Why 80% of Life-Saving Drugs Are Being Ignored by the Medical System | Dr. David Fajgenbaum | Be Well Moments

0:00Dr. David Fajgenbaum:Welcome to Live Well, Be Well, a show to help high performers improve their health and well-being.

0:10Your work now focuses on drug repurposing. That's right. Right. So you said something yesterday where there's 400 diseases.

0:16Dr. David Fajgenbaum:4 ,000. 4 ,000? No. Sorry, 4 ,000 improved drugs. Yeah. Sorry, yes. And 400. So is it 400 or 4 ,000 diseases and the exact same number of drugs to match, right? It's 4 ,000, 4 ,000, yep. Okay. And how many diseases are there, autoimmune diseases, that kind of don't have these drugs matched? There's a lot of autoimmune diseases that don't have a treatment for them. There's approved. And exactly, yesterday we were talking about how there may not be an approved drug for your autoimmune disease, but there might be an approved drug for another autoimmune disease or maybe an approved drug for a cancer or for transplant rejection, and all of them work on the immune system.

0:55Dr. David Fajgenbaum:And so they might actually work for your autoimmune disease. And so that's, yeah, that's where my, all I can think about is how do we use those 4 ,000 approved drugs that we have that are currently approved for 4 ,000 diseases, but how do we use them for the diseases that don't have any treatments like these autoimmune diseases you mentioned? What got you onto this train of thinking? Because obviously you said, I don't have a million dollars. A billion, yeah. A billion dollars and all of this kind of research into how we repurpose a brand new drug for this disease. so how did your mindset go from okay i'm going to go into drug repurposing and have the confidence to to start going down that route like what was that initial yeah i mean for me it was really just it was the realization that was my own my only route to finding a drug that could save me would be to repurpose an existing medicine you know i didn't have the resources i didn't have the time to create a new drug and i wouldn't have anyway i mean i just that's it's so hard and challenging but to me it became so simple i was like what if that you know other drug over there that could work for me And the reason, the real driver for that was that those chemotherapies I was getting, they weren't made for Castleman disease.

1:57Dr. David Fajgenbaum:They were made for other diseases. So my doctors, they're telling me, well, there's nothing left for Castleman's. Like, well, you tried those seven chemotherapies and they didn't work long term. I kept relapsing. So they weren't like the cure. But if they could work short term, maybe there's another drug for another disease that could also work short term or long term. And so this idea that like, you know, when a doctor tells you like, we've tried everything, there's nothing else that we can do. yes, we've tried everything that the medical system knows about, but like that doesn't mean that we've tried everything.

2:24Dr. David Fajgenbaum:And so that for me, and then when, of course, when I discovered this drug that could save me, sirolimus and months started passing by and it wasn't until we were like 38 months before I started saying, counting in years. Right. Cause it was like, I just didn't know how long this remission would last. It was like, you know, counting by the month and every month, just, you know, afraid if I would relapse, but the months have added up now it's 11 years. But as the time went by, it just became so clear to me that, oh my gosh, I've just stumbled upon this incredible realization. And that's that we can save a lot of lives today and tomorrow with the things that we already have.

3:01Dr. David Fajgenbaum:We're so forward-looking. What's the next drug? And I think that the other thing that really resonated or was so clear to me was that a lot of this has to do with financial incentives. And that's that all drugs become generic within 8 to 12 years of becoming approved. And once a drug is generic, you can make tons and tons of different versions of it or different companies can make copies of it. And so no one makes any profit once it's generic. And so that means that 80 % of our drugs that we have, they're all generic. So no one makes any profit off of it. So even if you found a life-saving use for one of these old 80 % of drugs that could treat millions of people, literally no one in our whole system is incentivized to do anything about it.

3:37Dr. David Fajgenbaum:And so what that means is there's all these opportunities out there to use these old, safe, inexpensive drugs in new ways, but no one with any motivation to do the work. 11 years on, do you have an understanding of how this drug has saved your life? I do, yeah. So this drug, it's approved for organ transplant rejection. And the way that it does that is so like if you were to get a kidney transplant, your immune system would notice that it's a kidney from someone else. And it would start to try to sense and understand like what is this foreign object. and it would turn on something called the mTOR communication line.

4:09Dr. David Fajgenbaum:And mTOR is a way that immune cells communicate with one another and basically say, like, this is bad. Like, I just found something. I don't know what it is. It might be a kidney, but I don't know. But it's something bad. And then now all these immune cells, they start telling one another, like, hit the mTOR switch. And that tells them to start proliferating, to start multiplying, and to start getting into an attack mode. Well, serolimus, the drug I'm on, works by turning off mTOR. And so even if you were to get that kidney, and now your immune cells go and they're looking at this kidney to try to figure out, you know, what is this thing?

4:38Dr. David Fajgenbaum:If you're on an mTOR inhibitor and it goes to turn on its mTOR switch to say, let's fight this thing, it can't. And so that way you can have a healthy kidney that got transplanted in you and you don't attack it. Well, it does the same thing in my body. Because the reason I decided to try serolimus is because I discovered that that communication line mTOR was turned into overdrive in my immune system. And I didn't get a transplant. Like there was no, I don't have two normal kidneys for me. There was no organ in me for them to reject, but the immune system was on as though there was something to fight.

5:09Dr. David Fajgenbaum:And by turning off mTOR, that's gotten my immune system back into this sort of like surveillance mode. And it means that my immune system is weak. And so I can, you know, get very bad infections very quickly. And I have to worry about that sort of stuff. But I've been very fortunate. I'm going to knock on some wood. Yeah, well done. I'm going to knock on wood for you. Thank you. I think it's completely fascinating that, you know, you're now on this journey. There was somebody in the audience yesterday to post this. You've gone to set up two not-for-profits. It's incredible to have a doctor here who has saved his own life, his self, by looking at a new way of drug treatment and repurposing and not having to try a new drug each time.

5:50But now your mission to do this for so many other people who feel unhopeful.

5:55Dr. David Fajgenbaum:Yeah. Yeah. And for me, it was, wow, okay, it worked for me. Maybe we got lucky. And then I joined the faculty at University of Pennsylvania and we kept doing this kind of research. And then we discovered a treatment that could be repurposed for poem syndrome and one for angiosarcoma and another one for one form of Castleman's and another form of Castleman's. And all of a sudden, like, we're like, maybe we're not just getting lucky. Maybe there's a lot of things out there. and the contrast of it is that we've got people who are alive today because of drugs we repurpose for them if we hadn't repurposed it for them they wouldn't be alive and then but then i also start thinking well what about all the people before them you know for the last 10 15 20 years since that drug came out for this one disease all these people suffered and died when there was a drug that was at their pharmacy just no one knew that it could work on their disease and so it creates this for me, this is tremendous sense of responsibility and purpose and sense of urgency that like, there's drugs out there that could help people.

6:52Dr. David Fajgenbaum:And there's people who are suffering and there's no one doing the matching and like someone has to do it. And, and if I'm going to, you know, be alive because of repurposed drug, I sort of feel like I owe the universe. Like I should be doing the matching, right? Cause I've come across this thing. That's like literally, you know, we've saved thousands of lives with drugs that weren't made for these people's diseases and they would just be dead if we hadn't repurposed the drugs for them. So it's like, oh my gosh, how many more are out there? And so that's why almost three years ago, we set up a nonprofit called Every Cure, which is on this just huge mission, a very audacious mission, to unlock the full potential of every approved drug to treat every disease that it possibly can so that we don't just have, you know, one drug is approved for one or two diseases, but let's find all the diseases that can benefit.

7:37Dr. David Fajgenbaum:And we are just all in on it. How are you using AI in this whole system? because this has been the biggest topic of today. And what I've, I mean, we've just listened to Sam Alderman speak, right? So open AI. And there's been a mixed bag. This is the thing that Ted brings, right? Controversy brings two camps. Yours feels very hopeful with AI. Tell me about how you're using AI during this whole integration period of drug repurposing. Sure. So we use AI to scan across everything the world knows about every drug and every disease. and then to look for the points of connection between drugs and diseases.

8:14Dr. David Fajgenbaum:So I shared about how Viagra is very famous for having gone from being a treatment for heart disease to its well-known use. But interestingly, it also treats a rare pediatric lung disease because these kids were dying because they weren't getting enough blood flow to their lungs. Well, Viagra is very good at increasing blood flow. And so it can increase blood flow to the lungs of these kids, and they live full lives on Viagra. And so what AI can do is the point of connection there between pulmonary hypertension, which is that pediatric illness and erectile dysfunction and heart disease is increasing blood flow.

8:49Dr. David Fajgenbaum:And so what artificial intelligence can do is it can look for those points of connection between drugs and diseases. What's a similarity between two diseases or maybe a similarity between two drugs? And can we make can we find a mutual connection between them? And this is the kind of stuff that humans can do. We can make those connections. I mean, the sirolimus example, what I did for myself, that was like, okay, I found too high of mTOR in my immune cells. What other diseases have too high of mTOR? Okay, organ transplantation. What drug treats organ transplantation? Okay, sirolimus does. Well, then maybe sirolimus can treat Castleman disease.

9:17Dr. David Fajgenbaum:So us humans, we can do that. The reason we really need AI is that there are 4 ,000 drugs, and in total, there are 18 ,000 diseases. And so if you tried every drug and every disease, it would be 75 million tries. and so like us humans can't actually look across 75 million connections and be like oh that looks good or that doesn't look as good and so what we use ai for is to actually give us a score for all 75 million calculations so if you tried every drug for every disease and then us humans can look at the things at the top like what are the things that are scoring 0.99 wow this looks really promising let's look into it further and then so that's what our non-profit does is that once with the things that score really highly by our ai algorithm we get really smart humans to look at them and say wow, should we do some more laboratory work?

10:00Dr. David Fajgenbaum:Should we do clinical trials? Or should we just go right to raising awareness because this looks so promising? Thanks so much for listening. To hear the full episode, there's a link in the description.