Rethinking Rare Disease: Innovation and What's Next

The rare disease space is often overlooked, but it may be the most important laboratory we have for the future of medicine. Jimmy sits down with Rob Freishtat, board member of the Foundation for mRNA Medicines, to talk about what is actually driving collaboration between academic institutions and industry, what a changing regulatory landscape means for sites, and why financial viability and patient access are not as opposed as people think. Tune in now. 

Transcript

Jimmy Bechtel 0:00

Hello and welcome to SCRS Talks provided by the Society for Clinical Research Sites. My name's Jimmy Bechtel and I'm the Chief Site Success Officer with the Society. And with us today is Rob Freishtat. He is a board member with the foundation for MRNA Medicines, and he's here to share a little bit. With us about, some of this advancement in this area of medicine, and talk a little bit about, some assumptions and maybe some rumor and myth dispelling and how we continue to move, the science forward in that. But before we get into the topic today, Rob, I'd love to learn a little bit more about you and your background.

Rob Freishtat 0:38

Hey Jimmy. Thanks for having me on and, it's a real pleasure to be here. And, as, as we discussed, I'm a recovering physician scientist. I spent 25 years in academic medicine. in clinical medicine, as well as running a molecular genetics lab. After 25 years, in various roles, I left, to form a research site. I was one of the co-founders of Uncommon Cures, which is really set out to rethink the way we approach rare disease clinical trials in clinical trials in general, from a site perspective. and because my clinical domain, was emergency medicine, that means my attention span is super short. And so after about three years there, I was ready for new adventures and, left probably about six months ago to, embark on my own journey, and have been helping, lots of biotechs and pharma companies. Think through the process of clinical development and, and how they bring their science more quickly to patients. So happy to be here and excited for our talk.

Jimmy Bechtel 1:42

Yeah, I am as well. Excellent. And thank you for sharing that. And you know, Rob, it sounds like you sit at this crux of, integration and relationships, but we know. You know, collaboration, this buzzword in the industry between academic centers and industry rivals and, and regulators. It sounds great and we do our darnedest to try to bring examples of that forward, but it does tend to get kind of messy when it boils down to it in practice. So what. Has actually changed. That's making these partnerships work now when they really haven't before. When we look at, your perspective on the industry, but also the collaboration we saw behind the development of, these mRNA medicines.

Rob Freishtat 2:26

Yeah, so first a clarification. It's not kind of messy. It's really messy. and, the, siloing and bureaucracy has been a major impediment to progress. And what I've seen over the last year, really just in the last year is, A new openness to collaboration amongst entities that would never have collaborated in the past. And I tie a lot of that back to the baby KJ story. You know, the child with CCPs one deficiency, who was treated with the gene therapy at chop and. Successfully. So, and that process, although very complicated, very messy, and very expensive, showed that guess what? Academic institutions, industry, various thought leaders, regulators can actually work together and accomplish something. And because of that story and the inspiration and. Widespread publicity that it got. I think, at the end of the day, people are people and FOMO is real. You can no longer be the first, but you don't wanna be the last. So all of these institutions are. looking at opportunities to work together to do this kind of process in a sustainable way and are open to those discussions where they never were before. I mean, I'm working with several That honestly, When I started the process, would never have thought that, I mean, I didn't think they would work together. And they do. They, they are willing, they're open to new ideas and new ways to collaborate. Where they haven't before I'm excited by that. I'm excited that people are putting their, you know, not everybody, but a lot of people are putting their egos to the side and are like, how do we make this happen? We don't want to be left behind.

Jimmy Bechtel 4:19

it's a great point, Rob, because we have seen the power and the benefit now. That these collaborations can bring forth. it just took, a couple to kind of venture into the fold and, try to figure this out and make it work. And we've then used these as case studies for other organizations. And I hope that ball keeps rolling. And we're able to continue across the industry in various different capacities, to see that. And it really does start with an openness to, think a little bit outside of how we've done things. Traditionally, we're a very rigid industry, as you probably acutely understand. But when we do, we, we've seen benefit to that.

Rob Freishtat 4:59

Yeah. Well, I always say if it's not hard to do, it's probably not worth doing. As a general rule, and this is hard. This is absolutely hard, but it's also worth doing. and I think that's what's driving a lot of people to work through the problems that we face making this kind of thing happen.

Jimmy Bechtel 5:16

I want to lean into the regulator side of things as well too, Rob, in particular, because we know in recent years, the FDA has, invited those in the field to help shape the rules, and that's a shift in how things, traditionally works. So what does that process look like and how should sites start showing up to that conversation as a very important stakeholder in that equation?

Rob Freishtat 5:39

Yeah, so I mean the regulatory landscape, you know, I mean you read articles and people are concerned and rightly so. Unpredictability is very hard to plan around, Right. You be seeing the FDA swing back and forth on various things but maybe I'm generally an optimist, but I'm actually excited by it all because to your point, for the first time, the FDA is not saying Here's how to do it. They're saying Show us new ways to do it. Let's work together to find the best ways. And it's gonna be super messy. but I'm excited by it because it gives us the opportunity to go in there with. frankly, some out of the box ideas and say, Hey, here's what we wanna do. Can we work together to figure out a path to bring this to patients? it's very unusual for what. People who have been in this field for decades. It, it's certainly out of people's comfort zone but I see it as an opportunity. you know, we, we want to think outside the box. We wanna do things a new way. This is what we've been saying for the last 20 years. now's our chance and we have to accept that, there's gonna be stops and starts. It's gonna be unpredictable. In many cases. and what I always come back to is, before this change in tact, we complained about the FDA, how slow it was, how this was so process driven and not goal driven. and so what I say to people is, yeah, you can complain about it all you want, but it wasn't perfect before either. at least now we have an opportunity to have a say.

Jimmy Bechtel 7:10

And that's really what it boils down to for me, right? Is, is this, the door is open for a seat at the table. It's not, you know, overtly perverse in that, we can't affect everything, but it's these steps in the right direction that help us do some of this. And I think that was largely born. In part from necessity, as, as we've kind of been alluding to here, Rob, we don't, didn't really have a choice just given the direction that medicine and the industry, from clinical trials was headed. We needed to find a better way to work together and better ways to collaborate. And I, I'm encouraged. As it sounds that you are as well, that the FDA and, and potentially other regulatory oversight bodies have also, embarked upon this journey as well and let some of the industry in to, help guide some of what they, they dictate and how they go about approaching clinical trial execution and approvals.

Rob Freishtat 8:02

Totally, and I'll just comment that it's not just the FDA that is experimenting and, depending on what you're trying to do, there may be other countries, regulatory bodies that are particularly open to a path that is not tried and true. And I think as sites we need to be, as site sponsors everybody, we need to be looking at those opportunities What's the best venue to test these things out? the world is a big place. and there's lots of opportunity in the US and there's lots of opportunity X US

Jimmy Bechtel 8:31

That's right. And, everyone loves a little healthy competition, from amongst countries from trial to trial Well, Rob, there's been this assumption that financial viability rather, and patient access. Tend to be at odds with each other, right? The one suffers when the other one gains. And we can't seem to find an appropriate balance here, but what does it look like when an organization, I guess, rejects that trade off and builds what they're trying to do around both?

Rob Freishtat 8:58

Well, I, I mean, I don't see them as at odds with each other, right? First, I think you need to define what those things mean starting with patient access, in many ways patient access goes hands in hand with financial viability, right? The more patients that are using your drug, the more revenue you're generating from that drug, where it gets complicated is how much are you being reimbursed for a patient to have access and all of the XUS issues around different pricing models, different authorizations, et cetera. I don't think they're mutually exclusive I think they are tied together and you have to consider them together. At the end of the day, patient access is what's going to position you for success and for any sponsor for success. And especially in the rare space where there are limited numbers of patients. It's not like with You know, GLP-1 or a hypertension drug or something like that. It's not like there's a bottomless pit. you need to figure out how to. Give the patients who need your drug access, in a way that also helps you financially develop the next asset so, you know, I'm particularly tuned into the rare space and how important access is and frankly, how important the patients are to the development process. And so they deserve access on the backend. I think these are tied together, not, They're not exclusive ideas, they're not at odds. And you know, I would argue that this brings up a larger issue, which is, you know, traditionally pharma has been after that, you know, multi-billion dollar drug. And now most of the diseases are actually buckets of rare diseases. And as we get better at defining those subsets, we're gonna end up with different drugs for different subsets. And so patient access becomes a critical part of any financial viability model

Jimmy Bechtel 10:58

You make a lot of excellent points, Rob, and various lanes that we could go down and probably spend another couple hours talking about when we look at the challenges around patient access and the direction that we need to head and things like protocol complexity and this very niche I talk to people about it all the time. We complain about protocol complexity and it's like, well that's the nature of the diseases and how we are treating them has also gotten complex. So there is this baseline complexity that just continues to rise. but again, tying it back to making sure that we are acutely focused on, to your point both financial viability and patient access. Simultaneously without compromise is really the guiding light that we should be operating under and the path that we should be on as we continue to develop protocols and execute them at the sponsor and at the site side.

Rob Freishtat 11:51

There's no doubt, and like you said, there's multiple places we could take this conversation, but you know, the key thing is having the end goal in mind. Is the drug gonna be prepared for the patient. You know, a lot of cases I see a, a tablet formulation is what's being prepared all along. But the patients are all, G-tube fed or G-tube, you know, that's the only way they can swallow or the only way they can access the drug. And so the families have to add that extra step of grinding it up and then putting it in fluid so they can put it in the G tube. These are the kind of things that we need to be thinking about the whole clinical development pathway holistically, so that we make the decisions that improve access and financial viability.

Jimmy Bechtel 12:33

Excellent points, Rob. So I want to talk a little bit about ultra rare research and it's a space where we uncompromisingly have to focus on innovation by necessity. So what is the most important thing the broader industry should be pulling from this rare disease or ultra rare disease playbook as we move forward with other spaces where we're kind of implementing this concept of personalized medicine that we see in that rare space.

Rob Freishtat 13:02

So the ultra rare space is really interesting, with a lot of innovation and a lot of opportunity for further innovation. taken together the ultra rare diseases are actually quite common. and when you start looking at innovations that are happening, or are in process. like, you know, master protocols and process approval and ways to simplify some of the steps involved in bringing a drug to market, you know, these are diseases that traditionally have been ignored by pharma because, you know, you're talking about a handful of patients, you know, maybe up to a hundred, 500 patients. it's not a, it traditionally not been a financially viable. option and so it's been largely ignored but there are people out there who are moving commercial models forward in this space, new models. and that will be enabled by some of the innovations that we alluded to before around regulatory. So, it's a pretty exciting space because I think It's one where risk is more tolerated because there are no treatment options and patients are losing function and dying and they are demanding. That we move some of these assets forward, and they're very involved. Often they've developed the assets themselves with collaborators. And so, I think this is the space, this is the laboratory basically, that is going to, create the innovations around financials, around regulatory, around patient access, around clinical trials that are going to then bleed out into other more common diseases and common domains. And, so I think it's an exciting space to watch. It's an exciting space to participate in. it changes daily and there's just so much opportunity for new ideas and new technologies and new things to, to get the patients, the drugs that they deserve.

Jimmy Bechtel 14:58

Well, Rob, I think that's a really excellent place for us to end our conversation on that note of, forward looking positivity and optimism that we have in this space. And, I want to thank you for your time today and for your insights. I'm sure that our listeners gained something from that and, and a little bit of, where we're headed next as an industry as a whole. So again, thank you for your time today and, and thanks for being with us.

Rob Freishtat 15:21

Absolutely. My pleasure.

Jimmy Bechtel 15:23

And for those of you that are listening, thank you again for tuning in today. We look forward to continuing these discussions, highlighting other partners and innovations shaping our industry today. For more information on other site facing resources, visit our website, my scrs.org. Thanks again for listening, tuning in, and until next time.