Alliance for Regenerative Medicine (ARM)
BioMarin
ifteen of the top 20, or 75%, of the largest pharmaceutical companies by market cap are actively involved in cell and gene therapy,” explains Timothy Hunt, chief executive officer at the Alliance for Regenerative Medicine (ARM). “These companies are also looking down the road at things like cell therapy in autoimmune disorders, cell therapy in solid tumors, and gene therapies in more prevalent conditions. There is significant potential in these areas, and these investments by the larger biopharmaceutical companies are pretty clear.”
“You have to step back a little bit every now and then and recognize that the technology that we’re working with—cell therapy, gene therapy, gene editing—is pretty disruptive for a lot of these stakeholders. It brings tremendous hope and promise, but it also brings some challenges and questions along the way,” he suggests.
Ebony Dashiell-Aje (Global Forum): It’s my pleasure to talk with you today about the current and future states of the cell and gene therapy industry, Tim. The alliance recently held its annual cell and gene therapy “State of the Industry” public briefing, and we want to ask about your 2025 forecast: What key areas need attention to drive the field forward in 2025?
Timothy Hunt (TH): We want to continue to see a modernization of the payer landscape for cell and gene therapy. The Alliance for Regenerative Medicine includes biotech companies, pharmaceutical companies, patient organizations, some leading academic centers, and a lot of tool and strategic service providers. But we’re very modality focused: We focus on cell therapy, gene therapy, gene editing, and a little bit of tissue engineering. That’s our real focus within this community.
A lot of our push over the past few years, and probably for the foreseeable future, is: How do we think about continuing to modernize the payer systems, in particular in the US and in Europe? And then, how do we think about a similar continued evolution with regulators in the US and Europe? Our focus on Asia is increasing, but our membership primarily comes out of the US and Europe.
GF: What aspects of modernization are most important for payers, starting with the US and then the EU?
TH: In the US, about half the patients who will take a gene therapy or gene editing medicine are Medicaid patients. So, a big focal point for us is: Do Medicaid patients get timely access to these often lifesaving or life-improving therapies? If you’re a patient that is going to reach for a gene therapy or gene editing medicine, or a cell therapy, you’re probably in pretty rough shape. The average life expectancy for diseases that have an approved gene therapy in the US is about half the life expectancy—early to mid-40s—of a typical person. These are very powerful medicines. We want to make sure that patients get timely access to them and do not encounter delays from prior authorization requirements and other things.
We’re very pleased that the CMS Innovation Center, the innovation office within the US Centers for Medicare and Medicaid Services (CMS), put together a gene therapy access model using sickle cell as sort of its first test case, and both of the FDA-approved sickle cell therapies are part of this access model. CMS just announced that 35 states will participate in the model. We think it’s a good glimpse of the future because it’s the Administration embracing both gene therapies and things like value-based payments, which are very important.
These gene therapies are typically somewhat expensive, in the range of two to three, even upwards of $4 million, and we think that there’s a great future in looking at these therapies and saying: “If they work well, then you should pay for them based on the value they create; if they don’t work, some percentage of those costs would be borne by the biotech or pharmaceutical company that’s developing them.” This cell and gene therapy access model is a way to drive that framework through the Medicaid population and aggregate many state Medicaid programs into one pool, where CMS will centrally manage these value-based agreements. We think it’s a great efficiency tool.
Update and access in the EU has been challenging, but things are much better than they looked three years ago. As is often the case, there’s a lot of worry when the theoretical is coming: We have a gene therapy coming; how are we going to pay for it? One forcing function is having approved therapies that work very well, and so health technology assessment bodies now have to make actual decisions that will impact the actual lives of often very sick patients. We’re seeing that they’re sort of working through these things company by company in various countries, and by and large it’s going better than we thought three years ago.
There is a big push out of the European Commission for their joint clinical assessment (JCA) project, to look at a joint, EU-wide mini health technology assessment during the EMA approval process. That project began in January 2025, and we’ve been working with the European Commission and others to ensure that the methodologies in place do not disfavor, or do not put downward pressure on, single-arm trials, which would be very tricky. Curiously, some countries struggle with single-arm trials and really want double-blind, randomized placebo-controlled trials, which are of course unethical to run for many rare and ultrarare conditions. We’ve been working to ensure that this process is on the rails and fit for purpose, given our patient population.
GF: Could you also talk about how the evolving regulatory environment might provide an upstream push for adoption of cell and gene therapy?
TH: We’re talking just a few days after the news that Peter Marks is leaving the FDA. It’s worth noting what a seminal figure he has been for the cell and gene therapy community. He is a visionary mind and has been a very strong leader within our community, and he’ll certainly be missed. We are very pleased, however, with the excellent team in place at the FDA Office of Therapeutic Products (OTP) and have a lot of confidence in that organization. They’ve modernized and transformed that group over the past 18 months and are an equal partner with the EMA on a lot of important regulatory science frameworks.
GF: We’ve seen a lot of progress with a number of key stakeholders—payers, regulators, and others—sort of catching up. People in the community seem more open to the specific innovation that cell and gene therapy can bring to transformative medicines and therapies for patients who need them most. But there’s always the “rumor on the street” that sponsors aren’t committed anymore or not as committed as we thought they would be when this technology became “the buzz.” What myths must we overcome to keep progress moving?
TH: One that certainly comes to mind is the question that has emerged over the past year about the commercial future of some of these products. You hear it every now and then, and some of that, as is often the case, is grounded in a touch of reality. If you’re looking at an ultrarare disorder, it IS tricky to think through the commercial potential if you’ve only got 1000 or maybe a few thousand patients. Similarly, some people thought that the hemophilia or sickle cell markets might deliver bigger products or that those launches would be faster and more aggressive. I think that’s fair to a point.
Some of these are very real markets that are going to take a little bit of time to develop. But there’s a market there. It’s just going to take some time to unlock it. Some will be meaningful products, and some will eventually or potentially be eclipsed by second- or third-generation technologies over the next five to 10 years.
The ultrarare model is a bit challenging if you’re only going to see the patient once as opposed to chronic dosing. But companies still make decisions every day to be in the ultrarare space in cell and gene therapy. Sometimes they do it because they think they can aggregate patient populations. With platform technologies, they can run a number of trials, typically gene editing trials, where they can aggregate more patient populations, or they can align a trial with the FDA, the EMA, and maybe the MHRA and have more patients that way.
Sometimes it’s a strategic play in the ultrarare space. We see a lot of that. It’s very common for a company to want to prove out their technology where there’s clear unmet need. They understand that there’s not a huge patient population representing a large commercial opportunity, but they want to prove that their team can file an IND (Investigational New Drug application), can run the clinical trials, can manufacture the product, and eventually get it approved and launched, whether it’s in the US or Europe or other geographies. That important strategic view of ultrarare disorders is not going away anytime soon.
There’s some great potential coming. One of our partners helped us evaluate some Wall Street consensus data. There are already two CGT blockbuster products, and the Wall Street analysts’ consensus data predicted that there will be two more this year (2025). This year alone, we’ll double from two to four. By the end of 2030, that number will grow to 10 blockbuster products.
That’s pretty good growth in a very compressed time. The Wall Street consensus data also points to a total of 30 products, the 10 blockbusters plus another 20, that would each have somewhere above $500 million in annual sales by 2030. I’ve been in biotech for a number of years. If you’ve got a $500 million, $700 million, $900 million product, that’s a real biotech product, and lots of companies would be really glad to have it.
And that’s one of the reasons—and this gets to a second myth—why large pharmaceutical companies are investing heavily in cell and gene therapy. Another myth you hear every now and then is that large companies aren’t that interested in it. That sounds weird to me because a lot of these companies are either on or they’re trying to get on the ARM board of directors, and they’re either members or we’re chasing them to become members of ARM.
I did the math on this one: 15 of the top 20, or 75%, of the largest pharmaceutical companies by market cap are actively involved in cell and gene therapy. They’re big companies like Lilly and Novo Nordisk and Johnson & Johnson and BMS, and they’re investing in areas like CAR-T therapy or they’re taking long bets on cell and gene therapy and gene editing. Eli Lilly just opened up a big new office focused on gene therapy and gene editing right in the Boston seaport. These companies are also looking down the road at things like cell therapy in autoimmune disorders, cell therapy in solid tumors, and gene therapies in more prevalent conditions. There is significant potential in these areas, and these investments by the larger biopharmaceutical companies are pretty clear.
GF: What is your projection for 2025?
TH: We saw a couple of deals to close out 2024: Poseida Therapeutics was acquired by Roche and Kate Therapeutics was acquired by Novartis. I think there is greater optimism that the incoming Federal Trade Commission will be more permissive for those combinations. Whether it’s large companies merging or smaller companies being acquired, they can move through deals more smoothly and we think that’s likely going to heat up. The capital markets have been cool for all biotech for the past three-plus years. Nobody thinks that there’s just going to be this magical restart when capital will come and IPOs will restart. People are hopeful that things will warm up. Certainly, the science is superb in the cell and gene therapy space. We just want to see the financing occur there as well.
GF: One last myth to address is that regulators, industry, and payers are buying in, but the global scale is not quite there yet. Is that true and how do we overcome that challenge?
TH: These are transformative products, but at this stage of the technological development they also can be expensive to make, and we are in the early days of global access for CGTs. We think the cost of goods will come down as these products scale up. A lot of work has been done to drive down the cost of goods, but there’s still work to be done. These are expensive therapies to make, and some of the dosing regimens for patients are complex. But then you see products like Novartis’ treatment for SMA, in more than 50 markets around the world, including very atypical markets such as Brazil and Ecuador and Egypt, which is great news for patients. A lot of patients have access to one of the original blockbuster products in this space, and you see examples of other products that are similarly situated.
It’s really hard to do that if you’re a small biotech company. We saw Bluebird’s experience with putting value-based frameworks together in places like Germany years ago. It was what I think of as the “pioneer tax”: You’re first out of the chute in trying to do something incredibly hard. You’re driving multiple things that are new and different, and the change is hard. It’s certainly hard if you’re a relatively small company. The global access issue has been furthered quite a bit by some of the larger companies I mentioned. I think we’re going to continue to see greater global access and partnerships, whether it leads to mergers or acquisitions or partnerships where people realize that they need help commercializing their product across the globe.
GF: What can we do to help dispel these and other myths?
TH: There’s that great line by Mark Twain: “A lie can travel halfway around the world while the truth is still putting on its shoes.” The first way to dispel a myth is to just talk about it. If there’s an elephant in the room, it’s best to just address it. We’ve tried to do that here today.
The second thing is to really deliver and execute. As companies have more and more success, these successes become forcing functions. Biotech has always required a great deal of courage and grit to approach a regulator with an IND, to launch a commercial product, to approach an HTA body and hammer out an agreement that helps patients. Courage and grit are part and parcel with this field. This is hard work. You have to realize and get after that.
And then the key final thing will be to make sure that we always keep patients as our North Star.
GF: Please preview your upcoming ARM project on ethics in cell and gene therapy.
TH: Some of this goes back to my previous industry experience when I was talking to different stakeholders from patient organizations to policy leaders to regulators to payers and others in the field, and some of this work was done in my first year at ARM.
You have to step back a little bit every now and then and recognize that the technology that we’re working with—cell therapy, gene therapy, gene editing—is pretty disruptive for a lot of these stakeholders. It brings tremendous hope and promise, but it also brings some challenges and questions along the way.
I get asked all the time why these gene therapies are priced the way they are. It is not lost on people that 80% of the world’s sickle cell patient population is not in the US or Europe; it’s in India and a small number of African countries. The market is actually somewhat concentrated, just not in the US and Europe. What about the commercial model for ultrarare disorders? Bioethical questions come up from time to time. We will continue grappling with some of these thorny issues for the next few years.
So, we kicked off our Cell and Gene Therapy Ethics in Society initiative. It’s got four pillars. Number one: How do we communicate about pricing and value with these cell and gene therapies? That’s the first one, and it was clearly on people’s minds back in 2023 as products were starting to launch and as more products were launched in 2024. As I mentioned, people are working through commercial models in real time in the US and Europe, and so there’s a little bit less concern here.
The second pillar is around industrialization of the field and how it can enable global access. As we get the cost of goods down, as second- and third-generation technologies come that might present easier dosing regimens for patients, maybe more in vivo therapies, how does all that combine into what we call industrialization of the field and enable global access?
The third pillar is the unique combined challenge of the ultrarare disease space and the cell and gene therapy commercialization model. Seeing the patient only once does pose real challenges. We think there’s sort of an “all of the above” approach to solve some of these problems: Solutions could come from for-profit companies, some nonprofits, some will probably come out of academic institutions, some could involve perpetual INDs, depending on how many patients you’re looking to see.
The last pillar is kind of the more traditional bioethical things around guardrails for the most “frontier” kinds of technology. The one that always comes to mind from the gene editing space is heritable human genome editing, or germline editing: editing an embryo to try to make a permanent change into a future human being, not treating patients who are walking around with a disorder today. It’s out in the future, but it gets a lot of attention from some media, academia, and others. That’s a problematic area.
GF: How can we refine the perception of gene editing and recreate the narrative around its promise, while guaranteeing the necessary guardrails?
TH: The first topic is gene editing writ large: CRISPR, prime editing, base editing, and epigenetic editing. This was certainly an incredibly hot field for a number of years, and the science is developing further along. This is a very promising area. The markets are what they are, but I would argue that they have been irrational in their reaction to this technology. Gene editing has an incredibly bright future. Products in development now are breathtaking in what they can do. This has been an overcorrection without question, and the future looks incredibly bright.
More communication is helpful. Proving out the technology in the real, commercial world will help quite a bit. There’s a bigger push now for in vivo editing, and we see companies making good progress in that area. Then these “next generation technologies” mentioned above are also very impressive. This area will continue to evolve very nicely with the science. Regulators are much more comfortable with some of the technology, certainly with in vivo editing, than they were a few years ago, so there’s a very bright future there. That’s all somatic cell editing, which everybody acknowledges is highly ethical and important for patients and has generated real, approved products.
Then there’s this very different and very speculative world of human heritable germline editing, the purview of the infamous “designer babies” that were announced in China back in 2018. We recently conducted a conference with the American Society of Gene & Cell Therapy (ASGCT) and their international counterpart the International Society for Cell & Gene Therapy (ISCT) on this topic and heard many views from scientific experts, religious leaders, and patients. There are vanishingly few use cases where this could actually be applied, even in the years ahead. I don’t think anybody thinks that this technology is ready for human clinical trials anytime soon. That is MANY years away and there are still real questions like: How would you develop an assay? How would you measure safety? How would you do governance? Where does human health end and you begin to slide into areas like enhancement? There are so many more questions than answers at this point. There have been calls for global moratoriums, and I think that’s probably where this should land for now. It’s not ready.
GF: How will different partnerships and collaborations continue to help push this science and these products forward, while ensuring that their future is not put at risk by missteps like this?
TH: A broader coalition of interest groups is looking at and concluding a few things about this issue. Somatic cell editing is really important and, just like somatic cell editing, gene therapy is very important. Cell therapy is really important. These can potentially transform the lives of patients who are very difficult to treat. But germline editing is very far into the future and speculative. The Global Observatory for Genome Editing, another very good organization, has done extensive work in these areas. Locking arms with regulators, public policy leaders, patient organizations, biotech companies, and others on this topic is very important, and most experts agree that this ought to be in a box that should not be opened, at least for now, and that our energies are best placed by focusing on advancing somatic cell editing.
GF: We talked earlier about the global commercialization and pricing dilemma. What about the impact of recent geopolitical changes on the policy landscape and other aspects of cell and gene therapy?
TH: If you roll back the clock 12 months, it was probably an underappreciated topic. We’ve seen changes in governments in the US, in the UK, in Canada, changes in Germany and in France, South Korea; a lot of change has taken place in some very important markets around the world. There’s a lot of disruption, and change does grab a lot of headlines and rightly so.
But there are also enormous opportunities that people need to keep a clear eye on. When there’s all this disruption and change, people tend to focus on playing defense, and it’s really important to also think about how you play offense. This technology is disruptive, and people may have legitimate questions about it. They may understand the technology and still be nervous about it. It’s human nature. So, we need to communicate with everybody on the right, on the left, and in the center. It’s incumbent on us to spend time talking to people about what the technology is and what the technology is not. Explain that and then meet people where they are and ask them what their hopes and concerns are. This can be a very powerful solution.
I’ve also had the opportunity to spend some time with people inside the US government who have expressed a real commitment to ensuring that the US remains a global leader, if not THE global leader, in this space. When people see the transformative impact that this technology can have on patients, they are instinctively drawn toward it. They may have some legitimate concerns about how we as a society can afford these innovations down the road. But they also see the promise, which is terrific.
GF: How will this impact potential adoption in other developed economies?
TH: As I mentioned, I’m a big fan of the leadership team at OTP, and the work that they’ve done in the past 18 to 24 months has been notable. I hear about it from within our community all the time. It was not that long ago in the gene editing space that companies would say: “I’m not going to start my first trials in the US. I’ll start them in New Zealand. I’ll start them in the UK. I’ll take them elsewhere.” Why? Because they weren’t convinced that FDA would handle the technology appropriately. They didn’t necessarily understand it. There wasn’t a “meeting of the minds” on it. And that has changed for the better.
FDA has also put out notification that they want to develop guidance this year on gene editing as a platform. This topic has been discussed for about a decade. It would be terrific to have that kind of guidance. But they’re not alone. We’ve talked to the EMA about this; they’re interested in it as well. People see the technology, they want to embrace the technology, and they want the technology to be successful. And the US is not alone: Europeans want to advance the technology. Lots of markets across Asia, from China to Japan to South Korea and others, are taking a strong look at this. But if regulators and payers stand still or slow down, they run the risk of being eclipsed.
GF: How do you view the role of broader regulatory groups such as the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) in helping to drive more harmonized guidance and assessment between independent organizations such as FDA, EMA, MHRA, etc.?
TH: I’m a proponent of “all of the above,” and I think they all have a role here. Harmonization is difficult. Oftentimes, there is lots of talk and discussion and less action. Our view is that collaboration and coordination before the fact is likely easier than harmonization after the fact.
Using the gene editing platform as an example, nothing exists right now, so this would be an ideal time for the FDA and the EMA and the MHRA and others to look at what would make the most sense to put in place. If you can get one IND cleared, how can you reference that work so that you could add an indication, then another indication? When we talk about industrialization of the field, this is a glimpse into exactly that. Instead of one or two thousand patients, biotech companies could aggregate seven to ten thousand patients if they could work in a few new indications and across multiple geographies. This might more efficiently unlock cures for more rare diseases, which would be fantastic for the patient communities. We think that’s an area to push on before any guidances are set and locked in stone: Can you coordinate and harmonize ahead of time?
GF: To close, please share your thoughts and hopes for the future of these cell and gene therapies.
TH: The fields of cell therapy, gene therapy, and gene editing have an incredibly bright future. There have been some headwinds, and I don’t doubt there will continue to be headwinds in the future. Certainly, the financial markets have been difficult for the past three years, and we’re going through some significant policy bumps in the road right now in the US and other geographies. But the future is incredibly bright, and we can’t forget that the important ingredients of courage and grit are really part and parcel of biotechnology. Great technology is wonderful, but a lot of sweat equity goes into building these companies and markets and building this technology out. And the best guidance we can have is to keep patients as our North Star.