Rare diseases: 1 billion reasons to care

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Antonio Estrella, Lead, Health For All, Centre for Health and Healthcare, World Economic Forum: You might be one of 10 families in a given country that have that specific disease. But there are more than 7,000 rare diseases that affect more than 300 million people globally. And when you add in the families whose lives are touched by being able to support their family members with the rare disease, we're looking at a billion people in the world

Robin Pomeroy: When does the word “rare” describe something that affects the lives of a billion people?

Will Greene, Board Member, Foundation for Prader-Willi Research: Many of these families will spend years going from clinician to clinician, from health centre to health centre, often incurring tremendous cost, often incurring great emotional problems along the way.

Robin Pomeroy: Welcome to Radio Davos, the podcast from the World Economic Forum that looks at the biggest challenges and how we might solve them. This week: what are rare diseases, and why could paying more attention to them have knock on benefits to all of us?

Alexandra Heumber, CEO, Rare Diseases International: We often say actually that by fixing rare diseases in the health system, you actually fix the health system itself.

Robin Pomeroy: We hear from campaigners who have helped secure a global agreement on tackling rare diseases, from someone whose life was changed by rare disease in his family, and from the private sector which also wants to see advances in the field.

Soraya Bekkali, Senior Vice President, Europe, Canada & International, Alexion, AstraZeneca Rare Disease: Those patients are invisible in their own healthcare system. They are invisible of to their government, to their ministry of health, because of the insufficient data

Robin Pomeroy: Follow Radio Davos wherever you get your podcasts, or visit wef.ch/podcasts where you will also find our sister programmes, Meet the Leader - great interviews with some of the brightest leaders from business, academia, civil society and the arts.

I’m Robin Pomeroy at the World Economic Forum, and with this look at rare diseases...

Will Greene: It's something that can impact any family, sometimes at any time.

Robin Pomeroy: This is Radio Davos

Robin Pomeroy: Welcome to Radio Davos, the podcast from the World Economic Forum that looks at the biggest challenges and how we might solve them.

This week, the challenge we're looking at is rare diseases. And to help us talk about that, I'm joined by a co-host, my colleague, Antonio Estrella. Hi, Tony, how are you?

Anonio Estrella: I'm doing very well, Robin. Thanks for inviting me to be a co-host on this show.

Robin Pomeroy: It's great having you as a co-host. You and I have done three really, really interesting interviews about the subject we're talking about today. Before we get into those, tell us what exactly you do at the World Economic Forum.

Anonio Estrella: Well, I'm honoured to be part of the World Economic Forum team within the Centre for Health and Health Care. Within that organisation, as many of your listeners may know, we organise the effect and change we want to create in the world by initiatives. And so I lead one of our initiatives called Health for All, where, put simply, our goal is to help change the fact that there's an uneven distribution of health and health care resources, especially across chronic diseases or non-communicable diseases that lead to having different health outcomes depending on where you live and where you work or what kind of disease you're dealing with.

And so the rare disease community and this focus on rare diseases is part of the work that we do in the Health for All initiative because it's a disease area that doesn't have the same level of attention as other what people might see as more visible diseases such as cardiovascular health or cancer but it is very impactful and needed for us to put a spotlight and attention to mobilise resources and a coordinated effort to address the lives of people living with rare diseases.

Robin Pomeroy: Rare diseases, unless you are directly touched by one of these diseases, you might not really be that familiar with what a rare disease is. Tell us what we mean by rare diseases.

Anonio Estrella: So there's a technical definition where you can look at it across the region, say in Europe, where it's less than one in 2,000 people that have a rare disease, or in a country like the US, collectively across rare diseases, it might be 200,000 in the US with the rare disease category.

But when you change that lens to look at from the family, you might be one of 10 families in a given country that have that specific disease. And that means that there's just not a lot of people like you.

The real opportunity to look at why rare diseases matters is that when you look collectively across the rare disease community, there are more than 7,000 rare diseases that affect more than 300 million people globally. And when you add in the families whose lives are touched by being able to support their family members with the rare disease, we're looking at a billion people in the world who are affected by rare diseases.

And that's why this category really matters to be able to have greater attention from resources, from governments and for innovation.

Robin Pomeroy: More than a billion people's lives are touched by rare disease. Let's hear from one of those billion, who's the first person we interviewed on this. Tell us something about Will Greene.

Anonio Estrella: So Will Greene is a board member for the Foundation for Prader-Willi Research, which is a patient advocacy group in the US who focuses on one particular rare disease. And while being a board members, Will is also a father of a son with Prader-Willi. And so it'll be a helpful way for us to be introduced to what it means to be a family dealing with rare diseases, because we can hear from Will who's actually living this all the time.

Robin Pomeroy: Let's hear from Will Greene then. We started by asking him to detail his personal experience.

Will Greene: My name is Will Greene and I am a board member at the Foundation for Prader-Willi Research. I'm a caregiver for a child with a rare genetic disease, and I am an advocate and researcher focused on the broader rare disease space.

Robin Pomeroy: Hi Will, great to meet you. I wonder whether we might start with your own personal experience. Could you just, you know, tell us what happened and and how that brought you to where you are today?

Will Greene: My journey into rare disease research and advocacy started unexpectedly, as is often the case for people in my position. It started with me becoming a father and caregiver for a child with a rare genetic disease.

Now, this is not something that I ever thought would happen. It's something that most people who end up in this position don't plan for. And I always assumed that I would have a healthy neurotypical child.

But when my son was born, and after he came out and we realised right away that something was not quite right. He was floppy, he couldn't cry, he couldn't drink, and he was taken away right away to the neonatal natal intensive care unit for further assessment.

Now, in the following days and weeks, we went through what is called a diagnostic odyssey, something again that is very common to people who become caregivers for rare genetic diseases, where we went through a series of tests and a series of consultations and a series of procedures to determine what exactly was going on.

And after one month, we got the diagnosis. We found out that our son had a condition called Prader–Willi syndrome, which is a rare and serious genetic disease that impacts development, impacts cognition, and impacts many aspects of human systems.

And so it was a very emotional experience becoming a caregiver for a child with a rare genetic disease. It was something that my wife and I spent a lot of time processing, but also it was something that was very catalysing and motivating because we didn't want to accept a future in which our child would face major health and social issues. We wanted to fight for a better future for him and for all the other children like him.

So that was a little bit about my journey into this status as a rare disease caregiver.

Robin Pomeroy: And it just so happens you were already working in healthcare, right? Th is kind of was your field, if not rare diseases.

Will Greene: So at the time that my son was born, I had already spent close to a decade working in various healthcare industry roles in digital health, in pharmaceuticals, and in diagnostics. And while I did have some industry experience that gave me a bit of a perspective on rare diseases, I can't say I ever worked deeply in the space.

And so while I heard about rare diseases, I had never really worked in them. And I never appreciated just how large an impact they have on families and societies at large. And I also didn't appreciate what a fertile ground for innovation rare disease research and innovation was.

And so even though I did have experience in healthcare, the journey into rare disease research and advocacy was also incredibly inspiring because it showed me that rare disease is often a very fertile ground for broader innovations that impact society at large.

Anonio Estrella: Thanks Will for sharing. I know it's such a personal event and you know we really appreciate you opening up to us about what that was like.

And you know, one of the challenges you mentioned is the diagnostic odyssey. And yours was a month long of not knowing what's happening and for the audience you they they should know that that diagnostic odyssey actually can be five years on average for people with rare diseases. Can you describe to us what that felt like and what it means as a caregiver?

Will Greene: So the journey from knowing something that was profoundly wrong with my newborn to actually understanding the condition that impacted him, in my case took a little bit over a month. And I can say that that month was one of the most gut-wrenching, heartbreaking months of my entire life.

And yet, once my wife and I got through it, and once we started to look more deeply at the broader space in terms of rare disease, we realised that in some ways we were lucky because many families go years searching for a diagnosis without ever having the clarity that provides emotional comfort and understanding that there is a clear explanation for what's going on, and also a jumping off point for searching for therapies and treatments that could make a difference in their child's life.

So for many of these families, they will spend years going from clinician to clinician, from health centre to health centre, often incurring tremendous cost, often incurring great emotional problems along the way. And so for many people, the diagnostic odyssey is one of the most challenging aspects of the rare disease caregiving experience. And that's why improving screening and diagnostics for rare disease is so critically important.

Anonio Estrella: And and building on that, once you found out what the challenge was, I know you had to make a geographic change in your family's life to be able to have availability, access and affordability of treatments. C an you describe what was your journey and how that applies to other families and patients living with rare diseases?

Will Greene: My son was born and diagnosed in Singapore, which is a country with a world-class healthcare system, but with a slightly different approach to insurance and reimbursement than many other advanced countries.

So in Singapore, unlike in many other Western countries, rare genetic diseases are not typically covered by employer-provided health insurance plans and not as deeply covered by public sector insurance as in other countries.

And so one thing that became abundantly clear after my son was born and diagnosed was that financially my wife and I were more or less on our own. And because often caring for children with rare genetic diseases and treating them is astronomically expensive, we realised that we faced catastrophic financial risk if we stayed in Singapore and tried to raise our child there. So my wife and I made the very difficult decision of leaving our jobs and relocating to the United States, where we believed we would get not only better care, but also better community and better insurance coverage to make sure that the impact of treating our son wasn't financially toxic.

And this is not an uncommon story. I know many other families who have had to change jobs, change homes, relocate geographically, sometimes across entire oceans, to get their children the care that they need.

Robin Pomeroy: What happened to you? Because I imagine anyone listening to this you know, will have found some health problem of themselves or of a family member, and they'll Google it straight away and try and find out.

You knew within a month the name of this condition. I'm quite sure you would have Googled it. But then after that, what did you find there was? Where did you find kind of good advice? Was there, were there communities of people? Were there organisations? Or were you kind of hanging, was there kind of a wilderness and a lack of support and advice? What what did you come across?

Will Greene: So our son was diagnosed with Prader–Willi syndrome, which is a rare but not ultra rare genetic disease. And there are probably a few hundred thousand people around the world who have this condition. And as a result, even though it's not as well characterised and understood as more common conditions like diabetes or heart disease, there was already an existing community of researchers and advocates and families who had already come together and mobilised resources and built organisations to help address the needs of the Prader–Willi syndrome community.

And so, in some ways, I was very lucky that I was able to plug into this community right away for knowledge, for emotional support, and for a sense of hope for the future that people were out there working on solutions for a problem that was very challenging.

Now, not every rare disease family gets that kind of support. There are many conditions that are much rarer than Prader–Willi syndrome where there is no established patient community, where there are no clinical investigators and trial sites and things happening that they can immediately plug into. And so a lot of families who find themselves in that situation often deal with incredible uncertainty, but then in some cases get mobilised and build those communities from scratch.

And one thing that you'll find in the rare disease community is that you find people who have a sense of urgency and a deep motivation to find solutions for the challenges that impact their families. And this urgency and this motivation often drives incredible progress.

Anonio Estrella: So you're you're in that space now with a foundation that brings all that together. Can you tell us more about how this foundation is advancing, not just in Prader–Willi, but across rare diseases, a focus of innovation and bringing that together to be able to drive impact for people's lives.

Will Greene: So the Foundation for Prader–Willi Research, the organisation where I serve on the board is one of several large, well-funded and well-established Prader–Willi syndrome patient groups. And so I can speak specifically to the Foundation for Prader–Willi Research and what they're working on.

The Foundation for Prader–Willi Research has been around since 2003. It has been focused exclusively on developing treatments and eliminating the challenges of Prader–Willi syndrome. And over the years, it has invested well over $28 million in research and research tools and community-building exercises that have helped to really change the landscape of Prader–Willi syndrome.

So a few decades ago, Prader–Willi syndrome was a condition that was profoundly debilitating for nearly everybody who suffered from it. These are people who could never even dream of having a job or living a long normal life.

And yet today, we have more hope than ever that our kids can grow up and live full and productive lives. And that is a function of scientific innovation. It's a function of research and data capture, and it's a function of therapeutic development that is slowly, gradually, imperfectly, but over time changing the landscape of the condition and how people with it live their lives.

Robin Pomeroy: Can I ask, how how is your son doing now and what have been the good and the bad things along the way?

Will Greene: Today my son is three and a half years old, and in many respects he's doing great. If you meet him, you may not even know that he has a genetic disease. And that's normal for people with Prader–Willi syndrome, because often the challenges that are associated with the condition tend to show up a little bit later.

And these challenges often become very debilitating for most families, and they force these families to sometimes live very alternative lives.

So one of the key features of Prader–Willi syndrome is something that is clinically referred to as hyperphagia. And this is a sensation of constant hunger that kids with this condition feel no matter what they eat, no matter when they eat, no matter how much they eat. And this is something that drives many of them to incredible feelings of anxiety. And in some cases it requires families to impose food security measures in the home to literally lock the fridge, to make sure that there's not food and garbage, and to prevent kids from overeating to the point of morbid obesity and in some cases death.

And so today my son is doing great. But still, there is a dark cloud that hangs over our future, and this is something that we are working very hard to dispel.

Anonio Estrella: When you say working very hard and what changes need to happen, can you describe what are some of those changes that you or believe need to exist, either in the form of what the foundation is currently helping to drive or more broadly from other stakeholder groups?

Will Greene: In terms of the challenges of the Prader–Willi syndrome and broader rare disease communities, there are two overarching issues that we are working very hard to overcome.

The first is a general lack of awareness and recognition from within healthcare systems.

There are a lot of families who don't get the support they need because the conditions are not well understood by their clinicians or by their school systems or by other key stakeholder groups that they interact with.

And then, more broadly, another big challenge that our community and almost every rare disease community face is a lack of adequate funding for research and for therapies and for services that are so essential for making sure that our kids can live full and productive lives.

And so one of the key things that we're working on at the foundation is driving research to create those therapies, but also driving awareness to ensure that clinicians and healthcare systems and payers and employers and all other key stakeholder groups who might impact the experience of a Prader–Willi syndrome person or family are sufficiently aware of the challenges we face and also the benefits of supporting our communities so that we can live the most full and productive lives that we can.

Anonio Estrella: You mentioned that the the impact that you need to create from the foundation is on health systems and improving education. The dynamics of driving change in health systems is complicated. And you know, as you've mentioned, not everybody is very familiar with rare diseases. So you've been working with us at the Forum on a new white paper. What are some example recommendations from this white paper that you feel can help to accelerate impact, and why why start with rare diseases?

Will Greene: Rare diseases are one of the largest unmet needs in healthcare systems globally. These conditions are individually rare, but they're collectively common. And when we look at the financial impact of these diseases, it's often measured in the trillions.

So we know that, untreated, rare diseases are a major drag on healthcare systems' efficiency and productivity globally.

So we believe that investing in rare diseases will help offset some of that cost impact. But in addition, what we know from the history of rare disease research is that rare diseases are fertile ground for research and innovation in terms of scientific understanding that impacts broader populations.

And so there is a long track record of innovations that were incubated in rare disease research settings that ended up ultimately having broad societal impact that was very positive across healthcare systems.

One example: genetic sequencing. This is now a technology that is routinely employed in healthcare systems everywhere. And people can get their genes sequenced often for hundreds or thousands of dollars. But that was not always the case. Decades ago, genetic sequences cost millions, and actually when they first started, it was even billions of dollars to get a whole genome sequence.

And so rare diseases were not the only application through which these technologies were refined, but they were one of the key drivers for further refinement of this technology.

The same is true in a very exciting and emerging category of medicine called genomic medicine. This is medicine where we treat the underlying genetic defect that drives some kind of health problem. And there are many different types of genomic medicine out there. There's RNA medicine, there's gene editing, there's gene therapy.

But in most of these cases, rare diseases were among the most important initial applications and testing grounds for these therapeutic modalities. And they helped drive improvements in these modalities in a way that ultimately has delivered benefits for the broader populations with more common diseases.

So rare disease is an incredibly important bedrock of scientific and healthcare innovation more broadly, and one that deserves substantially greater amounts of funding than what it gets today.

Robin Pomeroy: Is there one thing you'd wish the general public would know about rare diseases? When you come up to people who aren't aware even of that expression, aren't aware of the condition your own son has. Is there one thing you would just like us all to know?

Will Greene: Rare diseases are individually rare but collectively common. And it's something that people don't always think will happen to them, but actually almost all of us have some level of risk for a rare genetic disease. And it's something that can impact any family, sometimes at any time.

Now, many of these rare diseases often manifest in childhood, and we often are aware of these conditions early on, but there are some rare diseases that do manifest later in life too. And so for that reason and for many others, rare diseases matter to all of us.

Rare disease research and innovation is something that has great effects on society in terms of reducing costs to healthcare systems, in terms of driving innovation, and overall driving happier, more productive societies.

So rare diseases matter. That is my key message.

Robin Pomeroy: Will Greene, who's on the board for the Foundation for Prader-Willi Research.

So rare diseases affect vast amounts of people around the world, and that in itself is reason for us to be paying attention, as well as obviously the personal huge challenges to people like Will affected by diseases like this.

But there's another good reason for us to be paying perhaps more attention and putting more money into research for rare diseases, Tony, I think you were explaining to me about the knock-on effects, the ripple effects of that.

Anonio Estrella: There's a good history here of why innovation in rare diseases actually has broader impact. This has happened before.

So when we think about genomics and genetic screening and all the innovations around being able to understand the impact of your genetic history and your makeup and how we can learn from science to address your challenges, a lot of the initial research that was done in that space was done with rare diseases in mind.

And that led to what we know today as precision medicine in oncology and cancer and other areas where we're really looking at your genome to then provide better treatments.

A second example is in mRNA. That's a platform that many of us are familiar with from having an mRNA vaccine from COVID times. That platform also started with rare diseases as initial area of research.

And so what we're looking to do in building this community out is how can we look at data and innovation as another catalyst for looking at rare diseases first and then having broader implications across health and healthcare.

Robin Pomeroy: Let's go to our second interview now. This is Alexandra Heumber, who is the CEO of Rare Diseases International. And she's gonna be speaking about kind of the global push to do more on rare diseases. Tell us something about Alexandra.

Anonio Estrella: So Alexandra has been a huge evangelist for change, for being able to motivate and connect what governments are doing with other stakeholder groups.

And, as you will hear in this interview, the work that she's done over a 12 month period to be able to motivated governments to create a new resolution is amazing. So I'm looking forward to hearing her voice here.

Alexandra Heumber: I'm Alexandra Heumber, I'm the CEO of Rare Diseases International based in Geneva.

Robin Pomeroy: Alexandra, it's great to speak to you. Tell us what is Rare Diseases International?

Alexandra Heumber: So Rare Diseases International is the global alliance of people living with rare disease. So we are an umbrella organisation representing patient organisations across the world. We have one hundred and twenty members representing patients over 150 countries.

Anonio Estrella: With those governments and with the different businesses, how do you decide which of the groups that you are prioritising to work with at any given point in time? You have different programmes, so what's the approach you take?

Alexandra Heumber: The main mission of RDI is to represent the voice of our community, the rare disease community. And for that, our priority is to somehow create an ecosystem, a policy ecosystem that integrates rare disease into the various policies. It can be from health to social support and human rights.

And RDI has in a way a very interesting position because we represent our members, but we work also very closely with all the different stakeholders of the rare disease ecosystem, which is minister of health, minister of social support, but also private sector, UN agency like the WHO, organisation like the World Economic Forum.

So by doing this, we engage in regular dialogue. We really ensure that we bring people together on very relevant projects or initiative that again contribute to increase the recognition of person living with rare disease across the world.

So we also make sure that we do not only engage at global level but we ensure that we give a voice to our members in regional and local level with the different stakeholders in their country.

So we play that role at global, regional local with our members and stakeholders, and at the same time we have a very transversal approach which again goes from health to social justice. And so we often have really great collaboration with some key players.

So for example, for the World Health Assembly resolution that has been adopted in May, we had the privilege to engage at an early stage with Egypt and Spain, who wanted to really play a role and as as a leader initiating that process. So RDI again had the opportunity to develop the relationship with those two countries to really bring them the evidence that they need as well to make the case on the global health policy stage.

So this is the way we we do, we present ourselves really as a resources as well for all the different stakeholders, the resources for evidence knowledge, data, but also for persons living with rare disease that often can contribute to share their life experience. And again we have many different experts in in in the science area, health economic area as well. So we we work really with that multi-stakeholder approach. This is one of our, I would say, strong objective and strength at the same time.

Robin Pomeroy: You mentioned the World Health Assembly resolution. So this must be quite a milestone for you. I think you've probably been working to raise awareness about rare diseases. That resolution probably marks a moment of kind of global awareness to some extent. Could you tell us something about the importance of the resolution, why why it matters to you and and how you manage to to push that through or help get it get pushed through.

Alexandra Heumber: So indeed for the first time the World Health Assembly recognised rare disease as a global health priority. So by adapting, adopting that resolution, they really decided to put rare disease on at a high level on the global health agenda.

But this is the result, I would say, of 10 years of strong advocacy work and again engaging with all the different stakeholders in the ecosystem to arrive to that milestone. Just to remind that actually in 2021, the United Nations already adopted a resolution for rare diseases in New York. And then this one at the WHA, the World Health Assembly, was somehow a continuity of that first recognition of rare disease into the global UN system.

The particularity of that resolution at the World Health Assembly is the fact that it required the World Health Organisation to develop a global action plan on rare diseases. And why it was important to really have that demand in that resolution is that it will enable to translate commitment, because there are a lot of commitments in that resolution that member states agree to take, but it will enable to really translate them into action at regional and local level.

Because often resolutions are full of great principles, great commitment, but it miss the translation into action. And the global action plan will provide a framework for action with clear targets, clear indicators.

And again, what would be important for RDI is to make sure that our community is consulted from the very beginning to develop the global action plan.

And again, it would be very important that it's not a top-down approach, but a bottom-up approach, because we really want that global action plan to reflect the different realities of the different regions of the world. Not everyone has the same level of development. There are some great initiatives, great solutions that works for rare diseases in certain regions of the world.

We would like again to assess if it's something that we can scale up, that the global action plan can really, you know, take as a certain example for the country to duplicate, but always with in mind the necessity to tailor to regional realities.

So that global action plan will leverage what is already there. And there are some countries who have nothing, no no national plan, not even the recognition of rare disease into the their the health agenda. And what the global action plan will do is will enable them to take some feasible step to be able to arrive to a situation that provide recognition for the person living with rare disease in their country.

Anonio Estrella: To build on what you said, rare diseases is a unique category in healthcare because some people living with a specific condition may are so so infrequent in any particular country. It may be really hard to develop a plan to be at the population level when there's such small instances at an individual rare disease. But the benefit of having a national plan is that you can collectively look at all the people across the 7,000 plus rare diseases and have one approach that brings things together. What are two important elements out of this in in your your opinion that are necessary to have an actionable plan for governments? Things like data or an approach to innovation. What do you what are your thoughts?

Alexandra Heumber: You know, we we often see indeed that rare disease are kind of a small small quantity, because the the term rare often bring the fact that there's not a lot. But actually, more we are expanding diagnosis, for example, more we have the the the ability to collect the data and also have newborn screening, etc., more we realise that there are more actually persons living with a rare disease than we would have expected at the very beginning.

So by enabling the diagnosis, newborn screening, having a system that enabled to codify it as well to have the proper registers and data, more we will realise as well that there they are much more patient than we think that they would be initially. So it helps the recognition as well.

We have many persons living with rare disease that come to us and say, My disease is not being recognised in my country. If the disease is not recognised in the country, they're not enroled in the health system. So they're not counted, they're not visible, they're not counted, they don't have care.

So you see it has two impacts. It has an impact on on the system itself of the country, which then miss a full a lot of persons that are not in their health system. And personally, it really excludes many different family or or patients to have a proper access to to care. They're isolated, they don't know what they have, the diagnosis of disease, it's one of the most difficult things to to to to go through when you're a family and you have one of your child, you know there is something wrong, but there is no diagnostic, so you you you not refer to any services, you're on your own.

And often it's it's very detrimental because we know that if there is certain disease that are being treated at a very early stage, they they can have a better quality life. And more we wait and more it can be totally detrimental for the for the pers for the life of the person, even though they can have access later to a treatment. So actually being able to identify the patient at a very early stage, it's it's probably the most important thing. And we can do it if the country has a system to collect the data.

Anonio Estrella: I'm hearing two benefits of the action plan is that at the individual and the person living and the family caring for someone with rare diseases, there's many benefits for them being in introduced and included in the health system. But then more broadly, there's also a benefit to say expanding newborn screening across greater parts of a population, which could have other benefits outside of rare diseases as well. Is that right?

Alexandra Heumber: We exactly. I mean if if there is a plan for newborn screening - it's about capacity as well. We have to think sometimes are countries that really do not have the capacity to have a newborn screening programme, even though we we know it's the way to go, so we have to really also adapt our expectation with certain countries. But if we have a good newborn screening programme, it sometimes screens rare disease, but it can also screen all all other type of disease.

And so we often say actually that by fixing the rare disease in the health system, you actually fix the health system itself. Well you strengthen the health system. And I think this is probably perhaps why we work with WHO and and governments to in favour of having a transversal approach as well of health system strengthening, you know, avoiding walking just in silo like rare disease on one side and CDs on the other, etcetera We know that if they are there are transversal aspects, if we strengthen those ones, it will benefit rare disease will benefit other. But the other interesting thing for rare disease is that it's so complex sometimes to understand that if there is the expertise and if the health system tackle them, they it they can really fix many other aspects of other diseases.

Robin Pomeroy: You mentioned so there are other categories of disease that health systems will be dealing with. I think you said NDCs, non communicable diseases, things like cancer and heart disease. I wonder in a position you're in like that, do you find yourself in competition with those other you know, there'll be other non governmental organisations like yourself dealing in those areas. Do you find yourself in competition for government dollars or is the future actually more of a partnership?

Alexandra Heumber: That's a very interesting question. Thank you for that. So I'm going to I'm going to start by explaining what what is the situation and what ideally we we we could hear it could be. So the the situation is, for example, I was in a conference two days ago in Paris, and then I show a graphic showing that the number of rare disease, for example, it's almost higher than the diabetic prevalence, and then HIV is even lower. So we are really in the middle. And and I've been told, oh wow, I I've never realised that rare disease was almost higher than the diabetic one. So this this is a fact. This is the the fact that indeed we are as much as important than the other disease.

And there is another thing with cancer, for example. I've been told actually that rare disease is very similar to the cancer situation because the cancer is many, many different cancer that require actually precision medicine, etc. So we have a lot of parallel between the cancer and the rare disease actually.

So this is somehow the situation, and it's true that rare disease in the global health policy it's not considered as a non-communicable disease. And you could say, well, it's strange because it's a chronic, most of rare diseases are chronic disease, like non-communicable disease. The thing is that the policy in place for NCDs are totally somehow different than the one for rare disease. Because for NCDs, the focus is a lot on prevention. For rare disease, it's really not where we have to focus the effort because most of them are genetic so not preventable.

But I would say again to link with what I was saying just earlier. In fact, again, we shouldn't create competition and we should not somehow work in silo because if you look at from a health system perspective, if I'm a minister of health, if I strengthen my health system, it will benefit cancer patients, cardiovascular patients, and it could benefit also rare disease patients if I decide, if I have the political will and the budget, to integrate rare disease into my priority in the health system.

On the other hand, there are some specificities for rare disease that require really much more sometimes infrastructure, health workforce being really trained to inject some therapy. So there are still some specificities for rare diseases. But from a health system point of view, I think we can have a more transversal inside instead of a silo approach. So I would not compete.

Anonio Estrella: When you look at the starting point of what is needed across different geographies, you mentioned Spain and Egypt as major contributors to the resolution. I know you mentioned Malaysia as well to me in the past. What do you feel that low and middle income countries need to focus on as a first step? And I I love the way you've described how rare disease is a is a way to break down silos. But when you speak to ministers of health from these low and middle income countries, what's the guidance you give to them as to with the what's what's needed to create a meaningful first step in that action plan?

Alexandra Heumber: The first step is to recognise rare disease being a priority for health. Because m some countries do not even recognise rare disease, no, as a priority. So it's about prioritisation and having an allocation of a budget. We know that if there is no that finance possibility, then they they cannot integrate rare disease patients into the health system. So this this is the first thing.

And then the second is often having a national plan or a policy or strategy. Malaysia just adopted his first national policy on rare diseases. Some other country like France is the the fourth national plan now, so they have 20 years of experience, but it has really demonstrated that having a national plan enabled to really improve coordination, put put some measures that really contribute to improving the life of person living with rare disease, and it starts often by coding registers, collecting the data, and then providing the the the infrastructure for diagnosis and then obviously the the the treatment so we follow the the the patient care pathway somehow.

But again it it it's not things that have b can be done All in one go. We do not expect that from any any country. So I would say that starting again by identifying few prioritisation measures that they can take in partnership.

I would say that I have seen many low and middle income countries that really rely on the private sector to create partnerships that enable them, for example, to set up some registries to increase newborn screening.

The example of Egypt is a great successful example. They really first they work a lot on UHC, on universal health coverage, but they have also understood that to put these measures in place for rare diseases, they have to work in partnership. So this this is indeed happening.

And again, I would say that we the community, the rare disease community is the one that really has a lot of capacity, a lot of data, and create the change. We saw in many countries that it doesn't often come from the ministry of health, actually. Obviously, we need at one point the ministry of health to to put in place some policies, but the change often has come from the community demonstrating that, for example, that solution is possible, needed they they put in place some some amazing initiative in different countries.

So and this is probably the particularity of the rare disease is that that that area is led by patient organisation a lot. You have other for example, neurological disorder. The the the the health practition the health professionals are really the one that the neurologists often lead the change and path. But in in the rare disease community we we really see that it comes from the community and with a huge collaboration with all the different stakeholders, with with with with health practitioners as well. So this this is a a strong for me particularity and strength of of our of our community to create the change.

Robin Pomeroy: And what about collaboration also across borders? Because as you've already said, some countries are are way ahead of others in this, and partly that will be due to, you know, the the the advancement of their health services, but also a lot of it is about the political will that decided to take up this cause. Presumably some countries can learn from others and maybe can collaborate with others also on treatments and research and policy. Is that something that's helpful?

Alexandra Heumber: Exactly. And this is this is something that is happening actually. And I I think with the resolution of the World Health Assembly and the Global Action Plan, it will even increase that cross-collaboration.

It's because of the simple fact that because some on certain rare disease we can be very few in in certain countries, you have to look beyond. So we see a lot of collaboration at regional level, and RDI has actually a project now where we are pairing some hospital or centre of excellence on rare disease to exchange knowledge and expertise to try to sort it out some complex cases to diagnose and to also provide a clinical advice. And so we we we we are for example in the region of the east we are putting we have Singapore, Pakistan, Australia, Malaysia that are coming together and really works on on a very concrete cases and we are at the proof of concept level and we hope that we'll be able to scale up that project which call which is called Global Network for Rare Diseases.

And it's all based on the fact that rare disease and the knowledge of rare disease goes beyond just a country. So yeah, this is and and we in genomic as well. There is a international genomic project that is quite really so something. So there there are many, many different projects, regional and international.

Anonio Estrella: So you've been a major contributor to the white paper that the World Economic Forum has been putting together on rare diseases. In c in companion with in companionship with the WHA resolution and the action plan, what do you hope that can be achieved with better collaboration and coordination from the private sector with the broader stakeholders that you work with?

Alexandra Heumber: So the this initiative led by the World Economic Forum and partners to to do a white paper on identifying the barriers to collect data, it's it's a really brilliant initiative because it starts from the fact that we all agree that to make the case to invest in rare disease, we all agree that basically we need to invest in rare disease because it would create a return on investment. It started from there.

The problem is that to demonstrate that we always were facing the challenge of collecting the data in low and middle income countries, notably to to demonstrate our cases. And RDI also were involved in a project like this where we we were really facing that that challenge.

And when I realised that this white paper was going to tackle that very specific issue on how to overcome those barriers to collect data, I thought indeed at least we have something that really going to help every stakeholders, including policymakers, to again have more data, so have at least a minimum data set that would help to to make the case to to invest in rare disease, but also to encourage the best practise or the lesson learned how to also establish registries because it it goes together.

If we cannot identify the patient, we cannot n count them so we cannot get the data, even the economic data.

So I hope that from that white paper and from the conclusion that will come with it, we will be able to help also some policymakers in in different countries to start putting in place a proper system that help them to have the minimum set of data. This would be an important milestone absolutely.

Robin Pomeroy: Alexandra Heumber of Rare Diseases International.

Tony, so the UN, the World Health Assembly, passed this resolution on rare diseases. Will it really change anything, do you think?

Anonio Estrella: These resolutions might sound like an announcement and then we don't know what happens, but they're actually very crucial towards being able to drive action in three broad areas.

The first is by having this resolution, it now has the ability for governments to be able to align their resources and policy discussions around this topic. A call to action to say that a national agenda for a government in any type of country, whether we're talking about Spain or Malaysia or Egypt, now has the ability to say, well, there's a resolution, what policy change do we want to create?

The second action that this creates is it allows governments to then engage with the private sector who now have the transparency and visibility to say we focus as a private sector institution on rare diseases. We now know that there's this call to action from the World Health Assembly. How can we collaborate? How can academic institutions collaborate to create an action plan?

And then the third and probably the most visible and meaningful way if you're a family dealing with rare diseases is that there's now an opportunity for these national programmes to lead to better impact at the community level. And so there's a downstream effect of having this global resolution that ultimately lead to some level of community impact for families.

Robin Pomeroy: Let's move on to our third and final interview. You mentioned the private sector there. Tell us about our next interview.

Anonio Estrella: So Soraya Bekkali is a senior vice president at Alexion AstraZeneca Rare Disease, and she's also the head of International. And so we've been working with Alexion AstraZenica Rare Disease throughout the formation of this rare disease community, because they're one of the companies who, among many others, are able to translate the ambition and aspiration to improve people's lives and balance that out between also being a business focused on growing their pipeline and building out products that help people across different condition areas, including rare diseases.

So let's hear from Soraya and what they're working on.

Soraya Bekkali: So my name is Soraya Bekkali. I'm with Alexion AstraZeneca Rare Disease and I'm in charge of the UCan and International business, which means all what we do across more than seventy countries across five continents serving patients with rare disease where they are.

We are a company dedicated and committed to develop innovative therapies for rare disease and to make it available to patients wherever they are. We started in a few countries at the beginning and when we have expanded to now 70 countries where patients across the world can receive and benefit from those innovative therapies that we have developed.

More importantly, we are part of this journey in make putting the rare disease on the global agenda and making sure the healthcare system make provision for those patients who are today invisible in their own healthcare system.

So we are partners and we are committed partners to patient groups, patient associations, to physicians, to policymakers and payers to create collectively that ecosystem, that ecosystem that we hope to be favourable for those rare disease patients who today we know represent collectively more than 300 million globally, even if individually we are talking about a few patients here and there for each disease.

Anonio Estrella: Now this white paper that we have been working on together, the title of this paper is Making Rare Diseases Count and how better data can unlock a multi trillion dollar opportunity. Let's break that down into, first start with data. Why is data so needed in the world of rare disease research?

Soraya Bekkali: I think this is an important angle, and I really commend the white paper authors for really focusing on that because data documents the unmet need that is to be addressed for rare disease.

The data measures the impact of any intervention for those patients. And the data drives investment or guides investment, and finally it enables progress.

So this is, I would say, the foundation for any major progress and improvements for the lives of rare disease patients, because by defining the minimum data set required for every country, every healthcare system to collect, that's what will help us to put that data together to be able to compare countries with each other and to compare progress being made over time, and do that in a way that will also support innovation and progress for those rare disease patients.

Robin Pomeroy: That that goes to what you said right at the beginning that rare diseases is hundreds of millions of people affected, but very very small numbers per disease. So I suppose if you're collating data like that on a on a global basis, that gives you something to go on in terms of what the problem is, and then if there are treatments available, what's working. Is that the main difference, would you say, from a from a drug company's point of view on working on any other kind of disease and a rare disease, is that sometimes it's hard to know what the situation is globally for a lot of these diseases.

Soraya Bekkali: I think you are making a good point because for many diseases, when we look at epidemiological data, how many patients are out there?

We find little scarce, fragmented information in some countries, not in other. And what is being captured in those studies is the tip of the iceberg.

We know, for having been working in this field for the last three decades, that the more we dig into the field in into a particular rare disease, the more we discover there are many more patients that are out there that who are misdiagnosed or who take five years between the clinical presentation to the to to the proper diagnosis.

So data is important to be able to show the magnitude of the unmet need, to estimate the epidemiological parameters of this disease, and to be able to, of course, enable cross border collaboration and partnership.

Anonio Estrella: It's especially difficult for rare diseases because you may only have a very few number of patients in any one particular country globally. I think it's very exciting to see that data innovation can be something to trigger how more collaboration can happen across borders. Are you seeing that happen a lot today in the world of rare diseases?

Soraya Bekkali: I'm seeing this discussed a lot and it always comes back to are we having the the same data set? Are we collecting the same information? And I've I've I've seen some progress into that area as we see some countries now having an ORFA code where they define a particular disease with a certain code in the same way across different countries, and if this nomenclature is being used across many more countries, of course it will enable comparison and consolidation of data.

But in terms of the sharing of data, there's always this question we need a framework. Academic institutions, European reference networks, country physicians need a framework that will reassure them about the opportunity and the ability to share that data across borders while respecting the data privacy considerations and any other I would say legal question that can come from putting that data together.

So the framework that is being called up by this white paper is an important milestone of of foundational peace to enable that data to I would say serve its purpose.

Robin Pomeroy: How does a company like yours decide which therapies to pursue? You know, maybe you can give us an idea of how many diseases you're you're you're looking at at all and then how many eventually go into kind of research and development and eventually production. What the process of deciding yes, maybe we should go down this alley and not yet go down this alley?

Soraya Bekkali: So when we look at the number of rare diseases that are identified today, we are talking about 10,000. And out of those 10,000 different rare diseases, most of them being of genetic origin, which means driven by a genetic mutation or defect, only 5% of them have a treatment available.

So this leaves 9,900 and more diseases to be tackled for research and development.

And this is not of course something that we can do on our own and that's why this is being addressed by the academic institutions that try first of all to understand the pathology of this disease. What is the the biology behind a disease, what explains why this disease appears, is it genetically driven, is it acquired? So all this basic knowledge, scientific knowledge is important and comes mostly from the academic institutions across the world.

And then for for us, it's about partnering with some of these scientific communities and academic institutions around an area where we feel, from that biology understanding, we identify a potential mechanism of action that could be targeted and could lead to a treatment benefit. And that's where we contribute through our drug development I would say effort.

Us among many other industry partners in in in the world because obviously the the size of the task is is huge and we tend to I would say focus on the areas where we have an expertise, where we have developed an expertise over time.

We have been pioneers in the immune system biology and the complement system biology for the last 30 years. So clearly this is an area on which we build.

We've been expanding now beyond that into new areas where we have developed as well expertise and that's what will drive I would say an impact and our progress is focusing on the areas where we have that expertise and know-how that will enable us to develop that treatment or that innovative solutions effectively, knowing that the probability of success for drugs in development in the rare disease space is is not very high. So we put the I would say the chances on on our side by focusing on the areas that we have full expertise on.

Robin Pomeroy: And are there success stories that that you can look back on? You say the company has decades of experience in this field. Have there been breakthroughs and it's like yes we did it.

Soraya Bekkali: Yes, there have been I think this has been one of the foundations of our organisation, Alexion. That expertise in the immune system and the complement system biology has led to the development of a targeted treatment that target the diseases that are all complement mediated, which means the diseases that are resulting from a complement system dysregulation.

And if I give the example of one of those diseases called paroxysmal nocturnal hemoglobinuria, naturally, before the development of of our treatments, the the patients would be diagnosed in their 30s, 40s, and that they would have 10 years of life expectancy. And that was the natural progression of that disease in the absence of treatment due to this hyperactivation of the complement system. With the innovation that Alexon has developed, and that's 20 years ago, now those patients have a normal life, they get this treatment and they control, they inhibit completely their complement system, which enables them to have a normal life. And now those patients who used to die in their forties and fifties at max now can become grandparents, can retire, can see their grandchildren. So clearly this is an innovation that have transformed dramatically significantly for the best the life of those patients, but not only them. The family and caregivers of patients living with rare disease are as well impacted by those rare diseases. So that's why when we think about the impacts of everything we do for rare disease, it's not just for the patient themselves, but for the additional hundred of million of patient of family members and caregivers who also suffer from that situation.

Anonio Estrella: You've mentioned two recommendations from the white paper: minimum data set and building trust to be able to cross borders. If you look five years out, ten years out, and we've solved these problems through the collective will of different stakeholders, public and private, how do you see the world being different for patients living with rare diseases and the in the incremental benefits of innovation to other disease areas?

Soraya Bekkali: I think if this of all the recommendations of the white paper were to be implemented, instead of having only 5% of those 10,000 rare disease having a treatment today, after 20 years or 30 years of having major European and countries and US and Japan and major I would say developed countries having developed a framework, a regulatory framework to encourage innovation in this space, we would not have only five. We may have ten or fifteen or more.

It would accelerate the access to innovation because so far I think what we are missing is that those patients are invisible in their own healthcare system. They are indivisible of to their government, to their Ministry of Health, because of the insufficient data and the lack of consistency in the data or structure in the data that is available that enable us to be able to compare apples to apple and to see are we talking about a big apple, a small apple or a giant apple.

The data would enable that I would say sc scale up or probably uplift that we are we are missing today.

Anonio Estrella: Taking this more broadly, which stakeholder group do you view is most crucial to bring into this journey for solving rare disease challenges that has not traditionally been part of the world that we're and how rare diseases work today?

Soraya Bekkali: Today, when we think about all the stakeholders that will make any progress possible, of course, we think about the scientists, the physicians, about the patient groups, the patient themselves as key advocate for themselves and for their relatives. We think about policymakers, ministry of health, representative, and the industry partners, of course, because it takes a village for this to move ahead.

Do I see another stakeholder beyond those that I have just mentioned? Maybe the general population in terms of raising awareness around the fact that there are out there patients who are isolated, who don't have an equitable access to care just because they were born with the disease because of the genetic lottery, the birth lottery, or because the they present with something that is not as well known as hypertension or diabetes.

So making the general population sensitive to that can help.

However, I still believe that those I have mentioned and all these multi-stakeholders are those that are needed because none of us can solve this on its own and it will require everybody's effort and contribution to understand that advancing innovation rare disease will benefit broader health of of the the the general population in every country.

There are governments that have understood that a healthy population leads to a healthy economy. There are governments that have understood that by putting all this rare disease together it represents five percent, ten percent of their population and therefore it becomes a public health problem for them. So that's where the data again here will play an important role in accelerating that collective understanding that will enable this to move ahead for the benefit of patients.

Robin Pomeroy: That was Soraya Bekkali of Alexion AstraZeneca Rare Disease.

Tony, it's been a fascinating discussion or discussions with our three guests. Also, you've been working hard on a white paper, a report that people can read. It's just come out from the World Economic Forum. Tell us about that.

Anonio Estrella: So this white paper included many of our organisations and guests that we heard from. Will Greene was the lead author. Alexandra, along with some individuals from Rare Care Centre and Genetic Alliance were co-authors working with Will Greene. And we worked very closely with Alexion AstraZeneca Rare Disease, Deloitte, Merck, and Sanofi as other co-chairs and contributors to this white paper.

The thesis behind this white paper, as I alluded to earlier, is that there's been a history of rare disease innovation leading to broader healthcare impact.

And by looking at data and data innovation and data structures as a source for innovation for rare disease today, we're able to then say that we can affect rare diseases at the national level by say having a minimum viable data set that allows us to understand rare diseases by country and then apply that across disease areas.

So that then would allow other areas of cardiovascular health of cancer to then be able to have greater uses of data to support research and development, allocation of resources, and overall improve health outcomes for people living with any type of condition.

Robin Pomeroy: People can read that on the website and read about lots of other work by the World Economic Forum on Health and Health Care.

Tony, we've done the interviews, you've done the White Paper, there's been a resolution at the global level. What's next? What do you see is the future now in rare diseases?

Anonio Estrella: Well, I've mentioned a small number of organisations that we're working with right now, and there's a broader community that helped to bring their insights into this white paper, more than 30 organisations. And what's next is to go from 30 organisations to 3,000 to 300,000, is how do we get different institutions and organisations from the public and private sector to work together?

The role of the World Economic Forum is to help create public-private partnerships that can collaborate and drive impact together. And that's one part of the puzzle. By working with the World Health Organisation, by working with other global institutions and bringing it down to the community level, we hope to see improvements in rare diseases and overall health and healthcare over the years and decades to come.

Robin Pomeroy: Tony Estrella, thanks very much for joining us on Radio Davos.

You can read that white paper, called Making Rare Diseases Count: How Better Data Can Unlock a Multitrillion-Dollar Opportunity, on our website, link in the show notes.

Thanks to Tony and to all our guests on this episode - find out more about the World Economic Forum's Centre for Health and Healthcare on the website.

And follow Radio Davos - and our sister podcast Meet the Leader - wherever you get podcasts and please leave us a rating or review.

This episode of Radio Davos was presented by me, Robin Pomeroy, and co-hosted by Tony Estrella. Editing was by Jere Johansson and studio production was by Taz Kelleher.

We will be back next week, but for now thanks to you for listening and goodbye.