Rare diseases: from lived experience to lasting treatments | Sponsored

0:00Hello and welcome to this special podcast brought to you by the New Statesman Spotlight team. We cover policy for those who shape it and the businesses it affects. I'm Sarah Darwood. A rare disease is defined as a condition that affects fewer than one in 2,000 people, but as we'll learn in this episode, their cumulative effect is anything but rare. These to mark rare disease day on the 28th of February, we're asking why these diseases, affecting 1 in 17 people in the UK, still leave many families facing years of uncertainty despite treatments and therapies being identified. This episode has been fully funded by Lifehark, a not-for-profit medical research organisation that turns promising scientific research into breakthroughs. Joining me on the panel today is CEO of Lifehark Sam Barrel and Terry Pirovelakis, whose

1:03son Michael has SPG 50, a neurological disorder affecting fewer than 100 people in the world. Welcome to you both. Thanks so much for being here. Terry, could you start by telling us about Michael's diagnosis and your family's journey? Absolutely. Yeah, so thank you for having us. Michael was born in December 17, 2017, a normal healthy birth. We were home within 3 hours and we thought we would start our lives together with our other children. Around 6 months of age, we noticed he wasn't lifting his hands, he wasn't lifting his head. So we went to the doctor's office and they said, don't worry about it, he'll just grow out of these kind of things. Go see a physiotherapist that might help and continue along. About 2 months after that, my wife continues saying, you know, Terry, something's wrong with Michael. We need to do something more. So we went to the pediatrician's office. We diagnosed him with low muscle tone as well as Microsoft, I believe his head was not growing at the World Health Organization's levels. They said that again, children have this from time to time, they grow out of it, nothing

2:04to be concerned about, but just keep an eye on them. A month after that, again, we went back to the pediatrician's office and we said something seriously wrong and we were instead infectious diseases at sickids in Toronto because I was doing a lot of work in Latin America at the time and they thought maybe I contracted Zika in somehow gave it to Michael and that's why he was having these issues. We did all the panels, we did all the infectious disease testing and they found nothing was wrong with Michael. So we were sent to neurology, neurology did an MRI. They found that he had severe microcephaly at this point and after a genetic test, they found that he was diagnosed with SPG 50, or spastic peripolegia type 50. Thank you so much for sharing, Terry, that sounds like such a difficult journey for your family to have to go on. Yeah, it was an 18-month diagnostic odyssey, that's for sure. Most families nowadays are diagnosed much sooner because of improved testing and different technologies. But yeah, I think the hardest thing was, on April 2nd, 2019, Michael was diagnosed hearing

3:06that he'll never walk, he'll never talk, that he'll have a short lifespan and there's nothing that we can do to change the course of his disease, to go home and love him and give him the best life we possibly can. Absolutely, and it sounds like you really pushed as a family to try and get to the right diagnosis and get the treatment that he needed. Sam, I wonder if we could come to you. So rare diseases, as we've said, affect around one in 17 people in the UK, yet many remain very poorly understood, underdiagnosed and under-treated. Why do you think progress has been so slow in this area? Well, as Terry said, one of the problems is it takes an awful long time to get diagnosis. In fact, about a third of rare disease patients weigh up to five years to get a diagnosis. And as you say, rare is not rare. About 3.5 million people in the UK suffer from a rare disease. That's roughly the same number as people who suffer from cancer, and yet 95% of them do not have an approved treatment, and 80% are genetic in origin, and 70% are presenting

4:09childhood. All for a lot more we need to do to really understand rare disease and make sure we get treatments and support to people like Terry and his family. I mean, I'd be interested to know from both of your perspectives, really, where you think the biggest gaps are both in the healthcare journey for families and in the wider healthcare system. There are several gaps identifying and diagnosing people with rare disease. As we said earlier, around a third of people weigh more than five years for a diagnosis. There's a lack of joined-up data, so we can't necessarily easily identify people with rare disease, and also it means we can't actually identify the true costs of rare diseases to the healthcare system. There's also a gap with making new treatments available, getting treatments developed, tested at trial, and then to patients is really challenging, even for normal medicines. And for the rare disease treatments, there's small population size. We haven't got necessarily the data easily available. And we need a more innovative regulatory approach with our national regulators.

5:14There's a lack of investment because of the potential lower commercial return. And from your experience, Terry, would you agree with that? Do you think that's where the biggest gaps are or would you add others in there as well? No, I think it comes down to cost at this point. I mean, I think it takes on average a billion dollars for a pharmaceutical company to create a therapy. And if 95% of those are 98% of those are failing because of requirements that are just unachievable, then we're never going to get there in these diseases. We need to be able to make these drugs faster and cheaper. We need to have a lower bar or maybe a different variables for ultra-reconditions that are applied today at the regulatory bodies. You've both kind of touched on Terry, especially with your personal experience and your family's experience, that diagnostic odyssey, that journey that you had to go on in order to get the right diagnosis, it sounded really difficult and very hard for you as a family. What do you think the main barriers to earlier diagnosis are and how damaging are these delays for the patients and families, Terry, did you want to start?

6:15Yeah, I would say that in a lot of, like I live in Canada, for example, in Canada, you have to go see a specialist and there has to be a step up, so you have to do like these things called panels, so you have to do an epileptic panel, then you have to do like a spasticity panel, for example. And then you can go to whole exome or genetic screening. So, you know, there's a lot of these insurance barriers and government barriers where you have to meet this criteria. Now more and more, that's becoming less of a problem, for example, in Spain, if a child comes in and they don't know what that child has, within the first blood draw, they're doing a genetic sequence. And I think that's probably where we should all be going, but yeah, there's these limitations where in governments, you have to go from your doctor to a pediatrician to a specialist and that could take 12 to 18 months just to see someone. And Sam, did you want to come in on that as well around those delays to diagnosis and as Terry's just mentioned, that delay to even seeing someone in the first place? I mean, I would completely agree with Terry that we need a much more systematic approach to diagnosing red disease early and Terry's point about genomic testing would be a very

7:18effective method, particularly with the fact that 80% as I said earlier, of people that suffer from a red disease have a genetic origin, so I'm welcome, the NHS 10-year plan that's talking about widespread newborn screening, but it isn't yet in place yet. There are some pilot schemes that are in place, but this could be transformative in picking up children earlier with a red disease and then getting them treatment much earlier, because often as the red disease goes on, some of the damage it does and the illness that it causes can be very difficult to reverse, even if you get treatment to a child at a stage. So what we need is early fast diagnosis and early access to treatment where treatment is available. And of course, there are 7,000 red diseases and treatment isn't always available, but at the moment families feel very lost, very abandoned, so not only may they struggle to get a diagnosis, but once they have a diagnosis, they are often left to not know what to do next. And I think Terry's got a very compelling story about what he did next when he finally

8:20got a diagnosis, which is quite extraordinary. So really what we need is families feel much better supported and at the moment in the NHS and other healthcare infrastructure, red disease is not thought of as mainstream medicine. It's an afterthought. There is not care pathways, there's not services that allow people to access specialist advice rapidly and quickly in order to get their red disease more effectively treated or supported. Terry, the journey you've been through sounds so difficult, but also remarkable in terms of what you and your family have done in order to get your son the right diagnosis and treatment. Can you tell us in detail a bit more about your story? Yeah, so Michael was again diagnosed April 2nd at 2019. We went home and we lost our minds. I was crying on the street when they read to come pick me up. Meanwhile, I've said we have to do something, so I locked myself in a room. For 24 hours, I came out and I realized that a gene therapy is what we need to accomplish. Told my wife, we have to raise three to four million dollars, that we might have to sell our home, that we're going to liquid airline savings, and that day we started that

9:22journey. That day after Michael was diagnosed, we found an amazing team of two researchers, Dr. Steve and Gray and Dr. St. Chen out of UTSW and Dallas, Texas. We gave them the initial funding. They made the gene therapy for us. We then raised four and a half million dollars over four years through gallows and gall tournaments and bike rides and you name it. We did it. And three years after Michael's diagnosis, he was treated as sick kids in Toronto the first child ever to be treated at the hospital through precision medicine. And it was just a crazy journey of luck, teams and community support that came around and said, we are not going to let this little boy suffer and now, thankfully, from this amazing journey, we treated 11 children and we planned to treat 38 this year. It's really remarkable and I'm so sorry for what you've gone through, but it's amazing really the level of, you say luck, but it sounds more to me like perseverance on your side. You need to have a thick skin. You need to be, you know, not anything bother you and just go forward with everything

10:24that you have humanly possible was, it was a very tough journey, I'll admit. But again, we had an amazing team, we had an amazing support system and and we're blessed to have such an amazing people around us. Obviously your experience is very unique to you, but I guess I'd be interested to know from from both of you to what extent you think your story Terry reflects the challenges that are commonly faced by other families confronted by rare diseases. Do you think it's a common experience what what you went through? Yeah, I mean, I got, I got 15 calls a week and it's a very common experience. I mean, nowadays, luckily, genetic testing is being offered much earlier, but they have the same, the same problem, their diagnosis are told, their child has, you know, 10 years to live, that there's no treatment, there's no drug at all. And the go home and love their child and it's the wrong answer. The answer should be that we have a path forward to help these children and give them a better life when we know what these genetic conditions in a lot of the cases, we can do something. And unfortunately, we're financially bound by these rules and these constructs that are

11:27limiting us from being able to treat these children. Thank you. And Sam, what do you think from your experience of working with families who are dealing with rare diseases, to what extent do you think Terry's experience is reflective of the wider community? Oh, it's absolutely reflective. I mean, families have very little support, often actually very pleasingly, there are lots of rare disease charities, often that parents set up or families set up themselves, having had a, you know, very devastating experience with rare disease that end up being hugely supportive for people that have been diagnosed with a rare disease. And there's many of these charities, both in the UK and internationally, but ultimately, not only do you want a diagnosis, not only do you want support, but you want access to treatment, if there is the possibility of treatment as Terry alludes to, and that's what Terry successfully made happen. But at the moment, there can be therapies, but you can't necessarily get access to them. There's also some great success stories, I mean, the success story, the other day that

12:27was reporting the media about Ollie Choo, the little boy who had Hunter syndrome, where the scientist Simon Jones and Brian Bigger managed to create a gene therapy. We funded it as the charity through trial, and that little Ollie's showing to be making remarkable progress. But there is hope, there is diseases where we understand the biology, there are scientific mechanisms which we could deploy to put treatments in place. And some of the things that are getting in the way are, as Terry says, investment routes, complex regulatory and reimbursement pathways that need to be simplified. And basically, people being more aware of the sheer devastating consequences of these diseases, and it becoming more mainstream that this is not acceptable, and that these people need help, and they need help much faster than they get at the moment. And as the example you've just given that was recently in the news, and also with Terry's example, we're seeing then this role of parent shift, not just to being kind of a parent

13:27and a carer, but also to an advocate and a champion, and actually finding those research solutions and sort of doing that research themselves. How do you think that shifting role of parents and families is impacting research and treatment development? And I guess most importantly, should parents have to be doing this? In my opinion, absolutely no. I mean, actually, Terry's story and other parents that have achieved what Terry has achieved. I mean, they're incredibly remarkable people, but if you're faced with a new diagnosis of either yourself or a family member with a potentially devastating rare disease, the last thing you need to be thinking about is how an earth can I access treatment pathways, how can I navigate the health care infrastructure, how can I get better support for my circumstances at home with that particular person who's got the illness, what you should be able to do is just concentrate on your family or your friend who has the illness and help them support them the best way you can. And at the moment, this is a very frustrating and very stressful experience for most parents

14:31or families that are in this situation, and it really isn't acceptable. Terry, it'd be great to hear from you. Where was the point that you realised in order to make progress, you would have to become an advocate and an organiser yourself as well as a parent? Yeah, certainly that on the head, we shouldn't be doing this. This is not something parents should be doing. And for me, unfortunately, it was the moment they told me to go home, love, and there's nothing you can do. That's when I knew I had to do something. And then the next day I went to the hospital and I was emotional and I was like, I'll give the hospital four million dollars, please help me make this therapy. And there were, we're just not capable of doing this. This is not something that we can just make for you. And at that point, I knew I had to do something. And that's when the journey really began. As we've spoken about, often the commercial incentives are weak in this area of red diseases. And that's the area in which life arc and organisations like life arc operate in. Why is the charity sector so important for red disease research, Sam?

15:31To be fair, I think every sector is important because really what you want is a joined up solution that gets to the patient in the end. And for that, you need organisations like life arc, charities, not-for-profit organisations. You need specialists, science companies like biotech companies and pharmaceutical companies to get the therapy finally to the patient. And you also need government bodies because you need the government and the regulatory bodies and the healthcare infrastructure to all be joined up to make the approach much more effective. And at the moment, we've got individual organisations contributing something towards making things more joined up. But we've not got a really systematic overall joined up system. And if you compare it with something like cancer and I'm not saying that having cancer diagnosis is any less devastating, of course it really is. But there is a much more joined up approach to early cancer diagnosis with rapid access treatment pathways. And there's a much more holistic approach to supporting people with that particular diagnosis.

16:32And so we need that kind of approach for red disease patients as well. We know that the government has put a lot of needed focus on reducing the prevalence of diseases like cancer, diabetes and heart disease through its major condition strategy. As you've said, this is obviously hugely important as these diseases impact so many people, they affect their health, their quality of life and their life expectancy. Do you think then that the government needs to start treating red diseases considering how common they actually are with a similar level of importance? Absolutely. And in a way, that's why we convened that red disease task force of experts last year to bring together a port to ask the government to do four key asks, which we think would make a difference in the future. One of those is improving data and diagnosis. One of those is supporting innovators for developing treatments, making new treatments available. But also the key point is a national champion for red disease. And that national champion should be able to coordinate across the system to try and make

17:33this more mainstream and as important as other diseases that impact people severely. And what would that national champion role look like? What would they do on a daily basis, for instance? Well, what we'd like is a much more coordinated approach between the not-for-profit sector, key red disease charities, the hospital systems, primary care, the regulators and the reimbursement regulators so that we can basically get a much more innovative and agile system for people with red disease. They can get diagnosed earlier, they can get access to treatments early, if treatments are available. And at the very least, they can get proper support. And Terry, as a parent, what's the biggest change or policy change that you would like to see? Is it that national champion's role or is it something else? I think that the national champion's role is an excellent idea. I think we also need governments to start reducing the requirements for ultra-reconditions in regards to meeting endpoint efficacy as well as getting to the end, getting to approval.

18:37I mean, the bar is so high that red disease programs mostly fill at that very end stage. And then I think funding, we need a lot more funding in order for us to be able to take on not just one or two or five red diseases, but take on hundreds so that when a loved one that has Parkinson's AOS Alzheimer's that are multi-genetic diseases, we will have learned from these terrible diseases in children, how to treat those diseases that will afflict every one of us that are multi-genetic. If there was one thing you'd like people to know who are listening at home, what would it be? Yeah, when I saw people with red diseases and they were, you know, I had children in wheel chairs and everything else, I was like, those people are so strong. And now that I'm a rare disease parent, I got to say that this is the hardest thing you can ever do. And if you have a family member or a friend or a neighbor, anybody that has a rare disease that you know of that's already gone through tough times in the disability, buy them a

19:37coffee. You know, it's really difficult having a child or a family member that has a rare disease or an illness. And I would say just, you know, buy them a coffee, just listen, because it's a really tough thing to go through and sometimes people just need that extra support. I would encourage you a way to do that. And Sam, what would be the main thing you want to tell people at home? As we've heard, if you suffer from a rare disease or you're a parent or a family member or a carousel of your rare disease, it is utterly devastating. These are really serious diseases that often shorten lifespan and can result in severe disability. And what I hope the audience will take away from this is there is hope, there is possibilities of treatments, we certainly ought to be able to improve diagnosis, we should certainly be able to give far better support. And there's some good economic imperatives for this as well. The loss to the economy currently in the UK annually by us not acting is 15 billion pounds a year.

20:39If only we could step in and take a much more coordinated approach and really mainstream our approach to rare disease like we do other diseases, we can make a huge difference right here and now. Thank you so much. Thanks to our panelist, Sam Barrel and Terry Pirobacolis. You can find more coverage of Spotlight's policy reporting at newstatesman.com forward-slash-spotlight. My name is Sarah Darwin and this episode was produced by Sue's Cooper. Thanks for listening.