The Power of Patient Organizations in Rare Disease Trials

In this episode, we'll explore the transformative power of collaboration and advocacy in the pursuit of life-altering treatments. Meike Madelung from IQVIA's EMEA Thought Leadership team takes us through a compelling case study featuring the AKU Society and its groundbreaking efforts in combating Alkaptonuria. Learn how patient organizations can help accelerate recruitment for rare disease trials.

Transcript

Michael Pierre: 0:00

Greetings, and thank you for being a part of the Society for Clinical Research sites on SCRS Talks. I'm your host today, Michael Pierre, Project Manager here at SCRS. Get ready to dive into a space where we discuss pressing clinical research industry issues, celebrate noteworthy achievements, and foster a deeper connection within the research community. This is the space to amplify voices and perspectives that shape the landscape of clinical research. Today, we have Meike Madelung, engagement manager EMEA thought leadership with IQVIA. So thanks very much for joining me today Meike. Please tell us a little bit about yourself and what you're currently doing with IQVIA and a little bit about the topic of this discussion today.

Meike Madelung: 0:45

Yes, well, thank you very much for having me. So I've been working with IQVIA for quite a while now. And for a while now also with the EMEA thought leadership team. And our role really is to uncover issues that affect the healthcare space in general that are of relevance to industry. And we certainly have recently developed a focus specifically in the areas of clinical trials and patient engagement and that's also a focus area for myself. And I have to say it's an absolutely fascinating area. I greatly enjoy working here. And this particular topic I find particularly fascinating because it's really quite outstanding. We know that in rare disease, there's a lot of unmet need, a lot of development activities. And we also know that the role of patients is increasingly at the center. But what makes this really outstanding We rarely have cases where patient organizations actually drive the development of disease altering treatments in this particular space. And that's what we're going to talk about today.

Michael Pierre: 1:43

Well, thank you for being here today and talking with me. You recently co- authored a white paper showcasing the power of working with patient organizations for ultra rare disease drug development. What makes clinical research for these conditions so challenging?

Meike Madelung: 1:58

Yes I think what makes it, primarily challenging that there are just so many of them. There are around 7, 000 to 10, 000, depending on your definition, rare and ultra rare diseases. And the vast majority of those is without treatment. So there is a lot of really high unmet need in this particular space. At the same time, there's also a lot of development activity ongoing and quite a few treatments are coming to the market. So for instance, within the EU, I think around half of all new drugs to the market were actually for orphan disease. They carry the orphan designation. On the other hand, the reality is that really the vast majority of all these development projects fail. So what we've been looking at, we regularly look at the success rates of development projects in the R& D space and the composite success rate across all phases in 2023 was around 13%. Which basically means 87 percent of development projects fail. That's up from 7. 6 percent in 2022, and it's still better than the industry average. So overall, R& D is a very, very challenging job. But what we're generally seeing is that success rates in clinical trials are dropping. And a major factor really is under recruitment. So many trials fail to meet their recruitment targets. And that, of course, means there's an impact on the results. And especially in rare disease, you have a situation that there are not that many patients around. Patients for rare and ultra rare disease are few and far between. And then if you cannot even meet your recruitment targets, you very much run the risk that the trial ends up statistically underpowered and with inconclusive results. And worst case really is that the trial fails. And that's actually something that happened in this particular area that we're looking at today. There was a trial in the U. S. which ended up well, it was unsuccessful. Simply one of the major factors was there were not enough patients on the trial. And I think that what makes this particularly difficult for rare and ultra rare disease, you're looking at very small, often widely dispersed patient populations. And of course, a lot of the time these patients are not very well. So the practical issues of participating in a trial can be extremely challenging for these people. Financial problems, logistical problems, and again, all of that is magnified in rare and ultra rare disease. And the other thing, of course, is that a lot of the time the natural history of these diseases isn't very well understood, and that can make defining the relevant study endpoints a challenge, and again, something that can also contribute to the failure of a drug. And again, that's something that actually happened in this particular case.

Michael Pierre: 4:39

So in your paper, you discussed a case study with the European based AKU Society. And what made that case study stand out?

Meike Madelung: 4:49

Well, that's the thing that's a really, really exceptional situation is that in this case, the development of a treatment was actually driven by a patient organization. And I've mentioned this before, and I think we all know that patient engagement, especially patient engagement in clinical trials and also in launch is becoming, well, almost a buzzword and become very, very relevant to actually include patients in all stages of the product lifecycle, but it's really exceptional that a patient organization actually drives development of a treatment and does so successfully. And I think that's what makes this particular case stand out. And the disease we're talking about is called AKU or Alkaptonuria, and it's an ultra rare disease that affects only around 1 in 250, 000 people, so a really rare condition. And it's caused by a deficiency in the tyrosine pathway, which leads to the accumulation of a compound called HGA, and it results in damage to joints and connective tissues. So it leads to a wide range of symptoms. It's ultimately extremely debilitating. It's a progressive disease although it is not lethal. And what had happened, there had already been a trial for a very promising molecule called nitosinone And that trial had been run in the US and it had ultimately resulted in failure and it had resulted in failure for two reasons, mainly. There were only 40 percent overall on the trial and it had a control arm and a treatment arm. So essentially you had just around 20 patients on the treatment arm plus a couple of dropouts. So you ended up with very, very few patients and that eventually led to inconclusive results. But overall, the experience of the patients participating in the trial was actually quite positive. They felt a benefit from the treatment, even though the eventual trial readout did not confirm this. And essentially what happened is that the AKU society, which is the patient organization for this particular disease based in the UK. They did not believe that this trial in the U. S. had been the last word in this particular area. And so basically they picked up the pieces and they believe that Nitosinone still held promise. And they managed to raise funds from the EU to finance the trial. And they pulled together a research consortium of, I think, 11 organizations overall. It consisted of researchers and research site, it consisted of trial sites, it consisted of patient organizations in other European countries. It consisted of a pharma sponsor who was very, very involved in this particular project. And I think the in this particular case, the interaction of the patient organization and the pharma sponsor along with all the participants was really absolutely crucial to making this happen. And of course, there were also clinical research organizations involved. And essentially they started a new series of trials starting with a phase two trial and then moving on to phase three. And ultimately what happened is they succeeded in bringing Nitisinone to the market. So they did get approval for Nitisinone for AKU in the EU and the UK. And that basically means all patients in Europe, including the UK, now have access to this life altering treatment. And that's the other thing. It's a life altering treatment. It does slow or even prevent progression of the disease. And that basically means that patients living with this disease can now lead fairly normal lives. And that, of course, is a massive deal. That's a really big deal. And I think that's quite extraordinary.

Michael Pierre: 8:16

And how can patient organizations accelerate trial recruitment and retention for these rare disease trials?

Meike Madelung: 8:24

The major factor really is patient organizations know their patients. I mean, they literally know their patients, especially in rare and ultra rare disease. They know who these people are, and they have a relationship with their patients, they have a relationship with the communities, and they have a very, very good understanding of what the needs are and what the pain points are. So you know, what would drive a patient to actually participate in a trial, and what would motivate them to stick with a trial and again, literally knowing who the patients are. Because it's one of the major factors sometimes, even finding out who might be suffering from a condition is not easy. A lot of the time, rare and ultra rare diseases are underdiagnosed. They're sometimes misdiagnosed. AKU, for instance, sometimes is misdiagnosed as arthritis because some of the symptoms are so similar. Because, of course, it's a zebra versus horse issue, isn't it? AKU is the zebra and you tend to look for the horse. So that's one of the things and that of course makes them potentially very powerful partners for clinical development. And the thing is, patients and patient organizations absolutely want drugs to be developed. They want them to come to the market. They want this project to succeed. So their intrinsic motivation is already extremely high. Now we're talking about identifying patients for trial recruitment, but the crucial thing is that patient organizations can already help with the trial design because they know what relevant endpoints might be. They also know what endpoints that are relevant to the patients might be and they also understand what practical barriers to participation might be. And a lot of the time a good trial design is the basis for a successful trial. So that's probably key talking to patient organizations very early on. There could be logistical issues, how do you handle childcare for instance? How do you handle work commitments? How do you juggle that with a trial schedule? That thing can be very, very challenging. And in this case for instance, the AKU society had already run a campaign to identify people with AKU in the UK. When they first started out, they only knew of four patients with AKU in the UK. Some of them were family members of the people who founded the AKU Society. By the end of the campaign, they had identified 60 people suffering from AKU in the UK. So, that's, essentially, a ready made patient cohort right there. And they also had contacts. They had a network of sister organizations in other European countries. These organizations know who the potential patients are. They can contact them directly. They can handle the communication and explain what the trial is intended to do, what to expect from the trial. All of that is really, really crucial. And in practical terms, this meant that in the European trials, 138 patients participated, as opposed to 40 in the trial in the U. S. And that already shows you the impact the patient organizations can have. And the other thing, of course, is that patient organizations have a trust based relationship to their patients. And I think trust in this particular instance is extremely important build the trust with the patients and the patient organizations speak the patient's language. Pharma speaks a different language. So that's, I think, is another factor that's extremely important. And of course, I've mentioned practical issues before, like logistical issues. A lot of the time patients suffering from rare diseases are really not very well at all, and travel can be very onerous, or they may rely on caregivers having to travel with them. So, think about that sort of thing. Think about funding. Practical things like patients often are on disability and therefore on very low incomes, if they have to cover costs out of pocket, how is reimbursement handled? It was a very, very practical factor in the AKU trials because a lot of the time reimbursement took a really long time and patients on very low incomes often can't handle that. And so the patient organization actually stepped in and handled that particular practical issue. So all sorts of things that can actually motivate patients to participate in a trial and to actually stay on the trial as well.

Michael Pierre: 12:28

At this point, Meike, does every rare disease have a patient organization?

Meike Madelung: 12:34

It's a very good question and I'm not sure.

Michael Pierre: 12:36

Okay.

Meike Madelung: 12:37

Especially, you know, in rare disease you also have this really wide range. You have some ultra rare disease where in extreme cases you maybe only have a couple of thousand people across the globe who are affected by it. And then you have diseases like Duchenne's for instance which actually is relatively frequent for a rare disease. And they of course have a very large, very strong patient organization. But there are a lot of organizations out there. A lot of them are very, very small organizations, just a handful of people basically running the patient organizations in the evening after work, you know, sitting on the around the kitchen table after bringing the kids to bed.

Michael Pierre: 13:11

Yeah.

Meike Madelung: 13:12

There are a lot of them around.

Michael Pierre: 13:14

Okay. And what are some recommendations that you could give for sponsors and research sites to collaborate with patient organizations?

Meike Madelung: 13:23

Yeah, I already mentioned that one of the strong points of patient advocacy groups is they have a trust based relationship with their patient communities. And in that case, not just the patients themselves, but also their caregivers, their families. And I think trust is absolutely crucial for a successful collaboration between the pharmaceutical industry and patient organizations. A relationship has to be built and that has to be based on trust. And that can be a very high barrier. And that varies in some areas, in some countries it's easier. In other areas we find that patient organizations are actually very reluctant to even talk to the pharmaceutical industry because they are very worried that there might be a conflict of interest or even just the perception of a conflict of interest and that would jeopardize their trust based relationship with their patient communities. So really it is not something that's going to happen overnight, but trust has to be built. And pharmaceutical companies have to understand the motivation of patient organizations. I mean, a patient organization is not just, you know, another supplier of expertise on the patient condition and possibly of context to patients. They have a very, very strong commitment to making life better for their communities and ideally bringing drugs to bringing treatments to the market. Whereas obviously, the pharmaceutical industry has a more commercial interest. And so that barrier is actually a very real and a very strong one. And it does take time and patience to actually build that relationship with patient organizations, seek them out and try to build that relationship. So that's the one thing. Again, the fear of a conflict of interest is very strong with many patient organizations. And the other thing is and I think that ties in with the relationship building is that really from the sponsor's side, there has to be a very strong commitment and it has to be at the very highest level of the organization. So I already mentioned that the pharmaceutical company who was involved in this particular project, Swedish Orphan, or SOBI. They were very committed to this particular project. That's interesting because I didn't even have a commercial interest at the point because Nitisinone was already about to go off patent. Nevertheless, SOBI committed to this project and they committed fully and they did build a very strong relationship with especially the AKU society and that came from the highest level of the pharmaceutical organization from the company. So that was really at senior leadership level that they committed to this and sponsored this particular project and this particular relationship. And I think that's another thing that's absolutely crucial. It does mean, of course, that also patient advocacy groups will have to rethink their stance and think about adopting a more entrepreneurial and a more pragmatic approach when it comes to developing treatments for disease because essentially that's something that the pharmaceutical industry does. It's what they do extremely well. And if you actually want to end up bringing treatments to the market, you will have to develop some form of cooperation. But yes, I think trust and respect is absolutely key to that relationship.

Michael Pierre: 16:27

Do we already see or should we expect to see rare disease drug development improving with the kind of the rise of the decentralized trial and remote services that with the internet, people taking advantage of that to conduct these kind of trials with people that are not only hard to find but they're not near each other or anything at them. They could be spread everywhere. Are we seeing improvements in this kind of drug development?

Meike Madelung: 16:53

Decentralized or hybrid formats are definitely very appropriate for rare and ultra rare disease.

Michael Pierre: 16:59

Yeah.

Meike Madelung: 16:59

So in the case of AKU, for instance the research sites across Europe, they did recruit patients from really far afield. They accrued the patients from as far afield as Jordan because there was a relationship with a treatment center in Jordan. And therefore patients from Jordan were actually included in the trial and they had to be flown to the UK. And obviously, if you can remove that travel burden, that would really help or, you know, minimize the travel burden, so that's why I'm saying hybrid trials, because sometimes people will have to come on site, but you could certainly minimize that and make life easier. And, you know, there are really practical issues like childcare. Who takes care of your children while you're traveling to the treatment center? Or, I did speak to a patient advocate the other day who did participate in a trial for another condition. And at some point he was feeling well enough to want to go back to work. And obviously it's a financial issue, but I think it's also a psychological issue to be able to go back to work. And the trial protocol wouldn't permit because he had to come to the center every week. Going back to work would have meant he could have gone back to the treatment center or to the trial center only every other week and the center was too rigid to allow for that. So these things obviously could be very well mitigated using decentralized trials.

Michael Pierre: 18:16

Yeah. Well, thanks very much for talking with me today, Meike. Before we go, please don't forget to explore more site focused resources on our website today myscrs.org. You'll find a wealth of content and publications, plus the opportunity to save your spot for upcoming webinars and SCRS summits held throughout the year. Thanks for tuning in, and we can't wait to have you all back for even more enriching content. Until next time.