Lessons for biotech and pharma from a doctor who chased his own cure
After being struck by a rare disease as a healthy third year medical student, David Fajgenbaum began an arduous journey chasing his own cure. Amidst the hustle of this year’s JP Morgan conference, the digital trials platform Medable partnered with Endpoints Studio to share Dr. Fajgenbaum’s story with the drug development industry.
What follows is an edited transcript of the conversation between Medable CEO Dr. Michelle Longmire and Dr. Fajgenbaum, and it is full of lessons for biotech executives charged with bringing the next generation of medicines to patients.
Event hosted at Covo San Francisco. Photography by Jeff Rumans.
Hey guys, I’m David Fajgenbaum. It’s such an honor to be here with all of you, to share the stage with Michelle, and to be a part of what will hopefully be a great evening sharing my journey fighting Castleman disease. I’ll also share some lessons that you guys can take back to the work that you’re doing in biotech and pharma.
You see me sitting here before you and I look healthy and I feel healthy. And I guess technically I am healthy right now. But my journey has been long, and it’s been tough.
In July of 2010, I was training to become an oncologist in memory of my mom who had passed away just a few years before from cancer. I made a promise to her that I would dedicate my life to fighting cancer. I was halfway through medical school on that journey.
A few weeks later, I went from being totally healthy to experiencing multiple organ system failure.
My liver, my kidneys, my bone marrow, my heart and my lungs began to shut down. And over the course of just a few weeks, I was hospitalized. I was admitted to the intensive care unit. I had a retinal hemorrhage which made me blind in my left eye. I gained 70 pounds of fluid and drifted in and out of consciousness. I was on a feeding tube. I was getting blood transfusions daily.
I went from being this totally healthy medical student to having what I would write in medical records: MSOF. And I remember being in multi-system organ failure and thinking, when I was a medical student I just kind of so lackadaisically write MSOF and I had no idea what it really meant. When I was in MSOF it was a frightening time, and all with no diagnosis.
After 11 weeks I had a lymph node biopsy performed and that biopsy came back with a diagnosis of Castleman disease. Castleman’s is a rare immune system disorder where the immune system becomes hyper activated – it attacks and shuts down the body’s vital organs.
About 5,000 patients are diagnosed each year in the US with Castleman disease. So, it’s about as common as ALS. Most of you guys in here, probably everyone, has heard of ALS. I’m not going to ask you to raise your hands if you’d heard of Castleman disease before this. It’s a poorly understood disease. It’s also a disease with very little awareness.
But, with the diagnosis came hope. Two days before the diagnosis came in, I was so sick that my doctors didn’t think I would survive.
But I was diagnosed with Castleman’s, I was treated with chemotherapy. Finally, I got enough chemo – I got a combination of seven different chemotherapy agents – to where I was feeling well.
And you might say, well, chemo made you feel well? I was so sick, I actually felt better with every dose of chemotherapy.
Thanks to the chemotherapy, I was able to leave the hospital after months and months of hospitalization and start to really recover. I was able to go back to medical school and really hope that Castleman disease was in my rearview mirror. I was on an experimental drug called Cetuximab, the first drug to ever undergo a randomized controlled trial for Castleman disease. But unfortunately, I relapsed on that drug – the only drug in development.
I had a conversation with my doctor where he explained to me there were no more drugs in development. I asked him, “Well, what other targets are there? There must be cell types or signaling pathways, something else to go after.” And he said, “No, there are none.”
And that’s when I turned to my dad, my sisters and my girlfriend Katelyn, and I promised them, I said, “I’m going to dedicate the rest of my life, however long that may be, to trying to identify a treatment and maybe even a cure one day for this disease.”
And for me there were a couple of paths forward. The first was to begin to conduct laboratory research at the University of Pennsylvania where I was in medical school. The second was to create a foundation called the Castleman Disease Collaborative Network (CDCN), with the goal being to accelerate research on a global scale.
Through the CDCN, we’ve been able to make a lot of progress. We’ve raised and invested about a million dollars in research. Now it’s about $1.5 million in research over the last seven years. And from the 1.5 million we’ve put in, about $7 million in external funding has gone towards Castleman’s research. So really about a seven-extra turn on the amount of dollars that go towards Castleman’s research. And some really important breakthroughs, a new drug that’s undergoing clinical trials, diagnostic treatment guidelines. Lots of progress.
After I’d gotten engaged to get married, I had my fifth deadly flare of this disease and I spent another month in the hospital. Certainly, we did not think I would make it. But when I did survive, I really dove into my data. I went back into the lab and really dove into experiments to try to find something, maybe something that already existed, a drug that’s already FDA approved that could maybe help me.
And based on the experiments I did on my samples, I got a signal that suggested that the mTOR pathway, a critical pathway involved in T cell activation, VEGF production, cell proliferation, that it may be hyperactive in my samples.
And so, I decided to do a final experiment. This is a normal lymph node on the top of the screen. I wanted to confirm: Is mTOR really active in my samples? This is just a normal control. Blue stains positive for nuclei. So, it’s kind of just background standing. Brown is positive for mTOR activation, PSX. You can see there’s a little bit of brown in a normal lymph node. There’s some mTOR activation.
And then this is my lymph node and it was just striking the amount of brown mTOR activation in my lymph node tissue. And there’s a drug that targets the mTOR pathway called sirolimus. It was developed 30 years ago for kidney transplantation, had never been used in Castleman disease. And so, I started taking it. Today marks 70.27 months since my last relapse since starting that medication.
Today’s 70.27 months. And I say 70.27 because I know that I can’t round up. I don’t know if I will relapse tomorrow and if I will ever make it to 71 months. But I also refuse to round down because we worked really hard for the 0.27 months. I’m going to take every fraction that I can get.
I’m sure many of you guys are thinking about, well how is sirolimus helping other patients? I ended up finishing up medical school and then business school and starting a faculty position at Penn where I’ve dedicated my entire career in life to studying Castleman disease.
And what I found is the experiments that suggested sirolimas might work for me have also revealed increased mTOR signaling in other Castleman’s patients. And we’ve begun to give the drug off label.
The drugs have been given about to 20 patients with my disease. About eight of them, I think the exact number is eight, have responded. So, the drug does not work for everyone with Castleman disease, but it’s a meaningful response early on. We have a trial where we hope to enroll 24 patients in a formal clinical trial to understand how well this drug works, but we still are reminded there is work ahead.
Sometimes solutions can be hiding in plain sight. So, this drug that I’m on was developed 30 years ago for kidney transplantation. It had been sitting in my neighborhood pharmacy that I’d been walking past. During all those years when I was back and forth in and out of the hospital, it had always been there, but no one had thought to try it. How many drugs are there already out there that are just waiting to be found?
I’d love to hear about what it really takes to bring something like this in a world where we’re not always willing to
admit how little we know in trying to bring about something new to offer patients. And then there’s the public perception versus the reality of your condition in terms of what will they have to offer, where you really are today in medical research and new therapies.
Absolutely. Thank you for asking that question, Michelle. I think that it’s not something that we really want to talk about. I think that in medicine, doctors and medical students, we almost don’t like to talk about how little we know. These are stats that you guys probably all know, but there are 7,000 rare diseases out there with 95% not having a single FDA approved therapy. That’s shocking in this day and age. The first way you fix a problem is admitting you have a problem. Right? I think that there’s probably some value to us admitting that we have work to do.
And then, you made a great point about public perception. I think that we see headlines that talk about the breakthrough, but we don’t see a headline that says “100,000 experiments failed to produce a drug today”. But every day that’s what happens. And that’s not to discourage us. That’s not to say we shouldn’t keep trying. That’s to say we actually should keep trying and we should try even harder.
So, to answer your question as to how we fix this problem, I think that there are a couple themes from my experience that I think could be helpful. One is around collaboration and how – I didn’t talk too much about the CDCN – but really I think I’d say our secret ingredient to the progress that we’ve made is that we’ve leveraged the entire physician and research community to help to prioritize what research should be done. We call it crowdsourcing, but it’s just basically getting everyone’s input, prioritizing what should be done, and then going out and getting the best people to do it. It’s about getting everybody’s input. There are physicians who don’t have any research experience who are going to be able to propose great ideas because they are in the clinic with the patient; there are researchers who don’t have any clinical experience who can share things with physicians because they spend all day, every day working with those patients’ cell lines.
How do we really bring experts together to solve a hard problem? I think what’s so remarkable, you went out and you did that yourself. I’d love to hear about what you’ve learned through the Castleman Disease Collaborative Network and getting experts together and getting those insights together.
I’ve definitely learned that it’s not easy to do. We’ve gotten a lot of people to work together, but it has not been easy. And I’m getting 34 experts together to agree on, for instance, a diagnostic criteria, you could get 34 different diagnostic criteria from these 34 experts. And unfortunately, that’s just the way it is. And so, it’s not easy to get everyone to work together, but it’s so valuable when you’re able to.
Early on we had a hard time getting some of the biggest names in our field on board with what we were doing. Because what we were saying was that we wanted to get away from a world where the handful of experts in a particular rare disease have all of the power. They have all the samples, they have all the patients, they get all the grant money. We want a world where anyone and everyone who has a good idea can contribute that idea and then we find the best person to do the work, whether they’re a KOL or not. But right now, the KOLs are the ones with the samples. And you can’t do research if you don’t have those samples. And so, you can’t get those to the best researchers unless you figure out a way around this.
And so, we created a community where, like I said, it was very inclusive. Anyone and everyone can be a part of it. So many “non-KOLs”, like doctors who treat patients with Castleman disease, they got engaged, started producing really great ideas. We started publishing papers together.
Then all the KOLs started coming in and wanting to be a part of it. I think that it’s an important lesson. Within biopharma we like to go to the top of the mountain and get those key people. But there’s some lessons about getting – maybe they’re not the KOLs, but they’re the next tier. Get them involved. Then the KOLs would get involved.
And then another thing that’s really been essential is that before the KOLs got involved, because they had all the samples and the data, we would have been completely… our hands would have been completely tied to do research unless we figured out another way to get samples and data. And so, we created a natural history study where patients anywhere in the world can enroll online. So, no matter where you’re treated, whether it’s by a KOL or someone else, you can enroll online, and then we can get your medical records and extract the medical records into a database.
All of a sudden, all of these patients that were… I don’t want to make it seem too dramatic, but kind of held hostage by their treating physician, who had their samples and their data. Now those samples and data are freely available. And the same thing that we did with medical data, we also did that with samples. And so, I think just making it patient-centric is key.
Yeah. It seems like the more aware we are, the more we can drive more patient-driven decision making, or where we
can have more patient empowerment.
And one of the things that stands out about your study and about your story is, what if you hadn’t been a medical student?
What affected the decision? I’d love to hear how you think about a world where not every patient can also become a medical student.
I think that I mentioned earlier how challenging this whole journey has been, certainly emotionally challenging for my family and I. But also, just objectively, it was not an easy road for me at all. And I was a medical student at Penn. I’m the son of a doctor. I was in Philadelphia at this medical center, I had all the access you could possibly have. And it was a very tough journey. And there were many times where it very well just could have ended that day.
So, to your point, think about people who aren’t in the middle of medical school, who don’t have a family member in medicine, who aren’t in a big academic center hospital. That’s when you realize that we really have a lot of work to do.
What I hope is that experiences like mine, these kinds of N equals one, where you’re able to go from no treatment to a treatment, I think the most important thing is then taking that next step in the work that we’re trying to do, which is repeating the same experiments in other patients, understanding how this N equals one could become N equals many and expand that direction.
I think when we think about drug development we go from development for a disease, figure out who within the disease that drug works for and then personalize the therapy within that disease. And I think that our approach is kind of the opposite, where you start out by finding something that works in one person, then you figure out what portion of the population it works in. And that’s where it becomes a little bit more sustainable because it’s not sustainable to do this on a one off for everyone. It’s sustainable if you do this in one patient, and then you start asking the question: How many other people could this help?
Another really neat position you’re in is you must be one of the few in positions outside of hypertension and diabetes who lives with the condition you treat your patients for. And I’d just love to hear how you think about that and how living in this condition has shaped the care that you give to patients.
Yeah, I think you’re probably right. I’m sure everyone in this room has been touched by disease in some way, and that’s partly what drives you to do the work that you do. So, we all have something personal, but I think to your point, it’s a little different when you feel your port on your chest that you get chemo through.
But I think, for me, being on both sides of the fence has definitely made me better on both sides. As a patient, I think that I understand the limitations of a physician in the way that maybe I wouldn’t have understood otherwise. And all of us that are in medicine and work in biotech, we’re also all patients, right? If we’re not a patient yet, we’re going to be a patient at some point in the future. But all of us as patients, I think we have assumptions about the way the healthcare system works. Assumptions about how brilliant or not brilliant a doctor is, how good or bad he or she is. But I think that it’s made me realize kind of the human side. And I make mistakes all the time. So, I guess that means my doctors can make mistakes all the time. And I think that certainly has helped me.
From the medical side, I think that it’s given me an understanding of what it’s like to deal with illness in ways that maybe I wish I didn’t know, frankly. But I think that it is important because patients know their disease better than anyone else.
You’ve had some incredible breakthroughs around drug discovery. What do you see as the biggest barrier to having the most impact in your mission and your work?
I think that my story and the reason I’m here is really predicated on the fact that someone developed this drug, Sirolimus, years ago that had already gone through FDA approval, and on the experiments I was able to do using a new tool to understand biology.
To look in your rearview mirror at old drugs and say, well back when this drug was developed, these tools didn’t exist to be able to probe biology the way they do today. What I really think we need to do better – and I’m a huge proponent of this – is let’s use all these brand-new tools to better understand disease biology. And let’s ask questions about drugs that already exist. Drugs that were developed 20, 30, 40, 50 years ago, how can they help patients today?
I think the biggest barrier to that is frankly incentives and the fact that if that drug was already developed, and it’s already generic, you might be able to reformulate it but even if you do, then you could not prevent people from writing prescriptions for the old generic version. So there just are not financial incentives that exist.
And you guys in this room, and those people who are in other rooms that are part of JP Morgan, you guys are the people that can help think through solutions to that. You can be very creative around ways that you could actually incentivize repurposing existing drugs.
For me, in the work that I’m doing, we are so focused on patient impact that it doesn’t really matter if the drug’s generic and off patent and all of that, because we’re going to do trials. We’re going to get – whether it’s going to be privately funded or federally funded – we’re going to get money to do the trial so that we can see if this drug is going to save lives of Castleman’s patients. Every disease doesn’t necessarily have access to the capital to do that kind of stuff.
Trials are very expensive. Trials can be cheaper done in certain ways. But I think that figuring out how we incentivize repurposing is critical.
Definitely. What you’re basically saying is we need to know why a drug could exist and how it will work within the current reality. It’s about saying: Here’s a critical pathway of this disease, and here’s something that we think could work in that pathway.
One of the interesting comments that you had earlier when we were talking was that you receive an email a day from a physician somewhere in the world who has a patient with Castleman Disease and doesn’t know how to treat that patient. I would love to hear how you manage that with physicians who are in countries where they may not have access the drug, and how you loan them your expertise and provide that globally to people who treat patients.
I’m really excited that we’re working on a scalable solution. The solution as of right now is me writing manual emails to people who reach out to me. That’s not scalable. We used to have a platform on a website called GHD Online, and it was a place where physicians and researchers could post challenging cases. It was a place where anyone could post any ideas. The idea was that physicians in low resource countries could ask questions of physicians in high resource countries.
We were fortunate that that website, they gave us some space, and so we had a Castleman disease part of the website. And so, when people would send me a question, I would send them to GHD Online. They would post it to our community. The community would respond directly to that person. And the nice thing about that is that you’re educating the community along the way.
GHD Online actually shut down about a year ago. And so, we’re in the process of building our own kind of custom version of this. Actually, we’re partnering with the Chan Zuckerberg Initiative, so just down the street. CZI has supported us to build out this tool where physicians, patients and researchers – the patients will be separate from the physicians and researchers – but physicians, patients, researchers, will be able to post clinical cases that they’re dealing with and also research ideas. We’ll use this same place where we’re posting research questions and clinical questions to also identify and prioritize high-impact research studies.
I mean in medicine it shouldn’t just be one doctor emailing one doctor, and that’s it. It really should be made into a community where the whole community continuously learns from each case.
So, of the various things you’ve done – from discovering that Sirolimus could be used to treat Castleman Disease to creating a community to developing Castleman Disease Research Network – what is the thing that you could point to and say, I think this made the biggest difference?
I think thing that made the biggest difference was establishing a diagnostic criteria. It probably doesn’t seem that exciting, right, it’s not like new drugs or new technologies. But actually, if you don’t have a checklist to diagnose a disease, it’s really hard to diagnose that disease.
Before this diagnostic criteria, Castleman disease was first described by Benjamin Castleman back in 1954. And it’s been diagnosed in thousands of people over the last 70 years. However, for the first 65 years, there was no checklist. It was only diagnosed if you happened to come across a pathologist who knew what to look for, maybe they read a paper describing Castleman disease, or they read about it in a textbook, or they learned about it in residency. And that is just not the way things should be done. Right? Like you shouldn’t just have to randomly run into the right pathologist who sees the right lymph node at the right time.
So, we spent a lot of effort getting those experts together, going through data from over 200 patients to establish this diagnostic criteria. And so now patients actually get diagnosed based on a criteria.
As you look forward, what are you the most excited about for the new treatment of Castleman disease?
This is a rare disease, I mentioned that earlier, but we’ve been able to connect a really large community of Castleman disease patients. And we’re actually getting ready to launch a really big initiative to get blood samples from these patients so we can perform genetic sequencing on a number of patients and hope to really get to the underlying biology. What causes the immune system to just get out of control and start attacking vital organs? We don’t know. I’m really excited about this idea that we finally have the kind of the network in place to get dozens and even hundreds of samples to be able to do really important profiling. We’ve built the community. I’m now excited to start leveraging that network the samples and the data to be able to treat patients better.
I think outside of Castleman disease, I’m most optimistic about drug repurposing. I know I’ve said it a number of times, but the concept that for all these diseases out there that don’t have a solution, that maybe there’s a drug that could be helpful for them. That gives me a tremendous amount of hope.
Something that I think is remarkable is that when we look at the HIV crisis, AZT was also shown shelf drug. It was something that was on the shelf and was repurposed for the treatment of AIDS, and it was a game changer for that indication. What are things that we can do in the community to really drive our repurposing forward faster?
I think number one is trying to crack this code around incentivizing drug repurposing. How can you make it so that there truly is a financial incentive? I spent quite a bit of time a few years ago advocating for a bill called the Open Act that would make it so that drug companies that have a drug approved for a common disease, if they could get an approval for a rare disease, they’d get six extra months of market exclusivity. That would be a huge incentive, and we think that it also would lead to companies actually doing the effort to see if their drug would work in the rare disease space. It got really close. It was part of the 21st Century Cures Act. It was literally a day away from being signed before it got pulled out of legislation a couple of years ago, and it’s just been sitting on the Senate floor.
And of course, as you guys know in the current political climate, there’s no appetite for anything that could be even thought of as pro-pharma. And this is not pro-pharma. This is pro-patients. Yes, it’s an incentive for pharma, but unfortunately the political environment isn’t conducive.
Thalidomide is a great example of a drug that was developed for morning sickness, and obviously has a terrible history of causing birth defects, but now it’s this lifesaving drug in multiple myeloma. And so, remembering that there are these cases out there and thinking about how we improve the system so that we can leverage them.
Yeah. Actually, I’ve had patients that I’ve treated with lupus, who had severe lupus, alopecia, and extremely advanced disease. And Thalidomide was the only treatment.
I didn’t know that.
So how can we really better enable physicians to provide those insights around repurposing?
You’re hitting such an important point, and that’s tracking when things do get used. I think that, within disease states, capturing off-label drug use is critical because, to your point, even if there’s not a company behind Thalidomide in lupus, if doctors outside of Stanford that aren’t just the premier medical centers learn about this, they can get access to this drug, and it can continue to be used off-label.
And then I think it’s also important to figure out when drugs are being used off-label and there is a signal in the real world that it’s working. How can you do a clinical trial that is cheap enough and resource efficient enough to where you can actually efficiently and effectively and rigorously evaluate how well this works outside of the real world setting so that we’re not just relying on real world data?
I think that using the same technologies that help us understand disease biology across disease, we need to use those same technologies to understand biology within disease. So, cutting these diseases up based on, of course genomic, proteomics profiling, but also even based on response to this therapy or that therapy.
With Castleman disease, we’ve been able to subtype it a few different ways, proteomically and also histopathologically, but at the end of the day, what we really care is: Do you respond to first line therapy or not? Do you respond to second line therapy or not? Because that’s the only reason we do all this proteomics or anything, is about helping these patients. As a field we’ve been shifting towards getting away from calling it plasmacytic rich or calling it based on our proteomics subtype, but actually saying it’s siltuximab responder, siltuximab nonresponder, sirolimus responder, sirolimus nonresponder. Because that’s all we really care about at the end of the day, we want to get it to where there are no more non-responders, where there is a responder for everything.
Let me open it up to the audience.
My question is around innovation. We’re with JP Morgan, and really, your story is the epitome of breakthrough, or a series of breakthroughs, that led to maybe an advance. What advice do you have for folks around innovation?
That’s a great question. There’s kind of two thoughts with innovation. I think one is that innovation occurs when you’re really creative, and you’re not restricted.
And then there’s another school of thought: Innovation occurs when you’re really systematic. You start out with a lot of options, and then you start whittling them down, you test them out, you whittle it down, test it out, very much a systematic approach to innovation.
I’ve definitely taken this approach. I think that’s probably a personality thing, but I think that when you’re in a situation where there’s 1500 already FDA approved drugs, there are literally tens of thousands of different kinds of experiments you can do to try to figure out what drug could work for you. I think you have to apply some sort of systematic approach to trying to get from nothing to something. You can just too easily get lost. I mean, there literally are an infinite number of assays or partners that you could work with, so I think that my approach to innovation has always been: Let’s get everyone who has any idea at the table. They might have a bad idea, and that’s okay. If anyone has an idea, then we want to get it.
So, get as many good and bad ideas as you can, and then get a really, really dedicated group of people who are very smart to start sifting through those ideas, prioritizing them, and checking one another. Always relying on data, and then sifting down until you get to what you think is your best shot.
There’s 7000 cases of rare diseases. The majority of them are actually subtypes. Castleman’s is one of them, and it’sreferred to at the very end. The problem with having subtypes defined in terms of how they respond to treatment is dependent on having the treatments. Okay?
I don’t understand the biology of what these subtypes actually represent. I think, obviously, pragmatically, you want to associate both ends of that, and not just one end of that. And you really need to look at, in almost all these diseases, how the complex disorders have to be diagnosed and stratified because the first question would be: if the treatment that was successful for you actually fluctuated in other subtypes of Castleman’s, if they exist? So that’s one question.
The other side of it is you prefer to bring together a panel of experts to come up with diagnostic criteria. Well, I assume you probably use a Delphi method.
Okay, and the Delphi method is a consensus, and the problem with the consensus is you may range from 10 percent confidence to 90 percent confidence, so… It’s obviously a process that’s been used quite a bit. It’s a guideline. And then the next question is: what kind of clearance do you have from the physicians in actually defining those guidelines?
Good question. We use Delphi because, for the reasons you said, it’s been used before. I think Delphi works if you have good data to make your decisions based off of. We spent about two years getting together data from 288 patients, and so… you’re right, Delphi doesn’t work if it’s just opinions. It works, I think pretty well, if you’ve got a lot of data, and this is relative. In Castleman’s, 288 patients is a lot of data. And so, I think that helped us to always be focused on the data, and then building consensus around the data.
And the second question about how well people utilize it? I think better than you would think, mainly because most people diagnosing Castleman Disease are not people who are going to treat Castleman Disease. They’re ICU doctors. They’re internists who are working in the hospital. They’re PCPs. These are people who… They’re thrilled when they have a checklist to be able to say, “You know, I really think I’ve found a solution for my patient,” versus the hematologist oncologist who maybe will want to think, maybe it could be this even though the checklist says that. And then they don’t stick to it.
We work with a lot of diseases, have to deal with those consensuses. Even the NIH will tell you that in rare diseases, less than 30 percent are due to genetic causes, and so they’re much more complex than we would like them to be, but again because of the need to assign diagnostic criteria, or sometimes a DSM-5 code, we’re sort of restricted how we can describe them. I think challenges the ability to bring back old drugs because we’re looking at applying it to a heterogeneous population.
These are great points. See, I think that maybe you need to do both, and so you need to utilize all these brand new tools to profile them in every way possible, but then you need to also capture when drugs are used off-label to understand, to your point, how they connect. How does the profiling connect to the response to therapy? I wish there was an easy answer.
Have you thought about how to get interest from the venture community or pharma in actually investing dollars in research in pharmaceutical companies?
So, in our case, we have gone to partners that have been potentially good vendors and tried to establish partnerships, and sometimes it’s worked really well, where it really has aligned with business interests, but it doesn’t always align. We have had a great partnership with Janssen Pharmaceuticals to do this large serum proteomics profiling. They provided a bunch of samples. They were just terrific partners throughout the whole project, and I really don’t think it was based on a business case.
We were looking for pathways, other drugs that could be used in patients who don’t respond to siltuximab, so there’s almost clearly no business case whatsoever if you own siltuximab. But they made the case internally, because they were just a bunch of really great people who wanted to see progress for Castleman Disease. I think we should all look to create those kinds of partnerships, and we can really make progress.
Historically, if you think about how drugs even developed… Hundreds of patients enrolled in these sprawling clinical trials that could last 10 years that were extremely capital intensive, not particularly recourse efficient. So, I’m curious about what’s developed in recent years as a new model for drug adoption, especially in rare disease and ultra-rare disease. Even a one and two type ultra, ultra-rare disease where they might only have two or three known patients across the world.
I think that what I’ve been pleased to see what I would describe as the FDA’s being adaptive. I think that they’ve been adaptive in ways that, as a patient, have been positive.
For Siltuximab, the drug that’s approved for Castleman Disease, when the trial was done around 2009, 2010, it was incredibly stringent, the requirements that the FDA put in, and the bar to get that drug approved. The bar was incredibly high, and so I think that that’s been a good trend, is willingness to shift.
I think that from the biotech side of things, I’m just so thrilled to see there’s so much interest in rare disease. We call them orphan diseases. We’ve always called them orphan because they were rare and neglected. Fortunately, a lot of them are only now rare, they’re no longer neglected. So, let’s change the name back to rare. Let’s get rid of calling them orphan because maybe we can get to a point where they’re no longer neglected.
What can we really do in clinical drug development to change the game? I think we really need a world where we can connect patients to opportunities or give them better treatments directly, taking that opportunity and hope directly to patients. Screening and enrollment are the large component of time in a trial, so clinical drug development would be transformed if you knew, as a consumer, your opportunities for research. It’s such a simple thing, but when we rely on that point of care between a patient and physician, and physician is going to meet 30 other patients that day. I think we really need to remove that as a barrier and put that opportunity directly with patients.
I totally agree. I mean, I think what we have done with the registry direct online consent… We were talking about that earlier on. Going directly to the patient, being able to consent them online. IRB is being more flexible. I’m also a huge proponent of real-world evidence and figuring out ways that we can try to harness data that’s already being automatically generated. Obviously, it can’t replace clinical trial data, but I think that there are ways that it can supplement and support it.
Hope isn’t about casting a wish out into the universe, but it’s about taking action, it’s about making something materialize. So, you’ve made incredible progress with Castleman disease. How can everyone in this room be a part of that progress?
One is by helping to spread the word about what we’re doing with Castleman Disease. We call our approach to research we’ve spearheaded for Castleman’s the collaborative network approach. We hope that this approach can be used for many, many other rare diseases.
Obviously, you can donate towards the CDC. And the third is helping to raise awareness about the story, Chasing My Cure. What’s been so cool since the book came out a few months ago, we have more patients enrolling into our studies. There are patients getting diagnosed more quickly because their doctor saw something on the news about Chasing My Cure.
I learned so much about life and living from nearly dying five times. I got it on paper, and I want to get it out to the world, and so I hope you guys will help to share some of these messages as well, and help to spread the word about Chasing My Cure as well.
You can donate to the Castleman Disease Collaborative Network here.
Follow this link to David Fajgenbaum’s autobiographical book, Chasing My Cure.
For more information on Medable, click here.