Expanding Access to Cell Therapies with a Patient-Centric Focus

Expanding Access to Cell Therapies with a Patient-Centric Focus

March 12, 2022PAO-02-022-CL-12

The explosive growth of adoptive cell therapies and growing interest in allogeneic cell therapy treatments have created a need for donors and the infrastructure necessary to manage the collection and movement of cellular materials and the gathering and tracking of patient data. Amy Ronneberg, CEO of The National Marrow Donor Program® (NMDP)/Be The Match® and Be The Match BioTherapies®, shares her thoughts on current trends in the adoptive cell therapy space, the challenges the sector faces, and how Be the Match® is helping to facilitate further advances in the field, with Pharma’s Almanac Editor in Chief David Alvaro, Ph.D.

David Alvaro (DA): How would you characterize the current moment in the cell therapy space overall?

Amy Ronneberg (AR): The industry as a whole continues to grow at a rapid rate, and financing is still incredibly strong, though the public markets have cooled a little bit recently. The number of years with such a strong flow of dollars into the sector underscores its strength. We are seeing more and more allogeneic — or off-the-shelf — treatments being developed as opposed to autologous patient-specific therapies. That trend is really a direct reflection of the high price point for autologous cell and gene therapy. In fact, the high price of autologous therapy is continuing to create an even bigger gap from a disparity perspective between the insured and the uninsured. At Be The Match®, we are certainly welcoming the allogeneic, off-the-shelf space and continuing to partner with a lot of different organizations in that space.

DA: What are the fundamental differences and challenges in the supply chain for autologous and allogeneic cell therapies?

AR: In the allogeneic space, one of the biggest challenges is consistently sourcing high-quality, compliant starting material. There are other organizations like Be The Match, but we are fortunate to have definitely the largest and most diverse donor registry in the United States. We have about nine million well-typed donors, including HLA type, ABO, CCR5, CMV status, etc. We see a broad range of specific requests regarding donor characteristics from companies resulting in thousands of donors meeting the requirements to a very small population eligible to participate.

The COVID-19 pandemic has created additional challenges in the supply chain for both autologous and allogeneic therapies. Many potential donors want to help, but they may not want to enter a medical facility to donate right now; it’s not the time. At the same time, we see thousands of people stepping up to help patients in need of a lifesaving therapy.

The coordination between the collection of donated cells and manufacturing slots continues to be a challenge. Capacity is expanding, but there still is a lack of manufacturing slots. The supply chain for autologous therapies is very different from that of a conventional drug. Every single therapy is its own batch that starts with collecting cells from the patient, and this requires careful coordination of the collection, manufacturing, and administration. One of the main issues is that we are dealing with human beings, and things change with human beings on a constant basis. For instance, when the initial scheduled day for cell collection for an autologous treatment arrives, the patient may be too sick to donate, which means that changes have to be made throughout the whole supply chain.

DA: What key innovations over the past couple years have made allogeneic cell therapies more feasible?

AR: A couple of important developments are converging. As the amount of data has grown, the strength of predictive analytic platforms that can be used to determine that one-to-many match has increased, along with the ability to use that data from a personalized perspective, even though it remains one-to-many. Genomics technology also continues to expand, making it possible to edit and match donors and patients, even beyond a full allogeneic perspective. I think we’re going to continue to see even further revolutionization of precision medicine, even for transplantation, which continues to be one of the most widely used, if not the most widely used, life-saving cell therapies. The question is: How do we create even more matches that go beyond the human leukocyte antigen (HLA) matching approach and start to get into specific antibodies or factors that are specific to the disease? The Big Data analytic platforms based on genomic data, machine learning, and artificial intelligence are continuing to advance at a pace that will allow even more precision.

There is also a lot going on right now in the point of care, which is critical as we talk about the democratization of cell therapy and closing the gap. Having different platforms for point-of-care will allow a broader set of patients to benefit from cell and gene therapy in the future. That development in particular has been the source of an incredible amount of hope and optimism for our organization. As we continue to see more therapies reaching phase III and commercial status, it’s going to create so many opportunities for patients. But there will also be increased supply chain challenges with the current use of many different IT platforms, creating inefficiencies in an already overburdened system. Transplant center coordinators, for example, have to learn five, six, or more new systems to provide multiple pharma company’s therapies. That simply is not sustainable. We have to come up with some type of universal platform that can be used whether the therapy is at the research stage, in clinical trials, or a commercial product. 

DA: Is there a relatively clear path to realizing such a universal IT platform, or are there challenges that must be overcome?

AR: The companies that already are commercial have invested millions of dollars into their branded systems, so it is difficult to expect them to retire those platforms at this stage. I think everyone agrees that a universal ordering platform is needed, but no one can agree right now on what that should look like or stop using their own developed platform.

The American Society for Transplant and Cell Therapy (ASTCT) has a group called the 80/20 Group, which Be The Match is part of. The group is focused on the fact that these different technologies are ultimately 80% similar from a supply chain, material flow, and chain of custody / chain of identity perspective. The goal, then, is to create a system, at least on a go-forward basis, with that 80% being the same for everyone and the remaining 20% customizable to meet specific product/program needs.

There are a lot of players and really smart people working on this concept. The industry simply needs to come together and commit to using one platform. The same issue existed in the transplant industry 30 or 40 years ago. Every registry in the world used its own IT system without the ability to perform a world-wide search. Phone calls had to be made each time there was the possibility of a donor match somewhere else in the world. Today, all of those registries have been brought together. Hopefully, we can get to that point more quickly with cell and gene therapies. 

DA: Where are there still significant gaps and/or bottlenecks in the infrastructure needed for the manufacturing, distribution, storage, and administration of cell therapies?

AR: The biggest gap is the lack of infrastructure for end-to-end support from ordering to data collection. Whether patient outcome data or operational data, there are just too many different systems right now. Even the manufacturers have to work with multiple systems.

As an industry, we need to figure out how to coordinate all aspects of the process. That means that some players will need to give up the proprietary systems they have created, which is a really difficult ask, because they have invested a lot of money in those systems. At Be The Match, we can help facilitate the movement to a single platform, because as a nonprofit we can be an honest broker to facilitate interactions between the different transplant centers, manufacturers, and cell and gene therapy companies.

DA: With respect to sourcing for allogeneic therapies, how universal or fixed are the criteria for matching donors to patients? Are there still opportunities for finding other biomarkers? Or are requirements already more stringent than they need to be?

AR: In many cases, the therapy itself determines the level of precision needed. There are many different source materials being used, different targets, and different routes of administration. Some of these therapies need very little precision with respect to HLA — the requirements may relate to other genomic or phenotypic characteristics of the donor. In other cases, the requirements with respect to HLA are very specific.

Be The Match® is conducting studies right now with our ACCESS Trial, and we are finding that, with the administration of post-transplant cyclophosphamide, several HLA mismatches still produce successful outcomes. That is where personalized medicine and Big Data come into play; we need to better understand different antibodies and different reactions to different medicines to continue to improve outcomes.

DA: To rewind a bit, can you relate a bit of the history of how Be The Match BioTherapies emerged from within the longstanding Be The Match organization?

AR: Be The Match itself, as you know, has been facilitating transplants since the 1980s.  The creation of Be The Match BioTherapies was a response to trends in the industry combined with the recognition that we weren’t able to serve every single patient. There are about 18,000 patients in the United States each year that would benefit from a transplant, yet only about 6,000 get one. We wanted to be able to serve every patient. Many of the 12,000 people not receiving transplants are too sick to undergo the intensive transplant process, resulting in the need for other cell therapies as a bridge to transplant. 

We have mastered the ability to move product regardless of what is going on in the world, creating a big differentiating capability of Be The Match. Whether borders close because of a pandemic or an ice storm shuts all of Texas down, we make sure that we still move that product every single time. The genesis was the notion that we could leverage this capability to support autologous cell and gene therapy manufacturers that lacked this capability and expertise.

We also recognized the need for starting materials for manufacturers developing allogeneic therapies. While they could go to providers without HLA-specific knowledge, the database that Be The Match has is highly differentiated by the level of HLA and other typing data that it contains for a very large number of donors. The third realization was that, for autologous cell therapy manufacturers we have a network of over 80 apheresis centers that could be plug-and-play — as opposed to requiring individual contracts for each site.

As we talked to more and more companies, it became apparent that there was an opportunity to fulfill our mission, which is to save lives through cell therapy. It didn’t matter if the treatment was a transplant or a different type of cell therapy; getting involved in the cell therapy sector would help us fulfill our mission.

DA: Beyond access to large numbers of donors and the ability to efficiently collect and move cellular materials, are there any other differentiators that help Be The Match BioTherapies stand out in the marketplace?

AR: The Center for International Bone Marrow Transplant Research® (CIBMTR) is definitely another differentiator. The CIBMTR is a department within Be The Match and a department within the Medical College of Wisconsin and has collected clinical outcomes data points on over 600,000 patients. Our data can include as long as 30 years of data for a patient and includes patient data from all bone marrow transplant centers in the United States.

Today, our outcomes registry also includes several cell and gene therapy companies including all FDA-approved therapies. Others can say they can collect and track data, but we have a track record of successful performance for 50 years for allogeneic transplants that have occurred during that time. I think that really differentiates us. In fact, Be The Match has been awarded every single autologous CAR-T long-term follow-up patient registry from the commercial entities that exist today. 

DA: With advances in adoptive cell therapies occurring at a rapid rate, is Be The Match choosing to focus on CAR-T cell therapies, or are you interested in exploring the huge panoply of options?

AR: We are agnostic to the therapy. It is about helping patients receive their lifesaving therapy. Be The Match® has six areas of specialization, and if we are positioned to help a company with the development and commercialization of their therapy through those areas of expertise, we will partner with them as long as their therapy is lifesaving or life changing. That is important, because we are not locking ourselves into just CAR-T. If we’re able to help an organization move forward and save more lives, we’re going to do that. For us, it is about the number of lives that we can impact. 

DA: Is there anything in your own personal background that helps you manage these challenges or helped shape your vision for Be The Match BioTherapies?

AR: I share this because I think it does change how I lead. I am a cancer survivor myself. I know what a patient goes through, what a family goes through. To me, it's all about doing everything we can and never taking no for an answer, because there is a patient on the other side. We constantly talk about making the impossible possible and doing that every single day because, again, there is a life on the other side; it’s not a number. It’s about a person who could be a grandmother, a grandfather, a father, and is looking for that next day so that they can have that experience. As a result, Be The Match is very much a patient-centric organization. The decisions are always made and resources allocated based on what is best for the patient.  

When COVID-19 hit and we realized we were going to have challenges everywhere, we had one true north, and that was: every patient that starts their conditioning regimen, their chemotherapy, would have those cells arrive on time. Every decision was focused on making sure the lifesaving cells were there for the patient. There were times when we had to get a private jet or a private helicopter to move cells. But it was critical that we did it, because there was no other option.

I think I bring a very metric-driven, very results-driven experience from my finance background, but my personal experiences layered on top of those numbers help me always stay focused on the fact that we are doing what we are doing to save lives and bring hope to patients.

DA: Can you tell me a little about the companies you partner with and how being a nonprofit influences the partners you seek out?

AR: It starts with the culture, as any partnership needs to have a similar culture with a shared mission and vision. Be The Match is very patient-centered, and that has to be the case for anyone with whom we partner. addition, any partnership must at its basis help enable Be The Match to serve patients suffering from life-threatening and debilitating diseases — starting with those 18,000 people that need lifesaving transplants and now expanding to broader patient populations that also might benefit from our unparalleled passion, focus, and experience in cell therapy. Naturally, we also look at the science, the technology, their financial viability, the things that you would with any partnership — but it starts with that shared mission/vision and being a really patient-centered organization.

We have partnered with many different types of organizations ranging in size and maturity, and the relationships that we establish often reflect the different needs these different types of organization have. Some may use just one of our services, while others work with us from cell sourcing to establishing and managing a collection network, to supporting the movement of product, and finally data collection. Again, we will partner with therapy developers if we are able to really help that core base of patients that Be The Match was founded to serve, whether they need to use one or all of our services.

DA: Given that COVID-19 continues to be a challenge for the world on every imaginable level, I wanted to talk a bit about the complications it is causing with respect to sourcing and the delivery of the services you offer. What have been the biggest issues for Be The Match BioTherapies?

AR: We talked about logistics and border closings, which was one of our biggest issues to start with. But the logistics have continued to some degree in that flights just aren’t as prevalent. As you know, there were times around the holidays when thousands of flights were canceled, mostly because pilots and staff were testing positive with COVID-19. FedEx and UPS, which we use for some of our cold chain, have at times also experienced shortages due to their staff having COVID-19. Given the importance of timing with our products this has been an “all hands on deck” situation to solve for these issues as they arose.

There are issues in the transplant centers as well. A large number of nurses, physicians, and lab techs have not been able to come in at times because they have COVID-19, which forces the centers to prioritize patients. There are also shortages in supply chains, whether it’s EpiPens to administer filgrastim or filgrastim itself. The same supply chain issues that are happening everywhere are happening here in this space, and that just creates an incredible amount of extra work. I would say everything is about ten times harder today than it was pre-COVID-19.

We also have donors who have a fear of going into a facility, and I can absolutely appreciate that. There are still an incredible number of donors that are stepping up, but some of them end up testing positive when they go through the workup. That creates the need for significant changes in the plan that was in place for the patient. Basically, everywhere we turn right now, COVID-19 is impacting the healthcare system in one way or another and thus impacting our work.

However, our incredible partnerships have been important in dealing with many of these issues. We have partnerships with government agencies, suppliers, and financial contributors that have gone above and beyond to help with pandemic related issues to ensure the patient received their lifesaving cells. When certain transplant centers or cord blood banks have had shortages, we have been able to put out a call to action and — by working with our network of partners, other transplant centers, and other players in the industry — help really move things around to mitigate some of those shortages.

DA: Do you see any innovations on the horizon in the next few years that will be really disruptive or transformative for cell and gene therapy in general and/or the ability of Be The Match BioTherapies to better serve patients in need?

AR: As we collect more data and learn more, we’re going to have to continue to evolve. Getting back to genomics and the understanding of that precision, personalized medicine: we’re going to have to keep up with that and evolve. I think there is also an expectation for all organizations to have the same type of — and this might sound odd to what we do — but that same type of customer service that Amazon has. We expect immediate feedback, and we expect immediate information, and we need to make sure that we are staying up to those standards and that our transplant centers and our manufacturers have the systems in place so that every step of the way they are able to see where we are in the patient and donor journey.

In addition, I don’t know if it will happen in the next year or the next two years, but I strongly believe that Be The Match has an absolutely critical role in bringing about the universal ordering platform. We need to make sure that we’re at the table to help transplant centers and coordinators so that the number of systems they have to work with doesn’t double in the next two years. We may not be able to walk back the five or six that have already been implemented, but from a go-forward perspective we need to help make the necessary changes.

The biggest disruption for Be The Match — and it’s a positive disruption — may be the access trial that we call “Donor For All.” If we can show that a donor whose HLA match is a six out of eight or a seven out of eight, has incredibly positive outcomes with a post-transplant cyclophosphamide regimen, then an African American patient that today has a 29% chance of finding a suitable match would suddenly have a 99% likelihood of finding a suitable match — hence ‘donor for all. Of course, a physician may still say they prefer a CAR-T or another type of adoptive cell therapy, and we’ll remain agnostic to that. But the fact that a donor is out there for every single person would be just an absolute game-changer.

DA: Looking even further out, where do you see the ultimate promise of cell therapies within the continuum of care? And what will be the role for Be The Match in that future landscape?

AR: I think in my lifetime — I’m not sure when, but in my lifetime — precision medicine will lead physicians’ decision making. We are absolutely headed in that direction, and it will only improve patient outcomes when we can personalize the entire transplant journey.

How do we get to a point where that apheresis can be performed at your house, or when we can do more from a home perspective as opposed to having patients need to go to a facility? I think again in my lifetime we’re going to see a lot of change there too, at that point of care.

All of these impact Be The Match. We need to be at the forefront. We need to make sure that we’re continuing to do the research, and particularly that we’re really owning what’s in that bag, that we’re bringing the absolute best cells and product to that specific patient. So, we are going to continue to invest a lot in research. We’ve got the data — 600,000 patients’ data to use for retrospective studies and continue to do prospective research to make sure we’re at the forefront.  

DA: If the cell therapy work that you do is incredibly successful, will that eliminate the need for transplants?

AR: I don’t think so. I think it’s a complement in a lot of ways. Sometimes it may be a bridge to transplant, where the patient is too sick to undergo the conditioning that occurs with a transplant. Sometimes it is a complement in that it reduces other types of infections or reduces graft-versus-host disease, making transplants more successful. Again, if we were already serving all 18,000 patients, I might be more nervous from a market share perspective. But there are thousands of patients just in the blood cancer space alone that aren’t getting what they need. We have so far to go here in the United States still. We are therefore going to continue to grow both traditional transplants and cell and gene therapy. The day that we’re at all 18,000 patients treated will be a day that our organization celebrates.

DA: Are there any last thoughts you’d like to conclude with?

AR: The key really is that our organization has pivoted a lot. Pivoting is part of every single day of our lives, because something’s getting thrown at us in a different way. I just couldn’t be prouder of this organization and the people working here. They continuously deal with the unexpected and are successful despite having to constantly deal with the unknown. As an example, despite COVID-19, last quarter we increased by 7.5% year over year more patients than we facilitated. That’s over 120 more patients that had a lifesaving cell therapy. This organization has not shied away from the challenges — if anything, we stepped up. We have found new and innovative ways, and I expect that to continue regardless of what’s thrown our way.

chat button