Drug Safety Matters brings you the best stories from the world of pharmacovigilance. Through in-depth interviews with our guests, we cover new research and trends, and explore the most pressing issues in medicines safety today. Produced by Uppsala Monitoring Centre, the WHO Collaborating Centre for International Drug Monitoring.
The views and opinions expressed in the podcast are those of the hosts and guests respectively and, unless otherwise stated, do not represent the position of any institution to which they are affiliated.
By definition, a rare disease is one that only affects a handful of people in the world. But with more than 300 million people collectively affected by these conditions and only few approved treatments available, rare diseases constitute a major unmet medical need. Christina Ström Möller from Swedish biopharmaceutical company Sobi walks us through the scientific, commercial and human challenges of the rare disease landscape.
Tune in to find out:
What drug development, testing and distribution look like when patients are few and far apart
Why patient narratives are especially important when monitoring the safety of rare disease drugs
How patient organisations work to support rare disease patients and raise awareness of their condition
Show your support for Rare Disease Day on 28 February by sharing campaign materials online with the hashtag #RareDiseaseDay or joining one of the many events planned around the world.
Rare Disease Day is organised by EURORDIS-Rare Diseases Europe, a non-profit alliance of rare disease patient organisations from 73 countries.
A recent review of orphan drug policies found that several low- and middle-income countries had developed such policies in the last decade – although disparities between countries with different income levels still remain.
A survey conducted by EURORDIS in 2020 found that the COVID-19 pandemic exacerbated the many challenges that people living with a rare disease face.
Got a story to share? We’re always looking for new topics and interesting voices. If you have an idea or any other feedback for the show, get in touch!
The Rare Disease Daily is a message to the general public, to the patients, to healthcare professionals, to hospitals, policymakers, that we need to be in this together.
Federica Santoro
Welcome to Drug Safety Matters, a podcast by Uppsala Monitoring Center, where we explore current issues in pharmacovigilance and patient safety. Every year, on the last day of February, hundreds of patient organizations around the world celebrate Rare Disease Day. This year, they'll have to do it in a pandemic-friendly manner. But the goal of the campaign remains the same: raise awareness of rare diseases and talk about the debilitating impact they have on patients' lives. Now, you may be wondering how big of a problem rare diseases really are, if by definition they occur so rarely. And it's certainly true that each rare disease may only affect a handful of people. But taken together, these conditions affect more than 300 million people in the world, which is like the entire population of the United States. And to make matters worse, the vast majority of rare diseases have no approved treatment. My name is Federica Santoro, and my guest today is Christina Strömmüller. Christina is head of pharmacovigilance and patient safety at SOBI, a Swedish biopharmaceutical company that specializes in rare diseases. Reasoning that there would be no better time to interview a rare disease expert than around rare disease day, I recently phoned Christina at her home in Gothenburg, Sweden. What came out of it was an interesting chat on the many challenges of being rare. So why don't we start with the basics? Because I'm not sure our listeners are really familiar with rare diseases. How rare are they really? And could you give us a few examples of such conditions?
SPEAKER_01
So a rare disease is a disease that occurs in a small percentage of the population. In Europe, for a disease to be considered to be a rare disease, it occurs in less than one in 2,000 citizens. 72% of the rare disease are of genetic origin. Others can be due to infections, allergies, or other environmental factors. At SOBI, the company that I work for, Swedish Orphan Biovitrum, we work with some rare diseases. I will mention a few. We have the hemophilia, which is a bleeding disorder, a rare bleeding disorder, and tarosinemia, which is a disease where the body can't break down an enzyme. And so harmful substances gather in the body and they cause a liver disease and they cause sometimes liver cancer. Another rare disease we work with is alcoptinua, and it's also a disease where the body doesn't break down an acid, an amino acid, and then there are harmful substances that accumulate in the body and cause joint disorders. Many patients around the age of 50, about half of them already have joint replacements. They can also have like heart disease and kidney stones. Another disease that we work with that is a rare inflammatory arthritis accompanied with rash and fever and inflammation in the joints and also sometimes in the inner organs, it's called still's disease. So these are examples of some rare diseases that we work with at Swedish Orphan via Vicha.
Federica Santoro
Right, so because they are so uncommon, rare diseases pose a series of challenges, and those challenges really come in at all stages from the diagnosis to the research and drug development to the authorization of medicines and finally to making sure patients get access to the right treatments. So why don't we look at them one by one? Why don't we start actually with the research and drug development? So, first of all, treatments for rare diseases are referred to as orphan drugs. Why is that?
SPEAKER_01
That has to do with the orphan drug designation that regulatory authorities give to companies who are developing rare diseases. And that is a financial incentive that allows the companies to get tax exemptions, uh waiver fees, and also exclusivity for seven years after approval. It gives them also the possibility to get scientific advice from the regulators, specific for rare diseases. And that is a financial incentive.
Federica Santoro
So a way to motivate companies to invest in research on diseases which, by definition, because they affect very few people, I imagine marketing treatments for such a small population, for such a small group of people in the world might not be very profitable for the companies. What are the challenges to developing orphan drugs compared to a standard drug development process?
SPEAKER_01
Well, first of all, the patients are few. They are very widespread. There are limited experience positions in this uh area. There are limited clinical centers that do research and have care for these patients with these rare diseases. So these are some of the reasons and challenges why clinical development in this area is much more difficult.
Federica Santoro
And so, how do you even manage to recruit enough patients for a trial, right? I mean, generally clinical trials rely on having a big enough population to assess the efficacy of a treatment. But in in a situation where your patients are so few and as you say, scattered all over the world, how do you go about that?
SPEAKER_01
In many situations, we work with research organizations. There are, like in Europe, there has been a lot of money spent by different programs such as the FP7 and Horizon 2020. I think it's about 1.4 billion euros that have been invested in more than 200 research projects. So there is also this possibility of working with these organizations, research organizations that have the clinical expertise and that have that network. So in many cases, we are approached by these research organizations who want to use one of our drugs to develop an indication in a rare disease. And in that case, the companies usually provide the drug and also provide the regulatory support to get the drug approved. So that is a way that companies, many companies in this rare disease space, also work collaboratively with research organizations which have that expertise and the network and have the possibility of reaching patients not only in Europe but all over the world.
Federica Santoro
So let's say you manage to develop an orphan drug and you want to submit it for approval. Is that process more difficult than for let's call them conventional drugs?
SPEAKER_01
The process itself requires the collaboration often with external research organizations. So often it is a collaboration with what we call an investigator-sponsor study. It's entirely run by an external investigator, but we provide the regulator support by providing the documentation that the regulators want. So there has to be that discussions with the regulator to say what is the information they require for getting approval for this drug. Now, having said that, drug development in clinical trial in this setting is more difficult because there are few patients and they're very widespread, and sometimes you don't have a comparative drug. There's nothing to compare it to. So you have to compare it to, if available, the natural history of the disease. But other times that is not even that available. So in many cases, you only get conditional approval. So if you get a conditional approval, then you have to set up a registry for these patients and follow these patients for many years before you can get a final approval.
Federica Santoro
And just for those who don't know, how does conditional approval differ from regular approval?
SPEAKER_01
So conditional approval means that you have to continue to provide evidence to the regulators that the drug is effective and that it's safe. So you continue to provide the outputs of these registries that you have set up and you provide those on an annual basis, and then you can get your conditional approval prolonged until you have um have enough information that the drug is really safe.
Federica Santoro
Learning that a treatment is available may sound like the best news a rare disease patient could hope for. Yet some patients would tell you that the best day of their lives was when their condition was diagnosed. Because they're so rare, many physicians may never have come across rare diseases or never even heard about them. And with few or no genetic tests available to point doctors in the right direction, it can take years before a diagnosis is set. Up to thirty years, according to a survey conducted by Eurordis, an alliance of rare disease patient organizations in Europe. That limbo can be a huge source of distress for patients who often report not being taken seriously or not even believed. And while they insist and wait to find out what's wrong, they're likely to be misdiagnosed and offered inappropriate treatments. But even when a diagnosis has been reached and a treatment is available, there are challenges to consider, as you'll hear from Christina in a moment. Okay, so an orphan drug is available for a certain number of patients affected by one of these rare diseases. How expensive will that treatment be for those patients?
SPEAKER_01
I can't say exactly how expensive it will be, but uh companies who develop rare disease drugs usually work with the healthcare systems to find solutions to get uh drugs to patients. There can be donation programs, there can be special programs for these patients to get the drug so it's affordable.
Federica Santoro
And I guess the problem of making sure that patients have access to the right treatments is not only a question of pricing, of making sure they're affordable enough, but it's also of sort of physically making sure they get access to those treatments, right? Making sure that first of all patients are aware that there is a treatment for their condition, and then finally putting them in touch with the right companies, perhaps, that can provide those treatments. Can we talk a little bit about the problem of access to rare disease medicines?
SPEAKER_01
So many, many of the physicians who are experts in the field, they will have access to the networks. So even if a drug is not approved in that country, there is the possibility to use something called name patient use. And the physicians request directly to the company that they would like to have access to this medicine for their patients. So if the company then approves, I think this is a correct patient, and this is the drug that is to be provided, then we have to make sure that we can import the drug in that country, and then we instruct the physicians, prescribing physicians, to send us adverse events directly to us. Now, having said that, of course, you need to get the drug to that patient, and that patient be in a in a country far away. So there needs to be a very good supply chain that can very quickly deliver that drug just to that patient. But then as a company, we also work with national health authorities to set up access programs for these uh patients as well, which would be a more long-term solution rather than a quick fix.
Federica Santoro
And what's the situation like then in developing countries which obviously already struggle with more known diseases? What's the situation there when it comes to the recognition and then the access to treatments for these diseases?
SPEAKER_01
And as you say, having a well-functioned healthcare system is very important. It's critical for having a management of rare diseases. And that may not be available in all developing countries. I would like to say though that many developing countries are getting more aware of this disease, the rare diseases. And for example, in Singapore in 2015, there was the first rare disease Asian conference that attracted many countries in Southeast Asia. And also I recently read a publication saying that many countries in these developing regions are developing orphan drugs policies, but also they have patient advocacy groups and patient organizations. But as you say, having a policy, having a regulation does lead to progress in these areas. And having seen the European legislation that was put in place in the year 2000, that led to the fact that in 2014 more than 20 countries in Europe had orphan drugs or rare disease plans in place.
Federica Santoro
But obviously, your specialty is pharmacovigilance. You head the Global Pharmacovigilance and Patient Safety Unit, that's SOBI, and you are a QPPV, so a qualified person for pharmacovigilance. So when it comes to monitoring the safety of treatments for rare diseases, what's different compared to monitoring the safety of other medicines?
SPEAKER_01
Well, one thing that is very different is that there are fewer patients and there are less safety information available. We do rely on spontaneous reporting, and in the clinical trials, it's the clinical trial reporting. But once a drug is approved, we do rely on spontaneous reporting. It's different in that sense that we have less reports. We have to understand very well the disease and also the mechanism of action of the drug, and we have to look very carefully at the content of the safety reports we get, understanding the narrative, understanding concomitant disease, and trying to put that into the context of the patient. In many cases, we have post-authorization safety studies. So we have registries that go on sometimes up to 10 years, and the outputs of those uh reports have to be presented in our periodic safety update reports. So we we write a summary of these past studies. And then we have, in many cases, risk minimization measures that we have to put in place. And in as part of that, we also follow up the patients more carefully with questionnaires and we ask more follow-up questions.
Federica Santoro
Okay, so that's really interesting. So from what you tell me, it sounds like you do a very thorough monitoring exactly because there's only a few patients affected by these diseases, you probably want to understand very carefully how the medicines affect their life, perhaps, their quality of life, and what the benefit-risk balance really is for them. And along those lines, I was wondering: are these patients more inclined to tolerate side effects exactly because the conditions are quite serious and there might not be many treatment options available?
SPEAKER_01
Well, to a certain extent, I think that is true. However, we must always try to reduce side effects. And that's why we have, in many cases, risk minimization measures, which is usually educational material for the prescribing physician and also for the patients. And sometimes we have patient alert cards where it says instructions, detailed instructions, how to avoid side effects, specifically in this disease with this drug?
Federica Santoro
I was wondering from the patient's perspective, it must feel really lonely at times to know that you're affected by a condition that really only affects very few people in the world. So, what kind of support systems are in place around the world to make sure patients feel supported and get the answers they need, apart from getting the treatments they require?
SPEAKER_01
I think that patient organizations here do a fantastic job. There are many patient organizations in different rare diseases, and in most cases, it is the patients or the carers, if they are children, that sit on the governing bodies of these non-for-profit organizations. I think they they gather the patients in their community and they provide support and the network that is really needed for these patients.
Federica Santoro
Living with a rare disease is difficult enough in ordinary times. In an extraordinary situation like the COVID-19 pandemic, it's even tougher. A survey conducted by Eurordis in 2020, as the pandemic's first wave swept through Europe, showed that rare disease patients were not coping too well. Access to the care and treatments they relied on had been severely disrupted, and many reported feeling increasingly stressed and anxious in their daily lives. Surveys like this are just one example of how ERORDIS, the European Alliance for Rare Disease Patients, supports its members. At a public hearing on COVID-19 vaccines held by the European Medicines Agency, Eurodis representatives asked that people living with rare diseases be among the first to benefit from the vaccines after the elderly and healthcare professionals. And in non-pandemic times, Eurordis keeps busy by organizing awareness-raising campaigns like Rare Disease Day and mediating the dialogue between patients on one side and people like Christina, who develop treatments, on the other side. That dialogue is one of the things Christina finds most rewarding in her job. What got you interested in the rare disease landscape?
SPEAKER_01
I had been in big pharma for many years, and then I started to get more interested in rare disease, and of course, then I got this opportunity to work at Solby. And it's been really exciting and new challenges because it is different. Rare disease is different. And it is it is very motivating because of this unmet need for the patients. So it just gives that the extra motivation to work with these patients. And it also has given me the opportunity to meet these patients. We meet the patients, we meet the patient organizations, we meet the key opinion leaders in this rare disease space. So it's very, very interesting.
Federica Santoro
Is there one say encounter with a patient that you particularly remember?
SPEAKER_01
It's not so much the encounter with the patient, it's more the parents because they are the ones who talk for their children, because 72% are genetic diseases. But I have met some very engaged parents talking about the disease, telling me about the disease, telling what they do. But it is through the patient organizations that we get to talk to these patients and to these uh carers. And the the big challenges it is for these families to have these children, but also how they share with us how what they do to relieve their pain or their breathing disorders. And uh but some of them can be sort of a bit tough, and they can say to the industry, What are you doing? You're not doing enough with my kids. And I like that because they want to have us accountable, they want us to keep us accountable. You have to do something. So it is a very different way of interacting with our patients.
Federica Santoro
But that I can imagine from your perspective, that must be difficult to hear, to receive that kind of feedback, but also extremely motivating, right? And then it gives you a chance to understand exactly what the what the patients or their carers need, really, and perhaps adapt your strategies as a consequence. So I was wondering, is SOBI going to participate in Rare Disease Day? Are the any are there any special initiatives that the company is planning? And what do you think in general about awareness-raising days like these?
SPEAKER_01
Yes, SOBI will participate in this uh rare disease event day, and then several initiatives ongoing within SOBI. I think it is a very important initiative. I think it is it is a message to the general public, to the patients, to healthcare professionals, to hospitals, policymakers, that we need to be in this together. And um, here I would also like to say, actually cite the WHO Director General who says that let no one be left behind, including people who suffer from rare disease. Just because a disease affects a small number of people, it does not make it irrelevant or less important than diseases that affect millions. So I think that is very important.
Federica Santoro
And that's a great way to end. Thank you very much for joining us on Drug Safety Matters. It was a pleasure. Thank you for listening to me and giving me this opportunity to share my experience in this space. That's all for now, but we'll be back soon with more conversations on medicine safety. If you'd like to know more about rare diseases, check out the episode show notes for useful links. If you'd like to support RareDisease Day on Sunday, visit raredezeday.org and download campaign materials to share in your channels. You can also follow the conversation online with the hashtag rare disease day. If you like drug safety matters, subscribe to it in your favorite podcast player so you won't miss an episode. And while you're there, we'd love it if you could leave us a review so other listeners can find us. Apart from these in-depth conversations with experts, we also host a series called Uppsala Reports Long Reads, a selection of audio stories from UMCs from a co-vigilance magazine. So do check that out too. Any comments or suggestions for the show are welcome. Look for Uppsala Monitoring Center on Facebook, LinkedIn, or Twitter, and come talk to us there. For drug safety matters, I'm Federica Santoro. I'd like to thank Christina Strommoll for the interview, Matthew Barwick for post-production support, and you for listening. Till next time.
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