Cell and gene therapy insights

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Heidi: Cell and gene therapies bring the promise of personalized precision medicine to life. But the production and commercialization of these therapies is costly, intricate, and high risk—in part because most supply chain and manufacturing processes involve multiple stakeholders and facilities, coupled with variant cell and gene therapy life cycles and patient journeys.

Heidi: Moving forward, the industry may need to adapt historical processes, roles, and value chain organizational structures to be able to deliver their products successfully to patients. Welcome to Tales of Transformation. Today we have the pleasure of being joined by our moderator, Hussain Mooraj, Deloitte’s NextGen Therapy Practice leader; and Jacob Snapp, technical research and development, cell and gene therapy product strategy lead at Novartis; and Carrie Karlene, nurse manager, department of nursing apheresis at Mayo Clinic, to take a closer look at the cell and gene industry and how digital technology might allow organizations to successfully manage this complex, multi-organization stakeholder environment to ultimately deliver on the promise of personalized medicine in the future of health. Now I’ll turn it over to Hussain to get us started.

Hussain: First of all, I’m really lucky to be joined here by two really distinguished guests, Carrie and Jacob, both from the Mayo Clinic and Novartis. And I want to thank them personally for taking the time to sit down and have this fireside chat with me on this absolutely critical and important topic.

Hussain: I will begin by first asking Carrie and Jacob to spend about a minute or so introducing themselves, their background, and what they do and what gets them excited.

Carrie: Pleasure to be here. I have been with Mayo Clinic since 2016. I was actually introduced to apheresis prior to then. We have been fortunate enough to launch all six commercial products that are currently approved by the FDA [US Food and Drug Administration], so it’s been truly an exciting adventure just to see all these come to fruition and have more options for our patients, who before didn’t have options anymore. So, really, that’s an exciting factor for me and has been the driving factor to really make these collections successful and make this be a part of a successful program.

Hussain: I didn’t realize that you’ve had that experience of seeing all six of the therapies. Wow. Fantastic.

Carrie: Quite exciting. Quite exciting.

Jacob: Carrie and Hussain, great to be here with you. I joined Novartis in the spring of 2018 to stand up our global sales and operations planning capability for Kymriah®, our commercial CAR-T asset. Sales operations planning brings together the finance function, the commercial organization, and the manufacturing operations. So the confluence of all three of those business functions. I did that for roughly four years, and over the past 18 months, have transitioned into a role in our global drug development organization focused on bringing our next-generation CAR-T assets through clinical development and hopefully to commercial realization.

Jacob: So, I have experience in CAR-T on the commercial side, manufacturing ops, and then now on the clinical side, working to bring these next-generation products to market.

Hussain: One of the things that I’ve been noticing these days is that in the cell and gene therapy [CGT] market, it’s really hard to raise money even though you’ve got good science, solid data—finding it super hard to get a lot of these therapies to the marketplace. And in response to that, we’ve been asked to see how cell and gene therapy has been doing over the last few years. So we came up with the cell and gene therapy market index. And what blew us away was that if I’d invested $10,000 in the Deloitte cell and gene therapy market index, today I would’ve made $100,000 in that and only $50,000 if I’d invested it in the S&P pharma index, and less than a third of that in the biotech index.

Hussain: So as hard and harsh as the market looks today, if we take a look over the last five years and how the market’s been doing, it’s actually … true science has broken through, and people with companies, with good data, have actually been able to commercialize their therapies. What I would love to really understand from you both is what is the current state of the CGT marketplace? Do you feel good about this area, in terms of the depth of research, in terms of the innovation?

Carrie: I feel like we’re at the tip of an iceberg now. That’s, It really becomes a debate. Who can we help? Which clinical trials do we onboard? What do we need more of as far as diseases go? Do we have enough as far as, say, lymphomas or leukemias?

Carrie: Let’s look at what we have in our pot so far, and how do we diversify and bring more products in to help a broader spectrum of patients. So that’s been something that our research department has really taken a look at. And then now with the introduction of solid tumor and pills and all that. So we’re really looking and trying to figure out, as an enterprise, how do we diversify this to meet the demands of such a variety of people?

Carrie: So, it’s very exciting, but how do we manage that to make sure that we are doing what’s right by the patient, having trials that are safe, and hopefully effective to provide a treatment or a chance for a treatment for them. So what does that look like from a manufacturing standpoint? What’s the turnaround time?

Carrie: Are we going to be able to get them in a time for the patient to be able to have a therapeutic effect? So, it’s really not just a one-avenue answer; it’s really pulling in everything from around you and trying to piece that puzzle up together to try and make the best picture you can for yourself as an institution, but also for your patients, obviously, which are the primary focus of all of this.

Hussain: Brilliant, well said. Jacob?

Jacob: Novartis was the first to launch a commercial CAR-T product in B-cell lymphoma. Shortly thereafter, [Gilead’s] Kite was able to bring their product to market, and subsequently Bristol Myers Squibb. We’ve seen this CAR-T therapy and B-cell lymphoma get approved as a treatment option for second-line therapy, so it continues to advance.

Jacob: We as an industry are bringing more of this therapy to market. I know we’re all focused on bringing additional indications through the clinic that we can use cellular therapy to treat other types of blood cancer. So, it’s a very exciting time.

Hussain: You’ve been at this for a long time, like Carrie, since the first launch of Kymriah.

Hussain: You guys were the pioneers in this space, so you’ve seen it all. What have been some of the biggest changes that you’ve seen since that first initial launch when Novartis had to, like, come up with everything new through either a complete new frontier versus the second, the third, the fifth therapies that were launched after that?

Jacob: Again, on a macro level, the additional competitors in this space. That’s been one of the biggest changes working through initial challenges with product quality. When we launched Kymriah the first year, we had trouble manufacturing the therapy and producing it on spec. We were able to successfully work through those challenges, and we’ve seen some of the same issues with manufacturing capacity and off-spec product with the competitors.

Jacob: Everybody’s had to go through this teething period, if you will, to stand up these therapies and bring them to market. As a manufacturer, it’s been difficult to figure out the right balance between external supplies using partners to manufacture for specific markets, and making that investment in internally figuring out what the right calculus is for CAR-T manufacturing capacity. It takes a long time to bring online, it’s labor intensive. So that’s been one of the big changes. And then thirdly, I would say, the viral vector manufacturing. So, the viral vector, it’s key starting material for these cell therapies, and Novartis has used exclusively contract manufacturers or business partners to manufacture viral vector, and we’ve observed a pivot—at least with the big three—that companies are now bringing this capability in-house and want to have greater control over viral vector manufacturing and hopefully reduce that lead time it currently takes in the range of nine months to manufacture a batch and go through quality release before we have it onsite and are able to use it for patient treatment. So that’s been the other big pivot in the last five years is exclusively using external contract manufacturers to bring this capability, vertically integrating it within the manufacturing supply chain.

Hussain: The manufacturing piece has certainly been one of the biggest challenges in successfully taking these therapies to patients. Carrie, from your perspective, with the number of commercial cell and gene therapies in the market today across a variety of manufacturers, what do you think the current benchmark of an excellent customer service experience looks like?

Carrie: I think it really all boils down to good communication. Good communication between the providers at the site with our patients, and then also with the manufacturers, with our providers.

Carrie: We need to be transparent in those communications and open and honest about them. I think these patients come in and they know that this is not a 100% guaranteed treatment for them. So what they’re expecting from us is a communication. “OK, this is where we’re going. This is our set plan for you.” Once we go and collect that cell matter, unfortunately, I feel sometimes we’re in the dark a little bit. So we aren’t able to give those exact updates to the patients to say, “OK, your cells may have started manufacturing, or they’re successfully manufacturing.”

Carrie: So I think there needs to be some work in that communication between a manufacturer and a provider—and it’s not always disclosing proprietary information. It’s just a checkpoint system along the way, and then we’re able, in turn, to deliver that to the patient so they have an expectation of what could be coming down the line.

Carrie: Are we set to do some bridging therapy with either chemotherapy or radiation, or did we just have a bad starting product? Do we need to look at recollecting, or do we need to look at some other therapies to try and figure out what we need to do to recollect you again to get, say, an ALC count up to where it needs to be, to provide a good starting product for the manufacturer. The communication that needs to take place between all the parties that are involved in this process.

Jacob: I couldn’t agree more with what Carrie’s saying around transparency, the hospital side, or the patient. It goes into a black box, and they wait 15, 20, 30 days before their therapy is returned. There is real opportunity there for a manufacturer to provide more information as the patient cells are going through manufacturing, and what that status is, and how we could update the hospital site or the prescriber and the patient.

Jacob: What does good look like for a manufacturer? We need those cells to show up on time. We only have a finite amount of manufacturing starts every day, and if they haven’t been received and prepared to start the manufacturing process, that’s a missed opportunity to start another patient. We don’t have inventory of patient cells that we can pull in to fill that capacity.

Jacob: Having those patient cells show up on time, beginning the manufacturing process on the date that we promise the prescriber or the hospital, and then successfully manufacturing the batch that it’s within our manufacturing specification, returning it back to the hospital site for administration and infusion.

Jacob: That’s what good looks like from a manufacturing standpoint. A lot has to go right, though. Think about this ecosystem: It’s the hospital sites, it’s the carrier, the logistics movements. It’s moving the batch through our manufacturing process, having an on-time quality release, and then returning those cells back to the hospital site on time and delivering on that promised date. It’s a complex supply chain.

Hussain: Carrie, from your perspective, part of good communication comes from a level of transparency in the value chain. Part of that is delivered through the digital capabilities such as portals that enroll patients, scheduled patients, etc., which each manufacturer puts forward. With the tsunami of different products coming towards a clinician such as yourself and your colleagues—now potentially dozens of portals that you have to deal with—does this add to the complexity in the life of a clinician that’s yet another system of record? That you have to feed information into or keep checking?

Carrie: I have an app that has no less than 30 passwords in it, and sign-ins for the variety of portals, drop boxes, for me just to do my job. So it’s not sustainable. It’s highly frustrating, and every time I turn around, I’m getting a ping that, “Hey, your password’s expiring. You have to set up a new one!” There needs to be a better platform. There needs to be a platform that the majority of these sites can go to that still allows them to maintain discretion, not disclose proprietary information but allows the users and the providers a single platform to go to or a decreased number of platforms to go to.

Carrie: Nothing is more frustrating when you’re sitting there with a product or you have a patient that’s ready to get on and they’re like, “Oh wait, we have to send you a push to make sure you can sign in to our portal!” And now you’re delayed by 10 to 15 minutes because of the firewall to come into the facility.

Hussain: Something that we’ve developed that’s called CGT Vantage, [for] clinicians, providers like yourself, who basically said exactly that, right? We’ve got to make it easier for the patients. Let’s have one universal portal. Or fewer pockets. Right? So that we don’t have—we’re not carrying 30 passwords, but we’ll carry three, right, which is more manageable. That said, Carrie, what we’ve seen in the marketplace is that even though providers want that, it is really hard to get providers … to get them to agree on something. Or if it’s not mandated, then strongly recommend different technology. How do we overcome that impact?

Carrie: I think we really need to get out of our own way.

Carrie: I have things that I’m like, “This is how we do it. This is the best way to do it.” But I think we have to open it up a little bit more and be more open to generalizations and realize that just because we do something one way doesn’t make it right. There can be multiple ways to do a thing correctly and still get the information that needs to be there and still provide a safe patient treatment, still have an effective chain of identity, an effective chain of custody. But I think everybody just needs to move past themselves for the greater good.

Jacob: Do you think the hospital sites are eventually going to be the ones that mandate that? If Novartis wants to work with the Mayo Clinic, they’ve got to transition to this patient orchestration platform? What’s going to be the tipping point?

Carrie: It may come from an institutional-based demand, especially if it is seen as a safety risk or a risk to the patients in one way or another. If it ever comes to the point where we’re not able to provide the best care for the patients because we are inhibited by platforms or certain functions, then yes. Then we will probably band together and say, OK, this is what we need—and this is what we need from our providers, our manufacturers, to come to the table with.

Carrie: I don’t know how far away that is, if that’s something in the near future. I would like to push for it in the near future, but that’s just me, from one perspective. And I know my nurses that do the collections are in the same field as I am. They get frustrated as well. So it’s going to be really finding those people that are able to speak up and get their voices heard in this.

Carrie: And how we bring them together to speak as a unified voice. I think if it was up to the manufacturer, you’re like, well, I got a portal and it works, and this works for me. When you’re dealing with an entourage of them from our side, it’s not best practice.

Jacob: Seven years ago, portals and patient orchestration platforms didn’t exist. They had to be developed from the ground up to be able to support the initial clinical trials and then the eventual commercial launch of these therapies and multi-site manufacturing, support multiple clinical trials. But you’re right. We have a portal that we think works and works well. We’ve done multiple voice-of-customer workshops with key accounts to try to get feedback on what could be better, what capabilities the hospital sites want to see, and we’ve re-platformed our entire patient orchestration platform to include that feedback.

Jacob: But, yeah, it probably … it’s not sustainable. [We] can’t ask hospital sites to work with 10 different IT platforms. We wouldn’t think it would be anything patient safety related within our IT infrastructure, but yeah, I’m not sure what the tipping point would be to get all the manufacturers to coalesce on a single IT solution or a couple of them.

Hussain: Or fewer! Yeah, exactly. As you see therapies moving into these earlier lines of treatment and thus an increase in demand for the manufacturers, how do you see the manufacturers coping with this, given that cell and gene therapy is so hard to scale sometimes ’cause the number of patients is going to increase exponentially as you move to second line, and then hopefully, over time, the standard of care at some point. But that’s going to mean a drastic increase in the number of patients. That’s going to also mean that you’d better have your manufacturing lined up, or some patient’s not going to get their therapy somewhere. So from an industry perspective, there has been an acute shortage of manufacturing capacity in this space. What are you seeing in terms of maybe some technology innovations that are coming or maybe in just process and capability innovations that are coming that will help here?

Jacob: Along those same lines, there’s other personalized medicines that we’re bringing to market that have a different set of requirements that need a patient orchestration platform.

Jacob: So do we build again, or do we enhance and modify the existing plane that we’re trying to fly and use that to support ongoing commercial therapy and clinical programs? So it’s one we wrestle with.

Hussain: We see this cliff coming, from an industry perspective, where there’s a shortage of—massive shortage of—capacity as we move to earlier lines of treatment.

Hussain: And not just on the manufacturing site, but Carrie, from your perspective, the—I’m going to flip the earlier question—do you have the required resources, the beds, the staff, to cope with this added load of patients, which require this white-glove handling for these curative therapies?

Carrie: Some of these therapies have such a minimal, if nonexistent hospital stay, so that they’re able to be administered on an outpatient basis where we just require that they stay within a certain vicinity of the hospital.

Carrie: They still come in for daily follow-ups. So really turning that model into an outpatient model versus an inpatient model has been instrumental for us. We’ve been able to have a cellular therapy clinic where these patients are dedicated to come in to this specific clinic where we have these resources that are trained to deal with the patients and it doesn’t overburden the inpatient nurses because somebody had to sit there for two weeks. It’s all going to depend on how fast we’re growing in our ability to meet the demands. We all know nurses are not very easy to come by. We’re trying our best to make sure that we’re a site that a nurse wants to come to work at and be a part of.

Carrie: And the same with the providers—making sure we have enough providers. It’s interesting and it’s very complex. There are no easy answers, so [it’s] really a balancing act on finding everything that you need to make this work. And then when you think you have it, it changes.

Hussain: In terms of different business models coming in here, do you think it’s going to help you scale as a provider? So, for instance, there’ve been a number of discussions that I personally have been in where we talk about apheresis from a factory model perspective, where should we be thinking of taking apheresis out of the provider service? Just like you have in nephrology, you’ve got dialysis being done on a factory model, which used to be many years ago in an inpatient and outpatient model in the hospital system. Now you’ve got these big facilities where you run it as a factory. Would that ease and help, or is that just going to add to the complexity?

Carrie: No, it’s hard to say. Right now, just short-term thinking, I think it would really … it might add to the complexity because you have all of these prequalifications that the patient needs to meet.

Carrie: So you’re checking infectious disease markers, you’re doing chest X-rays, your EKGs, staging. All of that has to be done, and a lot of that really just for continuity of care is all done here at one spot. So then to turn around and then to, for lack of a better term, “farm out” the apheresis portion, does it really make sense? Or does it make sense, just for continuity of care, let’s keep it all housed together as a one-stop shop. So for me—and, of course, I work at an institution where this is what we do, and along with some other things—for us, it makes sense. Now, out in the rural community, it might be an option where it is actually done at a free-standing apheresis clinic, if they don’t have the ability to come in and have all the testing done in a synchronous order or a condensed time frame.

Hussain: Let me turn this around to you, Jacob. In terms of bedside manufacturing, is it the future or is it a fable?

Jacob: I think it’s a fun topic to talk about and hypothesize, but when you really dig into it, I don’t think it’s possible. Can you set up the automated manufacturing, put the inputs into the machine and patient’s white blood cells?

Jacob: Yes. But it’s all the supporting functions—the lab work, the quality control. The regulators are going to expect that the manufacturer has full responsibility for that. And when it’s bedside, I don’t see the pharmaceutical organizations signing up for something that’s outside of a GMP [good medical practice] environment.

Jacob: But it’s, yeah, it’s a fun topic to hypothesize about and talk about, but I don’t necessarily see it coming to market in the near term. The leukapheresis collection, though, outside of the hospital: There is one big pharma company that’s looking to leverage their internal capability and perform leukapheresis within their blood collection centers. Like Carrie mentioned earlier, these patients are often in very poor health and require bridging therapy and need to be within close distance of a trauma center if something goes wrong. I think there’s opportunity there to relieve leukapheresis or cryolab capacity for some of these sites, but we’ll see. It’ll be a very different environment two to three years from now than what we’re operating with today.

Hussain: Moving towards the end of this discussion, Jacob, you brought up the regulators again. We have the Deloitte industry working group, which meets on a regular basis, and we try to raise the tide for the entire industry through some of the great work that all of you do. I was on with Peter Marks last week (of the FDA), and he has agreed to speak at the next one in person in September in the DC area. Peter came out with a phenomenal statement a few weeks ago in which he shared that the FDA needs to really approve a lot of these therapies on an exponential basis. Right? Not even just a little bit of a progression, but he really wants to up the ante. And what he was saying to me last week was three years ago, there was a great level of energy around cell and gene therapy, and money was being poured into it. Great science, people were all energized. It was the place to be. And he feels the slowdown in that energy. And that is exactly what the FDA does not want. The impression that the FDA does not want to give to the market [is] that the FDA is slowing down in any way with regards to approving a lot of these curative therapies in the marketplace, which is fantastic because, as one CEO said to me, in five years, he expects this to be the dominant therapy in the marketplace. That’s pretty aggressive. I can see that happening as well. And with that, it comes to my last question. You guys have been so wonderful that I’m thinking of just keeping on going, but I know that we’ll get shut down in a couple of minutes.

Hussain: If you could leave our listeners, Carrie and Jacob, with one takeaway about the future of personalized medicine, what would it be?

Jacob: We’re 100% focused on the patient. I know that gets bandied around a lot. Everything we’re doing in the clinic and cell and gene therapy right now is focused on bringing new therapies, new gene therapies, new cellular therapies to market.

Jacob: We want to bring more curative therapies to market. We’re going to continue to invest. We see the value in these therapies, and personally I’m focused on how can we cut the current manufacturing, the current vein to door time from the current standard, which is anywhere from 22 to 30 days, to getting that under 10 days. We think that’ll be a game changer.

Hussain: That’ll be a game changer, for sure.

Jacob: To Carrie’s earlier point, it’s not something that the manufacturer can do itself. It takes all the partners in the ecosystems. It starts with the hospital and the leukapheresis, the business partners that we work with in the logistics space that move these cells. Each one of us, we’re looking at where we can cut days and hours to meet that goal.

Carrie: Jacob said it well. It takes all—and a lot of—moving parts to make this work together for the effort of truly personalized medicine. Make sure that no matter where you are in the realm, that you have open and transparent communications with everyone involved to help make this journey for the patients so much better for them.

Heidi: Cell and gene therapies have certainly emerged as one of the fastest-growing sectors within the life sciences industry. But the life cycle of these next-generation therapies is much more complex than traditional pharma products, requiring more stakeholders and touchpoints to deliver on that promised state.

Heidi: We want to thank our guests, Jacob Snapp and Carrie Karlene, and our special moderator, Hussain Mooraj, for your time today, exploring the near-term potential of innovative technology candidates accelerating us towards the future of cell and gene therapies and the future of health.

Jacob: It was my pleasure, absolutely fantastic conversation with Carrie and Hussain, and I look forward to additional collaboration with both of you.

Carrie: Thank you for inviting me. Thoroughly enjoyed the conversation today, Jacob and Hussain. I respect you guys, and I appreciate the thoughts—and something to think about moving forward.

Hussain: Thank you, thank you, thank you. This has been a wonderful discussion. I could not thank you both [more] deeply from the bottom of my heart for all that you do on a daily basis.

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