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How shorter clinical trial processes prolong the lives of patients
In this episode, Adlai Goldberg asks Tamie Joeckel, ICON’s Cell and Gene Therapy Global Business Lead, if an increased volume of CGT clinical trials with an accelerated process leads to more life-saving approvals.
There are 2,600 cell and gene therapy clinical trials taking place this year. In the US alone, this could translate up to 20 new therapy approvals in 2022, which presents a clear opportunity to make more life-saving therapies available to a greater number of individuals.
In this podcast, Tamie Joeckel – ICON’s Cell and Gene Therapy Global Business Lead – tells us what makes an increase in the volume of trials and an acceleration of the clinical trial process significant. She explains how doing so will allow diseases such as Alzheimer’s, Parkinson’s and diabetes to receive more focus.
Within the trials, the role of a sound digital strategy is at the forefront. In cell and gene therapy trials, 80% of data comes in within the first two months, compared with an even spread over years during a traditional trial. The need for an organized and effective strategy is paramount to make critical decisions.
As the trials continue at speed, the knock-on effect also needs to be addressed. Supply chains models, manufacturing models and delivery models will need to evolve to ensure patients have access.
Despite the complexities involved, it’s a significant time in the life sciences sector. Even more so for Tamie. As a parent of a grown child with a rare disease, her mission is personal and emotive. With everything moving forward so encouragingly, she is optimistic and excited for the future.
Four things to take from the acceleration of cell and gene therapy clinical trials:
An accelerated clinical trials process means more trials are progressed, leading to an increased number making it to commercial availability.
There are challenges to overcome in regard to therapies reaching the patient – supply chain, manufacturing, delivery and, of course, cost.
The digital strategy within clinical trials must be sound. Incoming data must be organized to be fully effective.
COVID-19 led to trials becoming decentralized and for risk mitigation to be included in business continuity plans.
For your convenience, full text transcript of this podcast is also available.
Adlai Goldberg
Good day, everyone. I'm excited to kick off this next series in our podcast around cell and gene therapies, and today we have a very exciting episode to share with everyone. Data shows that in 2021, there are about 2,600 different cell and gene therapy clinical trials in different mortalities, at different stages of maturity. This is signaling the potential way of product approvals starting in 2022, and in the US alone this would translate to between 10 and 20 new therapy approvals every year, maybe even more.
As cell and gene therapies move to commercialization, what have we learned from such a robust, clinical trial process? Where are we going to see headwinds that need to be addressed, and where do we have opportunities to bring more of these lifesaving therapies to more individuals? What do we need to do? In this episode, I am so lucky to be interviewing Tamie Joeckel, ICON’s Cell and Gene Therapy Business Lead for Clinical Research Services. She spends her life, each and every day, looking and managing the clinical trial processes for cell and gene therapies, and I think has quite a wealth of experience to share across this really important topic that we're about ready to explore. But before we kick off, Tammy, welcome. I'd like to ask you a question. The first question being very important. Please let us a little bit about yourself.
Tamie Joeckel
Hi, Adlai. Thank you for having me on your podcast. This is a really exciting and great opportunity to talk about this new frontier of medicine that really is becoming much more important in the life sciences sector. I've been working for over 30 years in life sciences. I started working with some of the earliest CAR-T programs. What I did primarily was look at logistics and distribution strategies, these are living therapies, they're highly time and temperature sensitive, and so you really have to look at the supply chain very differently, and I joined ICON about two years ago. They have a very focused Center of Excellence on cell and gene therapy, and I joined them as the cell and gene therapy business lead and assist with overall strategy, and then do support of all of the programs on global logistic strategies, so, again, thanks so much for having me.
Goldberg
I'm really excited to be spending this time with you, Tamie, and looking forward to what we'll be able to share with the listeners. And I mentioned at the beginning, we're seeing a volume today which is pretty outstanding of more than 2600 different clinical trials underway. Do you believe that kind of pace and quantity will continue? Do you think it's going to go up? Do you think we're going to start seeing even more, or go down, decrease, and we're kind of in a little bit of a wave? I'm just kind of curious from a clinical trial process.
Joeckel
I think everyone is expecting that the volumes are going to increase if you even think about what the FDA has been talking about and announcing, the fact that they have to hire more reviewers because the volumes of the INDs and applications that they're getting, it becomes a little bit of a gating issue in that we've got to be able to have reviewers for these. And cell and gene therapy is one of the fastest growing markets in the life sciences sector for sure, and I think that as we move forward, we're going to be doing cell and gene therapy research in more therapeutic areas for more diseases, and I think that's really what we are seeing right now. I mean in the beginning, oncology was really the primary focus for cell and gene therapy, and it's still the main therapeutic area. I would say a good 50 to 60% of the work that we're doing is oncology cell and gene therapy.
But, we're also now seeing therapies that are targeting indications that have larger patient populations, like diabetes, cardiovascular disease, stroke, Alzheimer’s, Parkinson’s, all of these programs are now starting to come out of academia and entering the clinic, and it really stretches us, from both the clinical and the patient recruitment side, getting to key opinion leaders, training these sites who've never really worked with cryopreserved products, that the supply chain and handling of the IP certainly becomes a challenge. I think another thing that we're seeing in cell and gene therapy that's somewhat unique and exciting is we see a lot of combined phase one and two trials, we're actually talking to a sponsor right now with a phase one trial that's moving directly into phase three, and when you consider that, many of these therapies are addressing unmet needs, we're also often working under accelerated regulatory approval timelines, and so you really have to, it keeps you on your toes for sure.
Goldberg
I mean it's interesting that you've raised also about acceleration, both in terms of the clinical trial process, but also the process to commercialization. Can you spend a little bit more time around, how quickly you think we'll see these therapies and these growing numbers of clinical trials actually hitting commercial production?
Joeckel
Well, obviously we've got a large number and it's growing from an approval process. We are seeing that the clinical trial process is probably a little more abbreviated than what you normally see in a traditional because we are looking at unmet needs. I mean just look at the COVID-19 -19 vaccines, the ability to accelerate that, have that out there as compassionate use, these are the kinds of things that we're looking at especially like I said, when we're looking at research and development for diseases that are unmet needs.
Goldberg
You raised, it's a very good example, of COVID-19 and kind of the acceleration of that, and these many other therapies that are really addressing the needs of those that haven't had answers or approaches kind of in the past. And so I'm just kind of curious, if you could just kind of zoom out for a minute, cause you've been in this space for quite a long time, I would just love your thoughts around, as these cell and gene therapies really become more readily available as you've said, how do you see the therapeutic world changing? What is that going to look like?
Joeckel
From a personal optimism perspective, I just hope that, the curative nature of these therapies proves to be completely durable and we're curing diseases. But when you start looking at the actual, how is this going to impact the supply chain models, the manufacturing models, the delivery models, the things like that, I think that the two biggest areas that we're going to have to continue to evolve and change to address scaling these therapies to larger patient populations are the manufacturing and supply chains, and then also, we have to start considering on a commercialization side, the reimbursement models to ensure that patients have access to these therapies. From a manufacturing CMC Supply Chain, we certainly need standards. We are still in the midst of developing standards, and we work on that constantly. The manufacturing process for these therapies is really complex, like I said, especially for autologous. You've got an entire manufacturing clean room that's locked up to manufacture a dose of one, much better if we could move to more of an allogeneic, more of a bulk manufacturing multiple doses, but if we're still in the autologous world, we've got the manufacturing and the regulatory environment surrounding it that's really, we're tailoring it today to the complexities for cell and gene therapy, and there's a lot of work that still needs to go on to define those standards.
Manufacturers, we're seeing a lot of growth in the contract manufacturing space, I see that that's going to, probably be an area of continued growth. They're looking at constructing more flexible facilities, we can't manufacture cell and gene therapies using archaic technologies and equipment and facilities, they're really looking at trying to automate the processes and then really make evolutionary changes in manufacturing to produce a wide range of cell and gene therapies and to make it maybe a more closed and automated process so it's not so manually intensive and I think that's going to be important as we move forward and they scale. It's interesting because you start looking at the fact of being flexible and agile organizations, we talk about that all the time, just in executing the clinical trials, it really applies up and down the entire ecosystem for cell and gene therapy. We have to continue to be flexible, we have to continue to evolve, we have to continue to be agile. I think once we've solved the manufacturing problem and we have the therapy available to the market, now we have to figure out how we're going to pay for it, right, and how we're going to pay to ensure that patients are getting access to the therapies and some of these therapies carry anywhere from a US$300,000 to a US$2M price tag. Well, how in the world do insurance companies and payers pay for that if you've got, a hundred thousand patients standing in line waiting to get the treatment once it's been approved? And what we're seeing in the market is I think it fascinating and really uplifting that we have the payers actually working in concert with the sponsors to really come up with innovative payment models? Here in the US, certainly some of the challenges and this is where there's that underlying data layer again comes in, not just within the clinical trial process but moving forward into the long term following up that, as we know, can be up to 15 years, well how do you follow a patient for 15 years who's changing insurance companies every few years. If you change your employer, you change. We've got to be able to track those patients somehow, right? So that becomes a bit of an issue, and from a reimbursement perceptive it's the same thing, some of these payment models, we're looking at outcomes based, so, the manufacturer, the sponsor's not going to pay for the therapy if it doesn't work. There are annuity models that are being developed out there where maybe the payment is provided over several years. Well, outside of the US there's even a problem with those types of models because even in single payer systems, they form, they're out there looking at their budgets in a three to five year time frame, right, so if it's not in the budget how do we treat all these patients with these super extensive therapy? So, there's just a ton of work going on in that area and I see that that's not going to be solved anytime soon, it's a continuing dialog whether you're in the United States or outside of the United States.
Goldberg
Well I mean you've done I think an extremely good job of really starting to explain how the world is changing, and it feels like changes on many multiple fronts, and as you said, it looks like, even though there's a lot of work going on in those areas, it's going to take some time to sort it out. We're just in the midst of going through, , the COVID-19 pandemic, and we've seen, in a very short period of time, how much our worlds have changed because of that, how will we work, right, what we do with our friends, how we continue to go to schools and so forth. I'm kind of curious around how the pandemic has impacted cell and gene therapy clinical trials.
Joeckel
Oh, absolutely, and I'm proud to say that, we were able to keep our cell and gene therapy clinical trials on track, even during the pandemic, but to be honest, it did take a village do it for sure! It was definitely an all hands on deck, a lot of us were on speed dial with the sites, with the sponsors, but it was an interesting time, put it that way. Most of the things that affected our trials were considering site access and resources, right? You'll start from the very beginning of the process, access to the site, now we've got to have a patient that needs to go to a site to have the cells collected, so lots of changes, lots of additional patient safety, information. We had to open up new levels of communication with patients and their caretakers, just making sure that everyone was educated, everyone understood what the changes were and how to meet the requirements to have the site access. We had to ensure that site access resources were changed. We were constantly dealing with the fact that sites were reassigning people that we had trained in our cell and gene therapy trial to other COVID-19 initiatives that were going on at this site and so, we were constantly having to go back in and revisit the training, commercial airlines were grounded, how am I going to ship this product, these cells, where they need to go, we started to bring in alternative and multiple specialty couriers just in case we needed plan B because plan A gets canceled, so that became part of our now standard business continuity is to make sure that we've got backups, to make sure that we have multiple itineraries that are booked for these flights in case one is canceled. We already know one within the next three-minute time frame that we can the shipment on.
Then looking at delivery locations, that was the other thing, we literally had to start keeping a database of sites that were changing, we had logistics coordinators that were constantly contacting sites to go, is this delivery location still valid. Well no, we've actually closed that part of the clinic, we need you to go across campus now and deliver that shipment. And so, now that becomes part of the whole technology and alerts and notifications where the people that we had already set up with on our system that our data logger would alert that “hey, the delivery is on its way, it's within three miles of your facility,” well that alert was going to someone that wasn't even working on the trial anymore, and now we've got to change all of that. So, these are just, very complex moving parts that we were constantly having to stay on top of having to communicate, we had to revamp and redo communication and escalation pathways. So it wasn't an easy lift, I'll put it that way, and like I said, it really took a village and it was an all hands all the time.
Goldberg
But it sounds like you also, as an organization, learned and have adopted many things because of these experiences you've been through. You've said communications, escalation plans, continuity, and so forth. I'm just curious, again from your experience and observations, are there one or two things that you think the industry has learned from this pandemic and has adopted as you, and your organization, have had some really important learnings that have become part of your life?
Joeckel
Yeah, absolutely. I think that that's one of the things that we acknowledge right up front is that I would challenge that anyone had pandemic in their business continuity plans, and I will assure that it's there now. But it certainly changed the way we're looking at business continuity going forward, to just embed that risk mitigation now as part of our standard where we probably had something that talked about natural disasters, those types of things, but maybe not as specific as what we now have as far as the lessons learned. It really forced us to look at decentralized trials. It forced us to include options like, where can we include tele health, where can we include home health, how do we integrate that into our business processes going forward. And again, as I said, and I repeat it over and over again, executing these trials really requires multiple hand offs, it's not just of the physical cells and IP and the doses, but digital data and I think that's a lot of the work that you guys are doing and helping with, looking at how do I constantly move this time sensitive information amount diverse organizations that need particular pieces of it to make critical decisions? How do I make sure that that's available? And then underscoring all the time that the continuum here is patient safety, privacy, data security, how do I keep all of that in line? And these trials are patient centricity at is finest, and especially as we said in the beginning of this talk, in autologous therapies, the patient is the therapy, is the process. That's about as patient centric as you can get. And we just have to have from an empathetic perspective understanding that many times we're dealing with patients and families that are really frightened, they've probably failed what their standard treatments are and they're running out of options, and so having that communication plan moving forward is really, really important. Looking at these decentralized trials, risk space monitoring, , we've adopted a more flexible CRA model for the trials outside of the traditional model of just one CRA serving multiple sites. Maybe having multiple CRAs with the primary that covers a smaller number of sites. And that way you make sure that you've got people that are familiar and who are already vetted, who can monitor with us and allows us to be more flexible. And I think that one of the things that we're doing, also looking at decentralization and remote monitoring and management of the data is really important because there's just too many moving parts and there's too many critical areas at risk to safety that catching something light may have a much greater impact than on a traditional trial.
Goldberg
Tammy, you've just in the last couple of minutes touched on many interesting perspectives of what we're facing and some of the things that you're trying to address. So my question to you is that sounds like a really important and critical challenge to solving, kind of what do you see, or how do you see digital, and kind of investments in digital types of technologies helping to really reduce kind of the friction in those challenges that you've discussed, or the needs that we have?
Joeckel
Well that's an important part of cell and gene therapy. When you start looking at data, it behaves really differently in cell and gene therapies. In traditional clinical trials, data is coming in, somewhat evenly, through the course of the three, four, five, six years of the trial. In a cell and gene therapy clinical trial, you're literally getting 80% of your data in the first couple of months of treating the patient. You've got huge volumes of data that's coming in, and that is not just affecting data, that's affecting clinical trial execution, right? So now I've got to work with the site and make sure that we're forecasting the resources based on patient recruitment, now I can start looking at here's the level of data that's about to come in, how do I make sure we've got the personnel that's there to clean the data to meet regulatory reporting time lines. And so there's a huge data component there. As I said, we're looking at data that's coming in from so many different entities. We've got lab data, there's imaging data, there's data from not only within the clinical site. Now we're looking at outside third-party service providers that are providing data as well, and so how do we accumulate that? And within these trials we've got to be able to organize that information where we can make critical business decisions, right, so you've got to be able to make sense. It's not just bringing in data and putting it in a repository. It's creating dashboards that are meaningful, that are helping us not only execute the trial but helping us make really critical patient and product safety decisions that have to be there, so it's definitely, again, operating under accelerated time lines, data becomes a really critical piece, and then just looking at what levels of how can artificial intelligence maybe be integrated to help with site selection, patient recruitment, people don't understand that in the site selection so we've got to be able to look at the entire landscape of what's out there. You're looking at sites that may be doing a competitive trial to what you're trying to activate and recruit them for, is that possible, is it feasible, and so at ICON we've got an amazing feasibility group and that's a huge part of what they're doing is that they're helping us look at the overall landscape of the clinical trials. They're helping us assess and understand who's doing what work in which therapeutic area and then where those key opinion leaders are, where the investigators are that we want, and maybe helping us think outside the box a little bit instead of everybody going for the same five sites that they want for this particular therapy. How can we maybe look beyond that, and the same with patient recruitment especially. Think about patient recruitment for rare and orphan diseases. We've got to be able to identify where those pockets of patients are. A rare disease says it's rare, which means how do I find those patients. We've got to engage with patient advocacy groups. We have to have that type of data stream coming. We've got to be educated about where they are.
Goldberg
We’re almost at the end of time, and I wondered if I can kind of throw you a last, really broad question to really wrap up our time together, which has been extremely interesting and extraordinarily valuable, and really a perspective of the world around clinical trials that many people you've provided us, that many people probably don't have or don't have, the depth that you certainly have shared with us today. And so, the broad question really is focusing on, is there anything else you think our listeners might be interested in, understanding or learning more about, from a clinical trial process, as it relates to cell and gene therapies?
Joeckel
Well certainly I think I have a personal perspective on it. I'm a mother of a grown child with a rare disease. And so I think that's why cell and gene therapy is so important to me, it's certainly a big reason why I'm so passionate about making sure and ensuring that we continue to move forward with these potential curative therapies. I think from a public perspective, yes these therapies are expensive, we're doing things that everything that we can to make sure that patients have access to these therapies, and I think, again, that's going to take a village as well to make sure that these things are happening from a clinical trial perspective. Looking at, again, all the digital and media outlets that we have, to make sure that we're getting information out there about the clinical trials that are happening. Helping to raise awareness that this kind of research is going on, it's a meaningful time in the life sciences sector. It's an exciting time to be working on it, whether as we as ICON are executing the actual trials themselves, or working with partners like you that help with the digital strategies for the trials overall, It's just, I think it's something that I think the outlook is bright, and the future is bright, and I look forward to continuing to work for many years in this space.
Goldberg
Well, Tamie Joeckel, thank you so much for spending some quality time with us today. I am energized by your passion and your purpose. I want to applaud you and your organization for continuing to drive forward what I think will be really changing the trajectory of lives of many patients in the future, and it's really starting really at ground zero with the clinical trial work that you and ICON are focusing on. And so with that, and to our audience, let me say thank you very much, and looking forward to the next episode just around the corner.
