to humans yet.
I'm not proposing that we get into this world where we're just testing things out of nowhere with no data to support it. But I am suggesting we get to a world where it's a bit more data-driven in terms of what do you do next? As someone who's been faced with this question of what do you do next when nothing that's known is effective, I can tell you that having all that information in one place would be tremendously valuable.
I can tell you that we're working on an initiative right now that we're going to announce at the Clinton Global Initiative, along with former President Clinton on September 19. It's a non-profit organization, fully-focused on centralizing data on drugs and diseases. It will focus on identifying the diseases where those drugs work, the diseases where they don't work and the diseases where there's strong evidence and support that they may work. That's not to say that you should take it if you have that disease, but it's to say, we need to garner the resource to do the clinical trial to prove that it actually works.
That way, you go from a disease that a drug may work in, to a disease where we know that drug works, or we know it doesn't work in. I strongly believe -- and it's something that President Clinton is strongly behind as well -- that humankind has developed nearly 3,000 different drugs, but I think all of us in medicine recognize that those 3,000 drugs have not been fully utilized for all the diseases they could be effective in.
As you know from my book, I believe myself to be on borrowed time. I consider myself in overtime where every second counts and you don't know how long overtime is going to last for. If I'm going to spend my overtime on the thing that I think is going to have the most impact, I believe very strongly that it's this opportunity to identify additional uses for existing drugs because these drugs are already in your neighborhood pharmacy and they could be delivered to patients the next day.
Shiv: That's incredibly compelling. We're excited about this announcement you guys are going to make, and we'll do our best to amplify it. We actually had Chelsea Clinton on our podcast as well.
Dr. Fajgenbaum: Really?
Shiv: So I wonder if she's involved at all with this with this initiative.
Dr. Fajgenbaum: I haven't gotten a chance to interact with her yet, but I actually will be seeing her at the event next month.
Shiv: Awesome, we'll see if we can connect those dots too. I'm glad to hear that they're involved in the rare disease space too. What advice would you give to medical students and other healthcare professionals about meeting the challenges of rare diseases and maybe their careers in general? You've had a pretty tremendous career already because of this personal diagnosis with Castleman disease. Say you were advising a medical student today, what advice would you have for them?
Dr. Fajgenbaum: I guess a couple things. The first is that my life really changed when I had my last rites read to me...when I realized that I was on overtime and I had limited time and needed to make the most of it. I kind of wish that I didn't need that to happen to me to live a life where I do the things that are most important and live a life where you're really intentional with how you spend your time.
One of the reasons I wrote Chasing My Cure is that I actually want to encourage other people to don't wait until you are on your death bed or until you've had your last rites read to you to make these sorts of decisions where it may be against the grain. It may not seem like the traditional path, but look at what you've done. Look at the impact you've had since making a nontraditional decision to leave an incredible place like Johns Hopkins after two years.
These decisions are hard to make and they feel scary, but if there is something in front of you that you're really excited about, you're passionate about, don't wait until you've had your last rites read to you to be compelled enough and confident enough to make those decisions. That's one thing, is that I'm in overtime, but actually we're all in overtime. None of us know how long our overtime is going to last for. When you find that thing that gets you excited, go for it.
The second is that I feel very confidently that, and strongly, that when you're in medical school and you hear the prevalence or the incidence of a particular rare disease, you may say, "Well, that's a small disease relative to let's say asthma or heart failure." But as you dig further, you realize that yes, each rare disease is small, but the opportunity to make an impact is often many times outsized compared to more common diseases because so little emphasis has been placed on rare diseases, and because there's often not a quarterback for that rare disease.
I really would encourage all medical students and healthcare professionals that have been intrigued by a rare disease but maybe have said, "Well, that's not where I'm going to spend my time because I've got limited time and I want to spend it on areas with the greatest impact," I really would encourage you to really reflect on what do you mean by impact? Do you mean by touching millions of lives in a way that may be imperceptible -- not to demean work for very common diseases -- but may be imperceptible on millions, or deep meaningful impact on say a thousand?
That's a hard question to answer and I think that it's important for all of us. First off, it's important for us to ask those questions. Then secondly, I think we really should reflect very hard on the potential that you can actually have, this incredible impact on people in a really deep way, if you focus on rare diseases.
Shiv: That's a common theme that comes up on these interviews. We had a gentleman named Philippe Pakter whose daughter has Pierre Robin sequence. He said the same thing...that for the hundreds of thousands or tens of thousands of people who have this condition, there is just eternal gratitude from the patient community for the physicians and the researchers who've dedicated their lives to that disease.
Dr. Fajgenbaum: It's incredible.
Shiv: Then the other thing is when drugs are repurposed or discovered for those conditions. The main example is familial hypercholesterolemia where the understanding of that disease led to the development of statins that then became a common therapy.
Dr. Fajgenbaum: Incredible.
Shiv: I'm sure you have other examples like that where rare disease research led to something that then impacted many people beyond that condition.
Dr. Fajgenbaum: Yeah, one of my favorites is tocilizumab. So tocilizumab, you'll remember from Chasing My Cure, was made for Castleman disease back in the nineties. Tocilizumab now is the first drug you'll receive if you're admitted to the ICU with COVID.
Shiv: Wow.
Dr. Fajgenbaum: It blocks interleukin-6 and it's saved tens of thousands of lives-- maybe it's close to hundreds of thousands by now -- of COVID patients. That was a Castleman's drug made 30 years ago. Yes, as you said, there are many others like that. I think there's just so many exciting opportunities in the rare disease space. When you think about what your career choice is going to be, it's both an opportunity to make an impact, but also reflecting on the plight of the patients that you're potentially going to help. In the rare disease space, we're unfortunately filled with people that are searching for solutions and need solutions. Like I said, the technologies are often there, it's a matter of just garnering the resources and doing the work.
Shiv: That's a great example. Now, if you were to write a follow-up to Chasing My Cure...a lot has happened to you. You've grown your family on the personal front. On the professional front, there's this exciting new initiative with the Clinton Global Initiative which you've alluded to. Obviously, you were instrumental in helping with the Penn Orphan Disease Center. Then Castleman...obviously doing a lot there. What are some of the highlights in the overtime, as you put it, that you'd like to fill our audience in on? What have you been up to the last few years since the memoir?
Dr. Fajgenbaum: I think that the easiest way to describe it is that Chasing My Cure, of course, is about my search for my cure. A drug that it's hard for me to believe, and sometimes it's just hard to even vocalize. For over eight and a half years, this drug has been helping me. But in that eight-and-a-half-year period, it's been about going from Chasing My Cure to chasing our cures.
Early on, it was about figuring out ways that this drug and others could help Castleman's patients. First, my drug was given to those Castleman's patients I mentioned. Then unfortunately we found out that the drug doesn't work for everyone, so we found other drugs for Castleman's patients, and we're still searching for more treatments. Because, unfortunately, there still are patients that we're not able to help and that pass away from this disease, despite our best efforts and so we're still very much pushing in the Castleman's realm.
But when COVID emerged, we began to think about how do we apply what we learned from chasing the Castleman's cure to chasing other disease cures. We built something called the Corona Project, which became the world's largest effort to identify, track and advance all the drugs being used for COVID. We took what drugs are being used, applied an algorithm to all of those drugs, determined which ones are As, which ones are Ds, which ones fall in the middle that we need more research into.
You'll remember throughout the pandemic that there were a number of drugs that were repeated over and over in the news. Some of those worked really well. Some of them didn't work so well, but there have actually have been over 600 drugs that have been given to COVID patients, many of which most people have never heard of. Some of them are actually really effective. Our idea, and really why we did, was to say, let's put this all in one place, let's grade things A through Ds, let's use the Bs as the ones that we do clinical trials of. Then we started doing this for COVID and it was making a big difference and it has made a difference. The NIH used our grades to pick drugs for the largest COVID trial, the trial called ACTIV-6.
Shiv: Wow.
Dr. Fajgenbaum: They picked the right drugs based on our data set and, I was like, "This is really cool." We synthesized all of this data, we picked drugs to go on this large trial. This is awesome for Castleman's and for COVID. But what about the other 12,000 -- or whatever the right number is -- diseases. That's what led us to this new initiative, which we're launching next month. Which is to say, let's pull together all this data into one place. Let's apply the same algorithm across all of the drug disease pairs to figure out which drug disease pairs look most promising.
But, let's do clinical trials to prove that they actually work. That that drug actually works in that disease it's predicted to work in. Let's change clinical practice from the world we're in right now -- which is where you kind of have to get lucky that the right doctor studying the right disease at the right time and does the right trial of the right drug...all these random things have to happen -- to let's get into a world where you don't need to have a Penn medical student or any medical student get a disease to figure out sirolimus can work for that disease.
Let's use algorithms in an unbiased way to figure out what's the next sirolimus for Castleman disease and let's study it. Let's do that in real time, so that if you or someone you love develops one of these horrible diseases, that we have a drug that's ready for you, whether or not that drug was initially intended for this disease. I think phase two, or this overtime, or I guess the sequel of the book would really be about chasing our cures and how do we apply what we did from Chasing My Cure to chasing many more cures.
Shiv: I love that. "Chasing Our Cures" I think will be the title of this episode as the follow up to Chasing My Cure. It's certainly something we'd love to follow up on because as I mentioned, Elsevier publishes 2,500 journals. I know there are great folks, including the CEO Kumsal, that have been helping forge collaborations with Orphan Net and the rare disease articles that they've published to see if we can put that data in there.
Another friend of mine, Arif Nathoo, started Komodo Health. They have a ton of data and are doing a lot of work with the CZI Rare As One Network and patient advocacy groups to get that data that's dispersed across all these health systems so that we can identify those patients who have these rare diseases and then connect that dot to the drugs, as you've just described.
I'm aware of your time. I feel like I could talk to you for hours longer about this stuff.
Dr. Fajgenbaum: I'd love it.
Shiv: But, for now, the last question I have is, is there anything else that you'd like to share with our audience about you, your journey, the rare disease space or healthcare in general before we let you go for the day?
Dr. Fajgenbaum: Sure. Maybe I'll close with a few lessons that stand out from this journey. I alluded a bit to a concept of hope and I think hope is really important during these really tough times. But I think hope is most powerful when hope inspires action. One exercise that I do is when I find myself hoping for something or wishing for something, I then ask, "Well, what can I do today to get closer to the thing that I'm hoping for?"
That's a practice that I do, and that I hope all of us will do. Because I think all of us are wishful hopeful people, right? We want cures, we want solutions. But I think as we find ourselves hoping and wishing and praying for things, we then say, "What can I do today, tomorrow and the next day to get closer to that." Again, that's something that's really changed my life.
Another that I'd highlight, and you'll know this from the book, is that I find humor to be really important during really tough times. It's not to make light of tough experiences, but it's really about laughing with the people you love. For me, it was a total game changer. Being in the ICU with my dad and my sisters and my now wife and finding something to laugh about with them helped me so much.
When you're in this horrible rare disease world where people are suffering and there's nothing funny at all, I think finding ways to connect with your patients, with their families, with one another around something that you can smile about together...at least for me, that's been like the ultimate therapy.
Shiv: I loved your example of Borat by the way, how you had a particular affinity for Borat and even had the...
Dr. Fajgenbaum: I did.
Shiv: ...Sacha Baron Cohen connection there.
Dr. Fajgenbaum: Yeah, no, I think Borat for me was like such an outlet. It was right after my mom passed away was the first time I ever heard or watched Borat the show. For me it was actually the first thing that made me laugh. I felt guilty laughing, or smiling, frankly, after my mom passed away. I was 19 years old and just...my soul was crushed. But all of a sudden -- it sounds so silly, verbalizing this -- but all of a sudden you meet this character Borat and he's just so ridiculous and so silly that I couldn't help but laugh. All of a sudden I was like, "Oh, this actually is a really good thing." It felt really good. All of a sudden, I'm the biggest Borat fan. I was Borat for I think six or seven Halloweens in a row.
You might say, "You're dressing up for Halloween still?" I guess I have to admit that every once...
Shiv: Stay young.
Dr. Fajgenbaum: ..in a while I still dress up and I'm trying to stay young.
Shiv: Overtime, yeah, I love it.
Dr. Fajgenbaum: Overtime, you got to laugh, right? Maybe the last thing I would say in terms of the lessons is around this concept of solutions hiding in plain sight. Sometimes we feel like discovering a new drug for a horrible disease is so overwhelming. "How could I make a difference?" I've certainly felt that way. But actually, a lot of times, there's solutions that are really within reach. We just have to figure out a new use for them. Of course, that goes for treatments. It goes for diagnostics. But I think that for anyone listening to this, you're already taking the first step towards your journey of making a difference in patient's lives by learning more about disease processes and patients and disease areas and ways that you can make a difference.
You're doing great work already. Keep up the good work for those patients like me that are hoping and praying for solutions. You all are the people who can turn that hope into action. You can actually do the work that leads to someone like me surviving. As a patient, I obviously want to say thank you to all the listeners for the work that you do. As a colleague, I want to say reach out if you're ever interested in getting involved in Castleman's research or drug repurposing work. You can follow all of our work by going to chasingmycure.com. You can join the newsletter list. You can find all of our social media handles and you can be on the lookout for this new drug repurposing initiative.
Shiv: I love that. Dr. Fajgenbaum, it's such a pleasure to connect with you. Your journey is so inspiring and there's so many lessons just in this short 25-minute podcast. My hope is everyone who listens to this goes and checks out your book and learns so much about being a physician, being a clinician, a researcher, and a patient. Truly inspiring.
Dr. Fajgenbaum: Oh, thanks so much. I so enjoyed this. I wish we could talk for much longer, but this has been awesome.
Shiv: Definitely. And with that, I'm Shiv Gaglani. Thank you to our audience for checking out today's show and remember to do your part to raise the line and strengthen our healthcare system. We're all in this together. Take care.