Rare Disease Day Special: The stats and stories you need to hear.

Welcome to let's Talk Rare, a monthly podcast from Partners for Access where we discuss news, views and the latest insights from the orphan drug and cell and gene therapy world. Hello and welcome to the P4A podcast, let's talk Rare. I'm your host, Owen Bryant, and joined as ever by my wonderful co host, Georgie Rack. How you doing, Georgie? Hi, Owen. Good, thanks. You? Yeah, wonderful, thank you. It's a special episode because today we're marking Rare Disease Day. I'm delighted to be joined also by IRO Malaku. Iro, how are you doing? I'm doing great. Great to be back. Owen, how are you? Yeah, very well, thank you. Very well. It's always lovely to have you on let's Talk Rare. And it's going to be a great episode. Really looking forward to it. Before we start, I just want to make one little special announcement. The wonderful Georgina ak, co host of let's Talk Rare and the most wonder, one of the most wonderful people I've ever worked with. I can't say the most wonderful because my wife might be listening, but one of the most wonderful people I've ever worked is getting married. Georgie, what's going on? I know, can you believe it? I'm no longer going to be a wreck and I'm now going to be an Underwood. So, yeah, getting married. Well, I'll be married before this podcast episode is, is out live, guys. So yeah, it's, it's exciting but a little bit scary at the same time. So don't worry if you see Georgie Underwood on the next one, it's not a different person. It's just the same person, but with a different name. So we wish you all the most wonderful happiness, joy and hope. You have a wonderful day and the best of luck. We'll have our fingers crossed for you and I'm sure all our listeners will too. Thank you so much. Thank you. Okay, let's get into it at Partners for Access. Rare diseases are really at the heart of what we do. From our work supporting orphan drug launches to our sessions that we've hosted at the the World Orphan Drug Congress and lots of other conferences that we, we've taken part in over the years on the EU joint HTA and gene therapies. Obviously our new Pico plus digital tool, which is just amazing, guys, if you haven't seen it, I do recommend you, you sign up and get a demo of that tool. It's just, it's amazing, it's brilliant. But today I think really we want to step back and ask two simple Questions, how big is the rare disease challenge? And how do we make sure that the patient voices are shaping HTA decisions that affect their lives? And I think that that's a really, really important. You know, we've spoken about the patient voice. I mean, personally, for me, I've been doing the podcast five years now, and my very, very first podcast episode was a rare disease special, and we asked the same questions. And five years later, we're still asking the same questions, and we're still talking about the patient input and the patient voice in HTA decisions, and it's still ever more important. And let's have a look. Let's look at some numbers, see if there's any changes from when we recorded, you know, kind of five years ago to where we're landing now. And that's the thing with these questions is, you know, you ask one question, then five years later, you're asking the same question. It means it's a big question. It means it's a question that on the surface sounds simple, but actually, the more you dive into, it becomes more and more complex. And I think one of the best ways is to start with the numbers. Let's unpack a little bit about the scale of rare disease. They're often thought of as rare, but together they represent one of the largest patient populations in healthcare. Let's dive into some facts here. By the latest counting, There are over 7,000 rare diseases identified worldwide. But, and that's the thing with a lot of these statistics, it's quite hard to absolutely pigeonhole these numbers. So sometimes you hear 7,000, sometimes you hear up to 8,000. There is sort of a discrepancy, but we're looking to between 7 and 8,000, which is a lot of rare disease. It really is. And when you're looking at Even that, over 300 million people globally are living with the rare disease. I mean, that's a huge statistic, isn't it? That is massive. I mean, again, and people even said that could be up to 400 million. So we're looking at the size of the population of the United States, which is one of the most densely populated countries in the world. That is a huge amount of people. So it's not that rare, really. When you look at it in those. In the. In that perspective. Yeah. And then you just look at Europe alone, though. That's 30 million people in Europe. And when you think of that in the context of how many people is that? That's roughly the population of Poland. It's right. I mean, it's incredible when you're looking at those stats. And I'm really thinking of the families that are living and having to go through these, these some devastating diseases. I mean, that's. So there's a lot of people we've, we've identified that actually rare. Isn't that rare. And there's a huge amount of people across the world who are affected, not just themselves of rare disease, but obviously their support networks too. Now let's actually look into the makeup of these rare diseases and what they actually are.72%, which is the most accurate reading we've got of rare diseases, are genetic. And 70% of them begin in childhood. Yeah. So it's not just. It affects a lot of people, it's affecting predominantly children, which as we all know, are innocents. And when disease affects innocence, it's just absolutely awful. Well, Aero, what do you think of those stats? We just unpacked. I mean, we talk about these things around these things a lot. But any of those stats surprise you? It's really a very significant proportion of the population. And when we're thinking about genetically driven rare diseases that begin in childhood, they're often very devastating diseases. And I'm sure we'll also talk about the treatments that are available, which are currently limited. Absolutely. We've laid out that it's not a rare problem and actually is affecting children. And, you know, most societies want to do absolutely everything they can to protect children. It's one of the things that's built into us as humans. Yet despite all of this, only about 5 to 10% of rare diseases have an approved treatment, which I think is mad. It's crazy when, when you hear that, isn't it? It's. It's quite scary when you, when you read those statistics, actually, and then you even think, you know, that that's if you can get the treatment, because the diagnosis takes an average. And I imagine because maybe some GPs physicians, they've never heard of these diseases, they just have no idea what they are. And a lot of it in childhood. I think in certain illnesses, you know, they're typical things that toddlers would do. You know, maybe they're a little bit more clumsier or they're falling over a little bit more, or, you know, they start hitting milestones and then start regressing back. And it's really hard for parents because they know their children and they get this gut instinct and they know something's not right. And you go to see your GPs or your physicians, you go to see your healthcare providers and you know, they just think you're an over the top mum, or they just think, you know, there's no and. And they're not really hearing and listening because they're such minor symptoms that, that start off that can really easily be tied into just normal toddler or, you know, behaviors that babies do. So again, it's very, very difficult. So I think, you know, it's awareness, it's awareness of these rare diseases. It's really trying to highlight what the, what these diseases cause, what symptoms to look out for and actually who to refer you on to. What is the right specialist to send these people to to actually make sure you're getting that diagnosis quickly. Because I think the biggest thing in rare disease and especially gene therapies are the faster you get that treatment, the better your outcomes are going to be. So, you know, it's a real, it's a real tricky one for, for anyone out there with the rare disease or the families that are, you know, suffering also with them. It's hard, isn't it, Hero? Because we, we, we often panic about things that we, we don't understand. And you go to your GP and something's the matter and they say, what is this? And you go away. It just doesn't solve the problem and it must. I mean, we've all probably been there, but can you imagine the panic if it's your child that that's happening to? It must just be awful. Yeah. And that's why they call it the diagnostic Odyssey. It just takes a huge toll on the patients and on their families as well. Yeah, I think apparently, you know, we're looking at. Patients often go up to six to eight specialists before they receive the right diagnosis. And like you said, that is an odyssey. That is a journey. That is, that is every time you go, that's a journey to see a specialist that's worried about it, that's then unpacking what they've told you afterwards and then that's all the unraveling of that information. Then you go through it again and again and again. And these are the things that unless you talk about, you just kind of take for granted and the things that rare disease patients have to go through all the time. So that's one of the great things about Rare Disease Day. It actually puts the patient first and foremost. You know, it's not just an illness, it's a person behind that illness. And that's what we want to sort of get into today. And actually the power of that person and what they can help evolve in Healthcare. So look, these aren't just stats, they represent years of uncertainty, don't they? We've gone on to that. But here's another important reality. Rare disease patients are not evenly distributed. Each condition may affect only a few thousand or a few hundred worldwide. And that obviously has impacts for treatment. And what are those impacts, Georgie? Well, clinical trials, it's really difficult to find the patients for a clinical trial. And if you say that there's only a few hundred worldwide. Yeah, it's very, very difficult to get the real good data that you need from these really small clinical trials. And also finding, as I said, the right patients, the evidence is really limited. And also the HTA decisions around that then become incredibly complex. Even just unpacking those three things, we could have podcasts and all three of those things. We've spoken to some really clever people over the last couple of years. Things that they're helping with AI, helping to understand more about clinical trials and to marry people and how evidence is being generated in different forms and fashions now, nowadays. And also hga, the strides that have been made in that recently, which we'll get into, it's always one of these things, I think. Why is HGA so different from for rare diseases here? What's going on there? Given some ideas, but why is it so different? I would say back to the point that you mentioned, Georgie, that evidence is limited. And when we really think about what that means, if you're developing a treatment in a space where there isn't one already, you don't have established endpoints, you don't have anything to compare it to. So it's really challenging for HTA bodies to really determine whether that new option brings added value to the patient. Definitely. And that we're talking about small patient populations which mean limited trial data and obviously also uncertainty in the outcome. Yeah, absolutely, yeah. And then you've also got, you know, the, the high unmet need, like you said, iro, there's no comparison, no autonomous treatments out there. They kind of go going solo with this new therapy in very life limiting conditions. It must be very, very, I suppose, almost like a juggling act in a little bit of a way thought, you know, having a high unmet need and no alternative treatments are available would be a good thing for a manufacturer. No. Well, that also brings the issue of the high therapy cost. So a lot of these treatments are very expensive and it can be challenging for HTA bodies to be willing to cover the costs. So sometimes the unmet needs, unfortunately in reality might not be sufficient. To bring those treatments to the market. That is a heck of a point. And we're almost thrown into that really dangerous question was, you know, how much is a human life worth, which people have to juggle with? I mean, I don't want to be. I would hate to have to juggle with that question. But that is something that people have to think about, isn't it? That very, very difficult threshold. And that's why it's important to find ways to capture the value in HT assessments. And when we also think about rare diseases, there's so many unknowns and there's so much heterogeneity within each rare disease, which makes it even more complicated to bring out meaningful outputs. We've obviously got challenges and the challenges that I think AI and technology are helping to address, but as we've laid out, they're not things that can be easily fixed and they're things that potentially will always be a problem until we live in some very futuristic society. But it's the way that we deal with these things and the way that we put process and systems in place that help us get the best outcome. And that's why we want to talk about the EUHTA and the joint clinical rollout. Because at P5 we see this challenge daily, especially when helping companies prepare evidence strategies or using a brilliant tool like PWAY plus to analyse HTA decisions across Europe. So the question becomes, how do you make fair decisions when evidence is limited, but the need is urgent? So what should HGA do differently for rare diseases? Zero. Big question. Sorry, but you are an expert. Big question indeed. So with the EUG joint hta, we have this value of a standardized framework to assess evidence. And as we talked about about previously, the evidence that's generated in rare diseases is potentially the first time the joint clinical assessments will see that evidence. The endpoints might be unfamiliar, so there will be a need to retain some flexibility to make sure that we don't prevent valuable treatments from reaching patients. The other aspect of the Eugene clinical assessment is that they're including a lot of stakeholders that are experts to give input across different stages of the process, including experts who can provide insights reflecting patients preferences and lived experiences. So this will be particularly valuable for rare diseases. However, when we think about that framework on stakeholder involvement, they there's strict conflict of interest rules which might make it particularly challenging to implement in the rare space where the expert pool is considerably smaller. So again, greater flexibility in managing these conflicts of interest could be valuable to make sure that we bring those best Place to present patients in the conversation and not exclude them from participating. Well, fantastic answer. That's why she's an expert, folks. I guess what it does, Georgie, is it comes back to this patient voice, doesn't it? Yeah. Was saying, you know, the stakeholders, they get that information really from the patient. Well, yeah, yeah. I mean, listen, who is the expert in their own condition? The patient is the expert in their condition. They know what you know, they know their symptoms, they know their conditions inside out. They know what symptoms matter the most. They know what treatments benefit. What treatment benefits are meaningful and what's not. And they understand the risks sometimes because unless there's a patient advocacy group, you know, or there's a lot of information online, but sometimes it's, you know, it's so rare, like the ultra rare space. Actually, it's the patients themselves that start a patient advocacy group or the mum, or obviously you know, a child or someone like that. So they then become the expert. You know, they do know the risks to an extent, and, and they know what quality of life really looks like. Why are we not involved in them more or are we involving them? All our HTA assessments now really, really incorporating that patient voice, because in rare diseases, these insights are critical, especially when stress. Traditional endpoints don't always capture the real impact. You know, for example, just thinking. I'm just thinking on top of my head here, guys. But a treatment that allows a child to sit upright, for example, or a therapy that can reduce the amount of times you have to do a hospital visit, or a drug that actually lets a child attend school or somebody attend work, you know, these outcomes, they might not sound dramatic or they might not, you know, feel huge, but actually they transform people's lives and it's their quality of life. It's not just that person, is it? It's. It's the family. Can you imagine having a child who wants to learn, they want to go to school, they miss their friends. That's something they'd always new and then they can't. They're sitting at home and we all know what it was like. All the parents of us know what it was like in Kobe during lockdown. It was really tough. We were healthy to an extent, you know, but we didn't have children suffering from a rare disease. So, you know, for something to give you that relief that a child can go back to their life and that you can go back to your lives is absolutely massive. And it's very, very hard to understate that. So, you know, we've got Organisations like Rep, Patient Voice and many other advocacy groups, and they've shown how structured patient input, and that is things like understanding what they're going through and how something can alleviate that can really improve research design. And HTA submissions, these things are real and they're happening now Across Europe. We're seeing HGA bodies increasingly include patient testimony, which is massive, which we've just been talking about. That's the thing that I think we've all been clamoring for. You know, ask them, find out what's going on. Why wouldn't you? Also patient reported outcomes, which I think is very similar to testimony, but in a much more structured manner, and then also advocacy group evidence. So again, the groups that support patients, which is a multitude of different stakeholders, but there's still work to do. How has patient input changed an HTA outcome? You've seen eero, is there a particular example you can point us to? Yeah, absolutely. So, as part of research we conducted and presented at ISPOR in Glasgow, we focused at looking at two types of patient inputs. So, as you mentioned, patient reported reported outcomes, which are measured as formal endpoints within clinical trials, but also supplementary patient inputs, including feedback provided through patient surveys, discrete choice experiments and patient advocacy group submissions. What we saw, and what was very reassuring to see, is that where patient reported outcomes were available and robust, they directly influenced HTA outcomes through incorporation in the economic analysis of the UK and Australian HTA bodies. A specific example in a rare disease where we saw this direct influence was in the HTA of hemgenics A gene therapy available for the treatment of hemophilia B, which is a rare disease. Unfortunately, the supplementary patient inputs that we did find only had an indirect influence, so not specifically including them in economic analysis, but giving at least contextual information. So there is still some room for improvement in this space. So what can we do to make patient input real and really impactful in HDA decision making? Georgie? We've got a few practical steps that we discussed and we thought about. What were the ones that you think are most important here? I'd say, not that I'm the expert or anything, but just from my experience and the work that we do, I think the very first one, I mean, we say it a lot and I hear it a lot, is early engagement. Patient groups should be involved in the trial design, you know, right from the beginning, endpoint selection and evidence planning. And just to add to that, there is always opportunity to involve patients throughout the stages of the development of a drug. But the earlier you start, the bigger an opportunity there is, but if you haven't included it at the beginning, you can always find additional points to include that. Totally agree. That early engagement is so important for me. If I was someone said, look, we wanted you to be involved in trial design, endpoint selection and evidence planning. I'd be like, oh my God, it seems really, really complicated. How can patients sort of navigate these really complex things that people have trained years to understand. That comes with support from the clinicians themselves that introduce them to these experiences rather that might be unfamiliar also when it comes to the development of tools like these. So for example a discrete trace experiments, it should be developed in a way that's easy for a patient who's not familiar with these sorts of tools to understand. Great answer. Thank you very much. I've always wondered that. That's really, really good. And I guess, you know, it's, it's an engagement, isn't it? It's not necessarily being the person in charge of the trial, but it's putting input into that which is the important thing. It's understanding their point of view. You have to think about it, I mean the, of a clinical trial, it's, it's not just, you know, it's not just three months and job done, this goes on for years. This is a long time. And even once the trial's finished, you're still then part of the trial and collecting real world data. You know, you still have to maybe go monthly, quarter, whatever it is, but you, you'll still have to, you have to get to the clinical trial parent had to take time off work the trial center of excellence. You don't know where that could be. It's not on your doorstep. You might have to travel quite far to get to that place, maybe have to stay over. It's all of these kind of the things that have an impact not just on the patient, but on the caregivers and the families. So by incorporating them into that clinical trial design one, you're making sure, you know, they're going to adhere to it, they're going to stay, they're going to complete it. You know, how many patients do we see dropping out of trials because it's just not feasible for, you know, they just can't capture that into their normal day to day living. It's very difficult. And also in, in the rare disease space, you know, especially gene therapies, you know, they could be quite scary for some patients. You know, you hear the word gene and you think, oh my God, my child's going through this brand New treatment that's never been done before. I'm actually quite scared. Yes, I want my child to get better, but they have no options. There's nothing else out there for them. So what are their choices? So all of this has to be really thought about and taken into consideration, you know, from the manufacturer's point of view. And like ERA said, the earlier you can engage, I think the, the chance of you outcomes just increase, you know, by and by, and the more companies are involving the patients from the very beginning, you know, hopefully in five years time, we won't be sitting there having these discussions. We'll be sitting there going, yes, it's there. We're, we're, we're at that point, you know, the patients are part of the process as standardized across the world, not just in Europe, not just in the us, everywhere. So there's patient equality, which I think again is really, really important. Equity in rare diseases is, is very hard depending on where you come from, what background you are, how much money you have, what country that you're living in, whether they have, you know, the proper HTA body set up in that particular country and whether you even get access in that country, you know, it's huge. And ultimately, I think what, what I want to see is a world where everybody has access to treatments. Doesn't matter where you are, what age you are, how much money you've got, you know, a world where if you're ill, you can access treatment and have a better quality of life. She laid out a lot of information about the challenges of dealing with rare diseases. And we said early engagement is a great start to a practical step to making patient input real in HTA decision making. But Eero, could you think of anything else that is a practical step that we can implement? I would say education for HTA bodies and as Georgie touched on incorporation of patient input in the processes themselves. So it's very important to make sure that the decision makers have the necessary context to make a correct decision. And that comes through the involvement of patient experts, as we've mentioned in the eu, joint hta, more disease awareness from patient advocacy groups. So it's really a joint effort. It's working together, isn't it? It's that collaboration and having a bit of understanding, I guess, as well for, and compromise all these wonderful things that, you know, a lot of us seem to have forgotten in our lives. And these are the things that really make partnership really valuable. So let's hope to see those things because without the patient voice, you know, we risk, measure we risk measuring the wrong outcomes and making the wrong decisions, which I'm sure has been done many times before. Yeah, and that's exactly my final point. Oh. The partnership is making sure industry, HTA bodies, patient groups are all working together for the same end goal. And I think we are, it's starting to get better from where I started many, many years ago in healthcare we are seeing changes, but I think the rare disease community need them faster then, you know, we need this change across the world. Where we were five years ago, you, and you're a great person to ask this, Georgie. We were five years ago, we were, you said, we asked these questions and we've asked these questions again. Is there hope for the future in what's happened over the last five years? Is there a reason for optimism for where we were to where we are now, do you think? I think so, I think so. I think just through different technology, but I think even with the world of social media and the world we live in, where you can access knowledge quite quickly, quite easily, I am optimistic, actually, Owen, I really am. And I even think back to, I'm going to just say a real personal story here really quickly, but I think back to. So you may have heard it, guys. You know, I put some stuff out on LinkedIn just to our audience, but you know, my dad, my dad's side of the family were diagnosed is a genetic condition, familial hypogholesterolemia, type 2a. And none of the men on my dad's side of the family lived over 40. They, they had heart attacks, very, very young, fatal heart attacks. And again this was, they didn't know they had the condition. It was only once. My, my dad's dad died when he was, I don't know about one. All of his brothers passed away. You know, I think my dad had his first heart attack at 19, like a huge, he had a quadruple bypass at 25. And then they start thinking, okay, maybe there's something going on in the family, so we'll test but you know, it's not a rare disease but, but it's a, it's a genetic disease and, and you know, maybe 200 000, I mean I don't know how many in the worldwide there are but, but it's, it's not quite classed as a rare disease but I know from, from a personal impact, you know, my father passed away at 35, this massive heart attack at home and living through that and being the family on the other end of that and just what that does to a family is, is absolutely devastating. And I want to see that changing. I want to see that, you know, there is actually gene therapy in process for, for this to change that defect, to stop people dying, you know, you know, really early. So I am optimistic. I do think things are going in the right direction, just not fast enough for my liking. But we've got to start somewhere, haven't we? We do. And we are seeing advances in gene therapy, better registries, data collection. Yeah. There is enhanced collaboration across Europe. We're seeing that with EUHTA and stronger patient advocacy networks. Since I've started working in this space, I've definitely seen that improve. But iro, what gives you hope for the future? I think the fact that we're talking about this, about us having this conversation and so many other people doing that at the same time, it really makes me hopeful that this matter becomes an even more pressing one and patient voice becomes more central in assessments, ultimately helping to bring more patient centered treatments to the patients. That's a great way for us to finish. Thank you so much, iro, for your time and your expertise today. It's been wonderful having you on, Georgie. I wish you lots of luck and love and happiness for your forthcoming nuptials and on this rare disease day. Let's remember one thing, we've touched on it before, but it's a great way to end that. Rare diseases may be individually rare, but collectively common. Every statistic is a person. Absolutely. And behind every HTA decision is a life changed. And I like that. I like to end on that. It's powerful. So from all of us at parks for Access, thank you to the patients, advocates, clinicians, researchers, scientists, everyone involved in the development and treatment of rare diseases. You have our appreciation and our thanks. Now, if you'd like to learn more about Parks for access work on Euhta orphan drug access Pico plus, visit partnersforaxis.com incredible resource, loads of stuff on there. And you can also listen to loads of our old podcasts, so please do. We are also hosting an access summit taking place on the 14th of April in Zug, Switzerland. And I know Georgie Rack has got some more to tell us about that. I do, absolutely. Thanks, Owen. So this year, guys, we are focusing on the most favored nation, which is the latest U. S Policy that's coming out. And if you know what that means and you don't understand it, you need to be at our access Summit in Zug in April. There's lots of information on our website. So again, do go and have a Look, if you go under our Insights page, you'll find the P4.8 Access Summit 2026. Lots of information there guys, and a registration form. So it is going to be the event of the year. I'm not just saying that. So I really do, I really would. If you're not sure and you don't know how to navigate this from the manufacturing side, then this is the event for you. We hosted one last year. It was a sensational success. And the great thing about the Zug Access Summit is it's just a one day event. It is packed a huge amount into one day so you don't have to worry about, you know, booking lots of hotels and other things like that and buying your kids presents after you've been away for three days. You can come for one day and absolutely learn an incredible amount. So check it out. Go onto our websites and check out LinkedIn for some updates to the Access Summit too. Perfect. And most importantly, I can't forget, keep listening to the patient voice, guys. And Happy Rare Disease Day. Thank you for listening to the discussion. You can find more information about this subject and other matters relating to rare disease and cell and gene therapies on the Insights section of our website. Www.partnersforaccess.com Sat.