IQVIA Holdings Inc. (IQV) Earnings Call Transcript & Summary

Welcome to today's webinar on Pathways to Overcome Challenges to CAR T-cell Therapy Health System Readiness. I'm Todd Culpepper with the IQVIA Institute, and we're very pleased to have you join us today. Before we begin the conversation, I'd like to just quickly touch on a few housekeeping items that you see on your screen now. [Operator Instructions] We do have the report on CAR-T produced by the IQVIA Institute in the Resource Box for you today. So please find and download that at any point. And finally, you will be able to view this webinar on demand about 2 hours after the conclusion of the live session. And you would simply use the same link that you used to register. So please feel free to do that and to share. And with that, I'll hand it over to Murray Aitken, Executive Director of the IQVIA Institute for Human Data Science.

Great. Thank you, Todd, and welcome, everyone, to today's webinar. We're delighted you can join us for the next 90 minutes and to hear from our panel of distinguished experts. CAR T-cell therapies have shown significant efficacy in several hematological conditions, and they do hold the potential for transformative benefits in other difficult-to-treat diseases, including solid tumors. But we all know that delivering these therapies to patients involves a complicated journey for the patient. And the associated operational and capacity needs from the health care system are also different, they're significant, and they can be costly. The first CAR T-cell therapies were launched globally in -- for the first time in 2017, which is now, some 8 years ago, but we know that the issues around barriers to access for patients remain. And we'll be talking today about the barriers, the progress that is being made and what more needs to be done looking forward. This discussion builds on a report that was published by the IQVIA Institute last month, achieving CAR T-cell Therapy Health System Readiness. It's in the public domain. We invite you to access that report and read it. The research for that report was funded by Gilead and Kite, which had the opportunity to review the findings, but had no editorial control over the final content. And funding for today's webinar was also provided by Gilead and Kite. However, the webinar has been organized independently by the IQVIA Institute. So with that, let me introduce our speakers today, and we are very grateful for them agreeing to participate today and share their perspectives with the audience. I'll ask each of them to briefly introduce themselves, and then we will continue from there. So with that, let me ask Natacha to join us and introduce herself. Natacha?

Yes. Thank you. My name is Natacha Bolanos. I'm the Head of Membership and Alliances of Lymphoma Coalition. Lymphoma was one of the -- well, was the first indication approved. So we have been working in this space since the very beginning of the approvals. In addition, I'm the Chair of the EBMT Patient Advocacy Committee. And as you may know, EBMT has the mandate to collect the data and become the registry for CAR T-cell therapy.

Great. Thanks, and welcome. Look forward to hearing more from you. Dr. Chabannon, welcome to you.

Thank you for the introduction. So my name is Christian Chabannon. I'm a French physician, Board-certified in hematology, based in Marseille, Southeastern part of France, working at the comprehensive cancer center there. I have a long interest in the development and validation of hematopoietic cell transplant and more recently, CAR T-cells and other immune effector cells. And similar to Natacha, I've been an active member of EBMT and several other professional associations, trying to promote access to CAR T-cell therapy, which remain a critical question on the topic of our debate today. Thank you.

Great. Thank you, Christian. Welcome. And finally Carmen. Welcome, Carmen.

Hello, everyone. Thank you for inviting me today for this wonderful discussion. I'm Carmen Sanges, and I am the appointed European Initiative Scientific Project Lead for the Cellular Immunotherapy Program at Universitatsklinikum Wurzburg. And I'm part of the Coordinators team for the T2EVOLVE project. Maybe we will have the time to dip in the project scope and how this is contextualized in the larger discussion today.

Great. Thanks, Carmen, and definitely, we'll be hearing more about that. So thank you, and again, very much appreciate each of you participating in today's discussion. A final person I want to introduce is my colleague at the IQVIA Institute, Vibhu Tewary. And I will ask Vibhu to take us through a brief presentation of some of the key research findings from our report published last month. Over to you Vibhu.

Excellent. Thank you, Murray. So I'll be covering, as Murray mentioned, some of the key research findings from our recently published report. Again, as Murray mentioned at the start, one of the challenges of CAR T therapies is the complexity of the overall journey for this therapy, both from a system perspective, as well as from a patient perspective. So I will first just give a high-level overview of this journey. It's a little simplified, but it still will give a perspective on where challenges can arise, and then I'll get into some of the more detailed findings in the report. So from a system journey perspective, for CAR-T therapies, we've divided it up into 3 categories. There's the regulatory review and approval. There is the reimbursement and funding, and then actually getting the CAR-T center onboarded and ready to deliver this treatment. So regulatory review and approval, this is when the manufacturer is conducting the clinical trials. The dossier is being submitted to the regulatory bodies, and these authorities are reviewing the submission and giving market authorization to the CAR-T therapy. Once that is completed, we get into the evaluation for reimbursement and funding phase. CAR-T therapies can be expensive. So determining that clinical value and cost effectiveness is important. Often, these pricing and funding are negotiated, and in many cases, there have been innovative contracting options that have been pursued. Along with funding for CAR-Ts, there's also a need for specific policies and tariffs that need to be set by national or health system -- additional health systems to cover the cost of the therapy itself as well as the associated care costs. And finally, once the drug is regulatory approved, it's reimbursed, it's funding. There's also need to ensure that centers are available. So this requires the development of infrastructure, the training of staff and upskilling of the entire team. Upgradation, so the -- from the relevant authorities, this can vary by different countries. And finally, once those are in place or sometimes in parallel, also entering into agreements with CAR-T monitors -- CAR-T manufacturers to ensure that these are available. So that's the system perspective. From the patient journey perspective, again, in a simplified manner, the patient journey starts with initial discussions about potentially the use of CAR-T with the initial oncologists to identify the right patients, check their willingness, make sure there's CAR-T availability and that these patients are eligible. These patients are then referred to the CAR T-cell treatment center by the referring physician. There, they may be reevaluated by the treating physician, and the case may be presented to a multidisciplinary tumor board. Once the patient is confirmed eligible for the CAR-Ts, the first step would be an apheresis sample. It's collected from the patient, sent to the manufacturer for CAR-T production. There may be a bridging therapy for this patient, followed by a washout period. And then prior to the administration of CAR-T, there can be a lymphodepleting chemotherapy as well. Finally, we get to the administration phase. So here, the appointment is scheduled for the CAR-T administration. The CAR-T is administered. The patient initially remains under close observation. And then subsequently, there's more short-term monitoring. This maybe in an inpatient setting or an outpatient setting depending on different setups. And then we finally get into the long-term monitoring periods. And here, there's 2 pieces. One is a long-term follow-up of the patient in terms of clinical care, as well as the long-term observational study, data gathering to ensure outcomes and safety over a substantial time period. So I covered all of this just to mention that this is a very complex area. There's a lot of different interactions with different physicians and health care providers, and it requires a substantial amount of coordination and staffing and capacity and so on. So given this background, it's also important to understand what is the current uptake of CAR-T class share. So we look at this for 5 countries: Germany, France, U.K., Spain and Italy. Here, what you see on this slide is the share of patients treated with CAR-Ts among drug-treated LDC, second-line CAR-T naive patients. This is for two years, 2022 and 2023. What you can see is that there is definitely an improvement across all of the countries between 2022 and 2023. However, there's quite a bit of variability across these countries. For example, France sees about 30% class utilization. This is in comparison to about 15% to 18% in Spain, U.K. and Germany. And then Italy has the lowest utilization based on our estimates at about 11% in 2023. So clearly, there's variability here and there's a need to understand what is driving some of this variability and what is driving the overall use or barriers for these CAR T-cell therapies. To do this, we defined 6 elements of health care system readiness. The first one is national or regional policy or strategy. What we mean by this is if there's any strategy or policy defined specifically for CAR-Ts or for advanced therapies that has a direct impact on CAR T-cell therapy and is that being regularly monitored. Second one is treatment centers. So are there enough accredited treatment centers? If yes, are they equitably spread out over the country? And are there any other challenges in that space? Thirdly, the identification and referral process. So are patients identified in a timely manner by the referring physician. If they are identified in a timely manner, can they be referred? Are there pathways? Or do they need to rely on personal connections? Reimbursement and funding. So is there a reimbursement for the CAR-T itself? Are there reimbursement for the additional procedure costs? Does this funding come on time? Does the approval for the funding come on time? Then we get into the actual initiation and administration. So as we saw with a number of steps here, are there enough apheresis slots? Are there enough trained staff? Is there enough capacity for the actual administration? And then short-term and long-term monitoring. Are these being done in the most efficient manner? Is the right data being collected? And so on and so forth. So these are the 6 elements that we looked at. To capture information on these, we used 3 sources. So we used our CAR T-cell monitors first within the IQVIA database, we looked at secondary research and government documents, and we also spoke with experts in each of these countries. So this table just provides an overall summary. I'll touch on some of the specific pieces here. So in terms of national policy or strategy specific to CAR-Ts or advanced therapies, what we found is that Spain has probably one of the best practices around this process. So since 2018, they've had a national policy. It's regularly assessed to check how well this is working and policy decisions are also being made based on these assessments. Germany also recently in 2024 introduced the policy strategy as well. We'll be monitoring this closely to see whether regular assessments are being undertaken with respect to that. From a treatment site perspective, there's a high number of centers in several countries, but these can sometimes be concentrated in a few regions as is the case in Italy and Spain, while some other places, it may be a little bit more spread out. From a referral process perspective, it's also interesting how it varies. So just to call out 2 examples, France have a relatively well-designed referral network. There's a clear pathway based on our assessment. While in the case of Italy and Germany, there can be challenges with the lack of standardized networks here, which can make referrals a little bit harder. Reimbursement can also be challenging for a couple of reasons. One is these funding -- even if the CAR-T is reimbursed, the funding may not be approved in a timely manner, which can lead to delays in terms of administration. Additionally, there may not be always sufficient funding for procedure costs. And finally, thinking about treatment initiation and administration, this was one of the major issues across all of the countries that some capacity concerns exist in some form, whether there's the lack of beds, lack of trained staff, lack of apheresis slots, lack of ability to efficiently structure the appointments for CAR-T. So there are issues in this space that each of the countries are either facing right now or will face down the line as more CAR-Ts become available. Just a couple of data points around some of these topics as well. So as you can see, this is meant to highlight the distance between a referring hospital and a CAR-T treatment center. So that's on the right side. And as you can see, it varies from 35 kilometers to 125 kilometers in Spain. Even in the case of U.K., even though it's 35 kilometers, we did hear that there are challenges around equitable access to these centers. And on the left side, as you can see in the case of Italy, there are several centers, but they tend to be a bit more concentrated towards the north, sometimes posing challenges for patients from Southern Italy to receive these CAR-Ts. We also asked the referring providers, what is the level of information that they have received about CAR T-cell therapy, which is what this highlights. What you can see here is the blue, the 2 shades of blue, they highlight that referring providers could use more information, either a little bit or a lot. And there's a pretty high proportion across all of the countries with some countries like Australia, Canada and France seeing a little bit higher level of information for the referring physicians. We also assessed, based on the treating physician, what the vein-to-vein is. So this is the time from the initial apheresis to the administration of the CAR-Ts. And this varies between 24 days in Canada to 36 days in Spain. So there's a bit of variability here. In the case of Spain, it is 36 days, but what you can see when we compare this with government documents, that this has been declining over time, and there has been a focus on this area. But there is still a meaningful amount of variability in this space. Finally, we also assessed the share of referred patients. So once they have been referred, do they actually receive the treatment? And what we find here is Italy has a higher percentage of about 72%, while the others range between 40% to 60%. Again, I'll highlight that while Italy has a higher percent once the patients are referred, we did see a lot of issues with the referral process in that country. And thinking about the time between the referrals, so the initial referral and when the CAR-T treatment was actually commenced, what we find is generally the time is between 1 to 2 months. So that's the 2 shades of blue here. But again, as you can see, there are some cases where 3 months or even more than 3 months pass between these two processes. We also asked the treating physicians what is the key element that prevents patients from receiving treatments. And the highest number that came up was the disease has progressed. So the patient is no longer eligible, which might again highlight some of the issues around delays in getting these treatments as the disease progresses in that time, highlighting some of the capacity concerns that we mentioned earlier. So finally, given these issues, there can be several approaches that need to be considered to overcome the readiness barriers. The first approach can be establishing standardized governance systems to coordinate care between referring and treating centers, developing plans to regularly monitor progress and timely access to CAR T-cell therapy, securing consistent and equitable funding for therapy and procedure costs, coordinating regular assessments of CAR T-cell therapy needs. And finally, evaluating alternative models, which can make the process more efficient with respect to pretreatment or post-treatment follow-up and outpatient monitoring. So those are some of the pieces that we had mentioned in our report to consider as well. With that, I'll hand it back to Murray to start the panel discussion.

Great. Thanks Vibhu, for that. And again, we do invite everyone to access the full report. We'll give you a QR code at the end of the webinar, where you can access it and review the content in detail. But with that sort of overview of the research that we undertook for that report, I'll ask our panelists to come in now and perhaps give their perspective on what you've heard from Vibhu, to what extent does that sort of correspond to your experience in terms of the assessments of readiness in different dimensions across different countries or in a sense what your key sort of takeaways from that summary are in terms of the health system readiness and the patient journey to access these therapies. I'll ask Natacha to start us off and share her thoughts on this.

Well, thanks for the wonderful presentation and for summarizing so well the challenges presented in the report. I want to reflect that behind each of these challenges, there are real people. And these systemic gaps that have been remarked aren't just inconvenience, but are life-altering for all these patients. Because when treatment delays happens, patients don't just lose time, sometimes we lose the whole effort that bring that patient to that place at that moment when we are making decisions about the next treatment. So it's an opportunity -- a missed opportunity and it's a waste also of all the efforts done before somehow. If we really want to unlock the full power of the CAR T-cell therapies, I think that we must build pathways that could be as innovative as the therapies themselves. Because one of the issues is that we are trying to accommodate these therapies that are completely other things. These are not just one more drug, one more medicine. It's a totally new pathway. So it -- there is a reminiscence of the transplant of the bone marrow transplantation, and we can take many learnings from that. But we cannot try to make much in the pathways as they are conceived today, but we need to think about new pathways that would really serve the therapy journey and the patient journey and pathways that are more inclusive, more efficient and that are focused on the real challenges that we are facing today. When we talk about potential solutions, and for instance, if we talk about the reference centers, centers that can deliver the therapy. Okay, one great solution would be let's certify more centers. But it's not only that because then, we realize that we don't have enough oncologists, hematologists, health care workers to serve more centers. So we need to really think of the little components of all the health system readiness to really -- to tackle those individually and also to acknowledge the realities for the different countries. And when it comes to reimbursement and negotiations with the payers cannot be focused on the price of manufacturing the product only, but we need to consider the whole pathway, including logistics, including everything that is taken from the health care system to deliver the therapy properly and all the time that is after delivering the therapy. So all the follow-up which we consider as part of that reimbursement scheme. And I would love to listen from my colleagues and then we continue the conversation.

Thank you for that. And I like the idea that pathways need to be as innovative as the therapies may be innovative, and we'll come back to digging into a little bit more how to make that pathway innovative and what the key elements of it will be. But let me turn to Christian to bring in your perspective as a clinician in terms of the summary of the research that you heard from Vibhu.

Yes. So what I like in this report is that among several elements, it provides a global view of the complexity CAR T-Cell therapies. And I refer you to Slide #8 actually because it nicely lists the stakeholders, if I can say so, that are involved in promoting access to CAR-T therapy. And what -- so what this slide simply and nicely -- this one, yes, this slide nicely illustrates that there are at least several categories of actors that can either favor or slow the access to CAR (sic) [ CAR-T ] therapy. Obviously, the companies that manufacture -- that develop, manufacture and market this class of medicines are very important players. And especially in the early times of CAR-T therapy, we've witnessed some limited manufacturing facilities that may have prevented some patients to get access to the treatment. A second category of actors are institutions and professionals in the health care system. Do we have the proper infrastructure, the appropriate number of trained personnel, Natacha mentioned that already, to be able to properly care for all the candidate patients? And then we have health technology assessment agencies, and in general, health care agencies. What is the system that favors access or oppositely, conversely slow down access to innovations? I'm French. I'm quite proud that actually, French patients had a rather privileged access to CAR T-cells, and this is in part due to the existence of an early access program in France that allowed patients shortly after the first marketing approvals to be treated with this innovative class of therapies. So my conclusion for this first part would be that if we want to make progress, we need to make progress altogether. If manufacturing facilities improve their capacities, but there are not enough trained hematologists and nurses at treating centers, then we remain stuck in the same situation. If efficient products are approved, but reimbursement is not settled properly with companies, then we have an issue and so on. So I think we'll go in more details in the rest of the discussion.

Great. Thank you, Christian. And indeed, we will and want to talk more about some of the programs that do seem to be effective, including things like the early access program that you had in France. Let me ask Carmen to come on and share your thoughts as well. Carmen?

Absolutely. Thank you so much. Yes, I totally agree with the fact that increasing access across Europe, it's a multifactorial -- has a multifactorial component, right, and also multi-stakeholders and key players. Now I would like to refer to what Christian said that if we want to move on with access across Europe, we really need to join forces, and this means that we need to learn from each other. And I think that this is absolutely critical, not only for the CAR-T therapy, the CAR-T technology. But in general, for taking up the innovation, any innovative treatment across Europe in the most meaningful, faster and safer way. So I would really like to highlight the fact that the stakeholders need to, in my opinion, really find new pathways, as Natacha pointed out, to work together jointly, to learn from each other and share as much as they can to move forward in a meaningful and impactful way, as I said. So we are still in a learning curve, right? We can still learn from the past and from what has been done. For example, the COVID might be a good point, right, to let you think that something innovative in the way a therapy reach the patient can happen if the -- if all the key players come together with one vision. So now we have probably the possibility to get to a portfolio of solutions, right? There is not one unique solution, but those solutions need to coexist, and the way they coexist can only happen in a meaningful way if the key stakeholders play together. And that's the main takeaway message, especially from the point of view of the T2EVOLVE project experience. Maybe I don't know, Murray, if I can already say a little bit about the T2EVOLVE experience or the project, right, just to let the people understand where I am coming from. So the T2EVOLVE project is a 5-year European project funded by the IMI [indiscernible] institutions that aimed at increasing the development in the excess of CAR and [ TCR ] therapies across Europe. When we took on the challenge, the 27 different partners that then came together, different stakeholders, different expertises, right? When we took on the challenge, we really tried to look into the problem from different angles because this is really like a big picture with different pieces that need to convert, right? So we really needed to move on the preclinical settings. We needed to optimize the patient journey. We needed to look into the regulatory framework gaps, right? And also and foremost, the lack of harmonization in processes across Europe that really hampered the possibility to compare data into -- to learn from each other. So you see it's really a complex picture that we wanted to tackle down. And I just would like to highlight the fact that this and any achievement that we've made in the past 5 years was possible only because industry, academic centers, researchers, small-medium company, patient advocacy groups, regulators came together and tried to address meaningfully and constructively the gaps. So -- and that's just to contextualize.

And does the T2EVOLVE initiative have some specific goals -- measurable goals where you can track your progress towards achieving the goals there?

Absolutely. For the project itself, we had a clear working project proposal. So meaning that throughout the 5 years, we were kind of obliged in a way to meet expectations in terms of impact, long-term impact as well through milestones and deliverables. And so this is what we have done so far, of course, but it wasn't absolutely only checking boxes on what we propose and promise, but we really have the opportunity to go beyond what we promised in the working project proposal and in our deliverables. Because then, while you have the opportunity to perform [indiscernible] and identify the real gaps, then you also move beyond, right? What you just -- what you know just now and you try really to address in a most meaningful way, also through collaboration with other initiatives. Because T2EVOLVE is not the only initiative, and this is really important to say, right? Across Europe, we have multiple initiatives that are looking deeper into different angles of the increasing access of the CAR-T therapies, right, or innovation in general. And so collaboration through these initiatives, it's pivotal, it's fundamental, really to create the basis for long-lasting sustainability of what we are achieving and they are achieving as well, right? So I think it's also worth mentioning that given the outcomes of the T2EVOLVE, like position papers, white papers, also continuous dialogue with regulators and different societies, we will transition in an association later on in the future, but we can talk about that later.

Okay. Great. Thanks. Great. So let's dig into some things a little more deeply. And actually, I wanted to maybe just begin by having Christian help sort of level set us from his perspective as a clinician treating patients with hematological cancers. Just kind of how does this treatment modality fit within the broader landscape of treatment options for patients? What types of patients are able to benefit the most from CAR T-cell therapies? But also how do you think this might evolve both in hematological cancers and to the extent you can talk about solid cancers or even other areas where this modality may be applied? Maybe just give us a sense of where things are going from that clinical perspective?

There are many questions actually in this single one that you just voiced. So let me try to find a few keywords for our audience. Well, first of all, if we look again at the global landscape, CAR T-cells are immunotherapies. And if you look at the proportion of innovative treatments that have been marketed in the most recent period. There is a growing proportion of immunotherapies, meaning harnessing the immune system to treat cancers is really a breakthrough in the treatment of this class of diseases. Obviously, we are still using conventional chemo targeted therapies, but the most recent breakthroughs were in the field of immunotherapies. Two, CAR T-cells are, at the moment, be used for a very small proportion of cancers, namely, lymphoid malignancies. So acute lymphoblastic leukemia, multiple myeloma, various subtypes of non-Hodgkin lymphoma. And why is it? This is because this group of diseases express some membrane antigens that turn out to be tumor antigens and malignant cells. And these antigens, we know how to properly manage on-target off-tumor effects, meaning the side effects that are the result of the recognition of the normal cells that express the same antigens and tumor cells, we know how to manage that. Basically, when we use CAR T-cells for this group of disease, we also destroy or severely damage the B-cells that make antibodies, and we can substitute patients with immunoglobulins as an example. And this is one of the very reasons why, for example, we don't have any approved CAR-T cells for myeloid malignancies, acute myeloid leukemia, myelodysplastic syndromes because there, we also have identified some tumor antigens, but those tumor antigens are also expressed in normal stem cells, meaning we would destroy the entire hematopoietic system. And that means you have to combine CAR T-cells with allogeneic transplantation as an example, making the procedure even more complex. So this is very encouraging, of course, but everybody would like to see the same encouraging results for other groups of diseases, including solid tumors. Solid tumors, different issue. We don't have such good tumor antigens identified. We have to deal with an immune suppressive microenvironment. So many things are in development, but nothing has reached the market and made commercial success so far, but we are still hoping that it will come in the future and other types of cellular therapies such as, let's say, tumor-infiltrating lymphocytes are nowadays coming to the market and raising hopes for the patient. Maybe to make it complete, the most striking progress have been made in a totally different field recently, which is the field of autoimmune diseases. There, patients have dysfunctional B-cells. So not tumor B-cells, but dysfunctional T-cells. But these dysfunctional T-cells, they bear the same CD19 antigen that is recognized by CAR T-cells that are being used to treat lymphoid malignancies. And there has been a small number, but a growing number of reports -- recent reports that demonstrate spectacular efficacy in the field of autoimmune diseases. So many companies and many academic groups are now investing resource to explore the usefulness of CAR T-cells in the field of autoimmune diseases. And just to conclude on this part of my intervention, then this raises a critical question. We pretty much included CAR T-cell therapy on top of all other duties and all other type of treatments by using infrastructure that had been developed for stem cell transplantation -- hematopoietic stem cell transplantation. We are -- we, as hospitals and as a community of health care professionals, I believe we are not ready. We are not geared up to face a growing number of patients coming from several different medical fields. And this is the next -- one of the next pressing challenges to us. So how do we increase the numbers, the capacities of, an example, collection facilities as far as these facilities to match the needs of a growing and more diverse patient population? And maybe last remark. We are making progress in the field of CAR T-cell therapies, for sure. But at the same time, progress are also being made in other fields. As an example, since the first CAR-T cells approval, we have several bispecific antibodies that have been brought to the market. Again, many indications in the field of lymphoid malignancies. And these two categories of treatment, to some extent, are competing. Because they are targeting the same tumor antigens, they are targeting the same patient population, but access is very different. In one case, we have an off-the-shelf product pretty much available at every hospital. In the other case, CAR T-cells, we have a restricted number of hospitals that have the organization in place to give access to CAR T-cells. So that creates some tension in the medical community. And how do we build a proper algorithm such that patients get the right treatment at the right time? So we are -- I would say we are living in a very complex world -- increasingly complex world. The good point is that there are many more options for patients. The bad point is that we need more resource to offer the access to those different treatments and more complexity again in designing appropriate strategies.

Yes. Thank you, Christian, very much for that commentary both helping us all understand the underlying sort of clinical aspects of this modality, but also how you ended in terms of the complexity that this represents not only for health systems, but indeed, for patients. And maybe I'll ask Natacha to comment on, again, from a patient with cancer perspective, right, how do we best help them be informed to help them be engaged in decisions about treatment pathways. As Christian points out, there's certainly CAR T-cell therapies where we're focusing the discussion today, but that is in the context that there's other treatment modalities that are out there. And I think, Christian, you also did a great job of helping us appreciate just how dynamic this space is. We really -- every day, there's some new news coming out that even the experts such as yourselves, I'm sure, struggle to keep upward and keep on top of. But Natacha, from a patient perspective, how does this play out? And what support -- what different types of support or additional support do you think patients need to help them navigate through this journey with their families, with their caregivers? Your thoughts would be appreciated.

Yes. Thanks for the question. And also thanks, Christian, for the overview, also considering what's coming next with the new diseases that are going to be approved soon. Well, more than ever, patient advocacy groups need to be an equal partner and ideally with decision power. One of the issues is that when we talk about patient engagement, it's more about tokenism. It's like a tick in the box, but it's not really working. It's not working well, simple. In -- first, because the inputs are not incorporated early, as it should. And the issue we've incorporated early the patient input is to really understand what are the challenges from the patient perspective and what are going to be the key factors that could impact the decision of the patients to go through the therapy or not? And also, what are the information needs? Patient advocacy groups feel -- have a position that it's ideal not only to provide good information, timely information, accurate information to patients based on real world data, based on clinical trials and based on the indications approved, but also help patients and their care partners to navigate the health care system. Our health care systems are very complicated to navigate. And in a pathway as the one we have for the CAR-T, which is not ideal, it's even more complex from referrals to the logistics. And so sometimes, it's not really fair that at the end, what is deciding that patients are going to be offered for this therapy or not is because the clinicians are -- have a clear -- a natural relationship with the centers that deliver the therapy or because it's in their top of mind. They have had experience, they have had the opportunity to get good training. As I mentioned at the beginning of our conversation today, when we talk about paying for the therapy, we are not really discussing the investments in the health care system. And we are investing less and less in the health care system. And that -- we cannot afford that anymore. It's time to really invest in the system, because the system, otherwise, will collapse. And the reality is that -- Christian already mentioned that for CAR-T, we are adopting all the infrastructures that were built for hematology. The patient advocacy groups that are working in this space are also naturally engaged and connected with these systems and with the health care professionals and with the scientific societies working in this space, but without decision power. And we are more involved now in the policy through different projects, but I want also to call the attention to the way even funding from European Commission works. Carmen mentioned before, T2EVOLVE has been raised to bring together all stakeholders, including the patient advocacy group that has been crucial to really bring together all the information available that can help to build capacity, to build better communications between doctors, patients and also to understand how to better support the patients, how to provide unbiased information about the risks, the potential benefit, what getting this therapy means. Because for some, may not be the easiest pathway and for some patients, the outcomes may not be those that were promised at the very beginning. And we need to be prepared for that because that's how real world works. But when we talk about projects that are trying to manage and to deal with all these challenges and proposed solutions, these projects are conceived as 5 years' projects, 5 years only. So you allocate some funding for a 5-year project, it takes much more to come to real solutions and to the implementation of those solutions. 5 years can take only to understand what are the challenges that are coming next. Because it's not the situation that we have today, we need to get prepared for what's coming next and what Christian already mentioned, the new indications coming, I can tell that in my work as Head of the EBMT Patient Advocacy Committee, we are already connecting with the patient communities that are getting clinical trials right now are not naturally engaging in the bone marrow transplantation space. The doctors are not used to be connected and to communicate with the hematologists and with the medical specialties that work in the CAR-T space, and we need to build all those connections, we need to build that network. And we don't have any investment looking into establishing that environment to support the incorporation of new patients, new indications, new needs -- new information needs, also in new support needs. Hematology cancers, at the end, are diseases you know that you get. You have some opportunity to get cured. In some of them, CAR-T has come to be adopted as potentially curative treatment. Many of these disease were conceived as chronic and degenerative diseases. So the pathway the patient brings is completely different, and we need to accommodate to those. So that's why it's so important to consider patient advocacy groups from today as equal partners to really listen. Most of the patient advocacy groups do build evidence. So they are evidence-based advocacy groups, and they have the ability to transform the patient experience into data. Data can be integrated to ensure that when we move to decisions, we are understanding all the challenges in real life. It's not only about real world evidence as we think of the registries data, but it's also real world evidence, what's going on with the patients in real life that are not matching the criteria of those super narrow criteria that are commonly designed in the clinical trial that not always represent the majority of the patients outside and the lack of information and the low literacy levels that you find out there. And I will stop now because I want to listen from my colleagues.

No, that's a lot. And I think we need to come back to when we say we need more investment, where is that investment coming from? How do we establish the need in a compelling way for that incremental investment? But let's come back to that topic now. But I want to bring Carmen in because I'm sure you have a perspective on this too from the patient view as to kind of where we are, how we need to progress again in the context that so many other things are changing in terms of treatment options, modalities, approaches and so on. What are your thoughts?

Yes, absolutely. But if I may, I also wanted to pick up on what Natacha just said because I think that this is an important paradigm shift. We're talking about the technology, right, a very specific technology that is accumulating an incredible amount of knowledge from different indications and applications. So creating the right tools and the right ecosystem for sharing knowledge, it's absolutely pivotal. And so I would like also to anticipate a little bit about the T2EVOLVE Association and why we -- after the end of the project, we think that this association might be really important in the European landscape. So in the past 5 years, we tried really hard to accommodate what our wishes and ambitions and expectations were in terms of harmonizing the processes, for example, and fill the gap of lack of the harmonization and also the collection of data. It's been an incredible effort because this harmonization is not only across Europe, but it's also mostly in the country itself. And also the way the data, as we said, is collected, is scattered, and it's not absolutely comparable even in the same country. So say that we have done what we could do in a 5 years' project like, for example, setting immunomonitoring panel that could be standardized across Europe. Like, for example, setting guidelines for raw and starting material, putting the basis for platform technology approaches applied to CAR-T and cell therapies in general. For example, we are now working on recommendation for informed consent form that are specific for CAR-T, but also implementable for other technologies. But how do we continue that? How do we sustain that and the background that we put out there? So really, at this point of time, the T2EVOLVE Association was basically the only solution. But as Natacha pointed out, it's not always true for all the projects, right? Not all the projects have the possibility to continue that. And so that's why collaborating between the different initiatives, it's important also to sustain each other because T2EVOLVE will also embrace sustainability for other projects in the future. And this is because we are basically fighting the same fight, right? And so we will really try to converge all the learnings into there. And one important point that was raised is about the data, right? So one of the biggest efforts that we have done, and this is also thanks to the collaboration with GoCART Coalition, and Chris and Natacha are very much involved in this effort. We are trying to create a core data set for the CAR-T therapy that can be -- that can have consensus across Europe. And really, this is the only way to go if we want to create the backbone for the future learning in the field.

Great. Thanks. Well, certainly, the role of data, extremely important. Harmonizing data, not straightforward. And that harmonization also, I suspect, needs to be dynamic because as we learn more, we realize maybe we want any different data. And I think to Natacha's comment, it isn't just about clinical data, it's also about patient experience data. And I suspect the more we get to work with that kind of data, the more important we realize it becomes in -- actually in linking to outcomes of the patient. I mean, this is an area we've been thinking about for quite some time. And really, the lack of the use of patient experience data linked to clinical outcomes, in fact. But certainly, that harmonization is a big task. And certainly, I applaud the efforts underway to try to make that happen across all of Europe. To the audience, thank you for those of you submitting questions. I do want to get some of them answered, and we'll turn there for a minute -- in a minute. But can we just pause for a little bit and reflect on the fact that the research that we published in the report and the focus of, I think, a lot of the discussion so far is still on those countries that have the more advanced health care systems, that have the higher health care expenditure and capacities and capabilities. But to your point, Carmen, you're talking about initiatives that are spanning all 27 EU member states. And a lot of those are not so advanced, perhaps. Can we just talk about what's going on with CAR T-cell therapies in the rest of Europe, shall we say? And what is the approach -- what is the appropriate approach, I would say, to trying to advance the awareness and use and benefit of these therapies in that part of Europe? Carmen, do you have some thoughts on that?

Absolutely. So -- and the Eastern countries at the moment are looking very much into the European landscape in the principle -- in the States that are already utilizing their own models to increase access and to provide these therapies to the patients. And of course, the thing is that they are observing and they are acquiring the most suitable model for them. In some of the Eastern countries, for example, they are applying the Spanish model. Because they have no real access at the moment to the commercialized products. They are now looking into point-of-care manufacturing and hospital exemption as well. So if this is the solution, as I said before, I mean, we might have a constellation of different solutions that need to coexist. And this is really absolutely something that we need to accept. All those stakeholders need to accept that for different environment, for different scenarios, we might need different solutions. And so we should really play smart and play together to really define what are the common fights to take on. For example, referral network. If we need to empower referral networks across Europe, this is a common value. This is a common fight that we need to take together, right? And independently, if we have a centralized -- decentralized point-of-care manufacturing, we need to inform in the consistent way, the different referral points. Outpatient treatments. If we -- if outpatient treatment is a way to go to lower the burden of the treatment centers and to really kind of split also -- yes, the burden and as I said, then we need to work together such that outpatient treatment processes are empowered and can really work in a meaningful way and in a harmonized way across Europe. And so that's why I think that really finding a neutral space like an association, like an ecosystem that is growing now to really pick and fight for those common needs, it's absolutely pivotal, because then, we move forward. And as I said, I mean, the problem with the access also for the Eastern country is that we might need to have immediate actions right now to bridge the gap. And we can look for each other to really take and extract what is now bridging the gap. But then in the future, we need to work together towards long-lasting frames or frameworks, right? So that's what I wanted to point out. And I don't know if Natacha and Christian would like to take on that?

Christian, from a clinical perspective, anything you want to add?

Yes. Yes, certainly. First of all, inequal access is not an issue that is restricted to CAR T-cells. In general, access to sophisticated therapies and expensive therapies is broadly linked to the gross income per country. Again, if I use the example of stem cell transplantation, the first clinical results were described more than 6 decades ago. And still in 2025, it's easy to document that access to stem cell transplantation is very different from one country to another, from one continent to another. In Europe, as an example, there is a sort of gradient. As you move eastwards, then you have decreased access to stem cell transplantation. And I am not a cardiologist, but I would bet that access to cardiac surgery, probably, you can document the same trends. And if we get back to hematopoietic cell transplantation and if you look at Africa, 1 billion -- there is only a handful of transplant centers over there and basically no access to CAR T-cells. So it really depends on how much money countries decide to invest in their health care system and what is definitely be of concern today, and I think Natacha stressed this already, is that priorities in this era of political turmoil may actually shift in the next few years. And that governments, for a variety of reasons, may decide to invest less in health care and more in weaponry and just having armies ready to sustain whatever conflict will happen in the near future. But money is key, and resource are key to faster access to CAR T-cells. That said, I think that even with the existing human resource, and that's what Carmen already stressed, we do have a responsibility to organize properly the training and provide the educational tools that are needed both for patients, but also for health care professionals to fully understand the potentials and the requirements of this new class of medicinal products and to understand what is truly specific to this new class of medicinal products. It's very different to prescribe CAR T-cells to a patient on a bispecific antibody. Again, because the bispecific antibody is an off-the-shelf product. Just give a call to your pharmacy, and you'll get access to the drug. If you want to treat one patient with CAR T-cells, you have to convince the referring physician to send the patient to you, you have to get organized with the manufacturing facility and the collection facility in order that everybody gets synchronized, and you have to wait for X weeks, and in the meantime, care for your patient, who is suffering of a potentially life-threatening disease. So this is something very different. We need, again, to train people. And I've seen a question in the Q&A section that in this new field of indications like autoimmune diseases, we -- the health care professionals who have no experience, no history of using cellular therapies to treat their patients, that's even more challenging because not only do we need to inform patients, but we also need to train health care professionals, I would say, and this is not negative, but from scraps because there is no prior background in this field.

Natacha, did you want to add anything? Or...

Yes, thanks for mentioning that. And I want also to refer to questions that are in the chat box referring to the need, also to understand what are the information needs and the different therapies. So first, I also -- I don't think it has been mentioned before. When it comes to determine also what therapy is going to be offered to a patient, and I know today, we are focusing on CAR T-cell therapy, but CAR-T can be an extraordinary therapy and not necessarily the best therapy for a specific patient. So we need to present -- that's why I mentioned before about providing unbiased information. It's not a therapy that we want to deliver to the patient, but the therapy that really match their preferences, life goals. And when I was referring before about the investments and thanks, Christian and Carmen, for acknowledging that. I want to stress again, I really want to call the European Commission to seeing how to provide longer multiyear milestone to allow us to move to the -- to scale the project to real life, to bring this, first, thinking of equitable delivery, scaling of infrastructure, scaling the workshop -- the workforce, and also thinking about how to provide more capacity to collect data that is not only focusing on clinical outcomes, but also allows registries to collect quality of life, determinants of health of the patients that are getting the therapies, and this is not only for CAR-T, but also for all the therapies. Those strategic investments that can secure European scientific leadership and -- for tomorrow because I want to recall also when you talk with patients about what are their concerns and they stress communication gaps with their doctors and you are trying to educate patients, how to empower them to have better conversations, more strategic conversations with their doctors. And the first thing every patient says that they don't have time because they perceive the pressures that the health care workers are suffering. And many, many times, it's because of the administrative burden. Personally, I don't want to see hematologists losing, and allow me to say that word, losing time in putting information into a system because that's administrative work, expensive to get that expertise and that knowledge, to have the fantastic health care workers we have in Europe that we shouldn't allow ourselves. We cannot have the luxury of wasting that capacity in administrative work. For that, we need a different worker. So doctors could be fully dedicated to diagnose, to treat, to communicate well with their patients and to decision on what treatment can provide the best benefit to the therapies and to that follow-up. So we need also to think of that as part of the health system redesign. It's a total -- it's considering a new way and how we can learn from each other, not to repeat the same mistakes. But instead of that, bridge between research and real world use and also build bridges for cross collaboration and for stakeholders collaboration as well, so we can really take the best. I don't want to have 200 projects working in very similar things. I prefer to have 20 well funded for much more than 5 years, 10 years, 15 years, so they can be sustainable, but they can be also bringing very concrete outcomes to the systems from all dimensions: cost-effectiveness, quality of life, clinical outcomes and health outcomes, of course. Because at the end of the day, this is about society and benefit. This is about having an investment, deciding on an investment that will secure a return to the society. And we have that possibility today to ensure those returns, but we are blocked in the bottlenecks. And I think that we are smart enough and we have the human resources and the will to really do this. But our politicians and the people who have decision power need to trust on those who have the knowledge and the expertise. Sometimes, the decision power is not necessarily in the hands of the people that have the better expertise to make those decisions. So we really need to bring all stakeholders together and listen to those who have the right knowledge to have the right expertise so we can make better decisions to ensure that those investments are going to secure more people living longer and living better.

Great. Just not to get us sidetracked on artificial intelligence. But your comments about the administrative burden, the communication with patients, the time required for perhaps what might be considered nonessential activities. I mean, there is growing evidence that large language models can actually play a useful role with ambient listening, with generating notes and tailoring communications with patients in a way that is much more effective than a clinician communicating with patients. And I do think there's a lot of opportunity that we're on the verge of realizing in terms of bringing some efficiencies through the application of AI. A long way to go, but I think that's definitely on the horizon. We have about 10 minutes left, and this has been a great discussion so far. But I wonder if I could have maybe Carmen come back and then Christian, just to reflect a little bit more about this slide that I've pulled up that Vibhu presented with some of the approaches needed to improve health system readiness. And any comments you have about the priorities among these different areas or the areas of greatest near-term opportunity? Perhaps any sort of reflection on where we go next and some of the concrete steps that can be taken around these sorts of approaches to improving health system readiness? Carmen?

Yes. I'm reading through the slide.

Yes. Yes.

Yes. Absolutely, alternative models associated with pretreatment, post-treatment, follow-up and outpatient monitoring. I mean, this is, in my opinion, on the line, where there is a common value for really trying to standardize and to bring the knowledge together and to optimize as much as we can, really to optimize the patient journey. This is really about the patient journey itself and how we can lower the burden on the treatment centers as well by empowering the outpatient treatment centers, right? So this is absolutely something that I would prioritize on a pragmatic point of view for the future, right? That it's also of a common value for all the stakeholders. And would I -- I don't see here, for example, is how to overcome, for example, specific delays like the cross-border delays when it comes to inter -- so in the same country, when you have the situation where different regions are actually accessing the treatment in a different way. And so for which some of the patients coming from less fortunate regions need to travel to regions that already have implemented the new therapy and how these cross-border agreements can actually delay the therapy accessibility. So I think that this is also something that we need to carefully take in consideration when it comes to prioritize, yes, next action items. And there are, for example, cross-border agreements, if we want to talk about again in Eastern countries, there are some Eastern countries that are also serving as treatment countries for neighbors. And basically, it develop cross-border agreements that are working beautifully, right? And so that's why, again, the dialogue and the exchange of learning and models is here pivotal while we are still in the learning curve. But this is something that I would definitely prioritize as well. And I don't know if Christian and Natacha want to also pick on that?

Christian, maybe first?

Yes. I am also a strong believer in organizing treatment courses. And you mentioned AI for helping in communication between health care professionals and patients, but also I believe we do have to identify each critical step that contributes to the vein-to-vein or brain-to-vein turnaround time that may be a huge problem for a fraction of the patients. And CAR T-cells are really paradigmatic of the need of communication and coordination between, again, different actors, some that belong to the health care institutions and others that belong to pharma and others that belong to health care agencies and regulatory bodies. This is something I have done at my own center. We have designed a software that helps us go through all the successive steps in giving access to stem cell transplantation, and I think this kind of tool will be helpful in the future. And not only will it be a tool for individual patients, but that will also help us prepare and calculate indicators that could help identify where there is tension and where there is not and the situation can evolve over time. At the moment, as an example, I'm quite concerned about the number of trained professionals that are in a position to work at critical facilities such as the collection facilities I mentioned previously in this discussion. So we definitely -- I like to say that I believe we definitely need to bring some more entrepreneurship spirit in the hospital. I think the culture in the medical world is rather in a one-to-one discussion between the physician and the patient, but this is history. This is no longer the way we need to work together. And unfortunately, we didn't have time to elaborate very much on the development of new products, but that also needs and involves collaboration between scientists and health care professionals and companies as well. So my keyword would be we need to improve our collaborations, that everyone feels happy with the step -- stage of the treatment is in charge of delivering for the benefit of patients.

Great. Very, very good, very helpful. Natacha, your thoughts?

Yes. Just to build on what Christian already mentioned, I just would remark that achieving equitable access to CAR T-cell therapy demands more than innovation. It demands cooperation, as he already mentioned, and smart niche-driven investment. So somehow, we have worked in isolation. So we have a lot of isolated efforts, but we need to move to collaborative funding frameworks that bring together all stakeholders to assess real world needs across countries and across regions as well to understand well where infrastructure is lacking, where workforce expansion is critical and where patients that's waiting for access, for information, for referrals. So we can decide those strategic investments, but those to be guided by needs assessments in real life. And I'm not talking -- I'm not only talking about funding research, manufacturing, but directly on thinking how to improve the patient experience. I love that Christian mentioned performance indicators. We need that also to evaluate the incremental advances in the patient experience. And this can be easily translated in reducing time to treatment, expanding treatment availability across countries or across regions, supporting patient navigation, supporting follow-up care, addressing quality of life outcomes, not just clinical endpoint. So there are many ways to incorporate key performance indicators that also tackle improvements in the patient experience. And I'm talking about investments where the patient journey tell us where to invest. We need to think about the therapy journey, about the health care professional's journey and the patient journey and then to understand where they interconnect. So we can understand the gaps and try to tackle those. And this means that we need to cooperate at every level to turn this life-saving science into life changing experience for every patient everywhere. And -- because it's not -- this is a scientific success at the end of the day. And we all feel lucky about having this opportunity, but we need to transform into patient-centered success, and I don't think we are yet there.

Yes, I think that's well put. We have these tremendous advances from a scientific perspective, bringing new treatment options, CAR T-cell therapies being one of them, which, again, have a long way to go in terms of their potential application in other disease areas. Meanwhile, other modalities are coming along, and we've just published our R&D trends report, which looks into the pipeline and the clinical trials, early-stage trials that are being underway, and we know there's even more innovative approaches coming along that will emerge over the next 5 to 10 years. So it's a constantly changing area. And the burden that, that does put on health care professionals, on health systems, as well as on patients to -- for each of those stakeholders to be able to realize the benefits from these advances, I think, is something that's generally underappreciated, underinvested in. And I think everyone has talked about the importance of cooperation among stakeholders, within stakeholders, within countries, across countries, right, at all levels. And the progress that we can foresee is tremendous, but we also know that getting there is going to require a lot more, not just discussion, but also investment commitment. And data always helps to be able to track our progress, as we like to say at IQVIA. So we're at the end of our time, unfortunately. We did get to cover some of the audience questions that came in, but certainly not all of them. And as a reminder, there's more questions than we have time to discuss. But perhaps we'll have further opportunities to talk through some of the areas we've focused on today. Here is the -- is where you can download the report that we've been referring to on using that QR code. We also invite people to join the IQVIA Institute mailing list. This is the way to stay informed about our latest research. We do have a big report on global trends in oncology that will be released next month, just prior to ASCO. And if you join our mailing list, you'll get an automatic notification about that. Let me close by, again, thanking our audience for your interest and participation today. But especially, thanks to Natacha, Carmen and Christian for your terrific contributions to the discussion. Thank you, Vibhu, for not only presenting the highlights of the research, but leading the team that undertook the research there. And with that, I think it's been a great 90 minutes. Thanks again to everyone, and I wish everyone a good day. Thank you.