Can cell and gene therapy revolutionize the rules of healthcare?

At BIO-Europe 2024, Romain Bonnot, principal at ZS, hosted a lively and interactive session on commercializing cell and gene therapy (C&GT), with Celine Carlet, VP head of transactions at Belgium’s Galapagos, Michael May, president and CEO at Canada’s CCRM and Reagan Jarvis, CEO and scientific founder at Sweden’s Anocca. The panelists addressed a wide range of audience questions about how these innovative modalities could push the boundaries of medicine, as well as about the challenges around financing, manufacturing, scaling and optimizing these complex technologies for use as sophisticated, personalized products.

An active and growing field

The field is highly active and focused on conditions where there is a high unmet medical need. Revolutionary science like TCR-T-cell therapies can redefine the treatment of some of the most challenging types of cancer. A product derived from living human cells is revolutionary right from its conception and something quite distinct from, say, a small molecule pill. The belief of regulatory agencies in the sector has also encouraged the field’s growth through the development of supportive regulatory frameworks.

C&GT is changing the way products are developed by looking to understand the detailed molecular biology of a disease and the corresponding treatment approaches. An example is Adaptimmune’s cell therapy work, which restarted innovation in soft tissue sarcomas, a high mortality disease where there had been no significant advances in 40 years. In 2024, the company received approval for the world’s first TCR product in sarcomas.

Personalized medicine, which cell therapies often are, means not giving something to a patient that won’t “fit.” By knowing so much more about molecular biology and exactly how a tumor is working, it should become routine to screen for patients who will respond to a therapy and to design efficient clinical trials with specific inclusion and exclusion criteria. And who wants to give a patient a therapy that doesn’t work for them anyway?

This plays well in improving the probability of technical and regulatory success (PTRS). Taking a PTRS approach also significantly reduces trial costs, which are a major factor in the calculations of net present value (NPV) over the product lifetime for C&GT. The costs of labor (across quality, engineering and manufacturing) and viral vector manufacturing are the main components, as detailed in the image below.

A wider societal benefit is patient coverage. Therapies that companies such as Anocca are developing address the broad diversity of the same disease at a molecular and genetic level through targeting multiple HLA haplotypes. The intent is that there should be a therapy that works just as well for a young woman with an Asian heritage as it does for a senior white man in the United States. These benefits stretch beyond helping patients, as there are economic development benefits of becoming a leader in a pioneering treatment modality, such as jobs and investment into cell therapy hot spots like the Nordics.

Pushing at the frontiers of science

But this is biotech, and when you push at the frontiers, the frontiers can push back. The key challenges in the field are in R&D and manufacturing, especially scalability. C&GT products require greater investment up front to make than traditional small molecule modalities. C&GT is addressing high-value therapeutic areas, including in oncology, neurology and immunology, where there is significant patient burden.

As well as complex manufacturing, timelines for autologous cell and gene therapies that are readministered from the patient’s own cells are more critical than for conventional treatment modalities. From a logistics standpoint, companies are making smart choices to address this accordingly. For example, Galapagos has a decentralized cell therapy manufacturing model, meaning manufacturing can be geographically close to the patient, enabling rapid delivery of fresh autologous cells. Galapagos also has clinical trial sites across Europe, and, on the back of its first IND, is building its U.S. network to offer wider access to cell therapies. This decentralized manufacturing approach shows a potential for developing cell therapies with enhanced properties, and there is emerging clinical data showing that it is possible to achieve a deeper and longer anti-tumor response.

Geographic reach, especially for European companies looking to offer their valuable products to a U.S. market, can be secured through partnerships with highly respected companies there, such as Thermo Fisher Scientific, which is fundamental to making cell therapies widely available.

Galapagos’ recently announced strategic collaboration with Blood Centers of America,  to scale up decentralized manufacturing, harmonize operation and  access apheresis capacity, is another example. 

New approaches to simplify manufacturing through allogeneic, off-the-shelf cell therapies will pave the way for making this approach more reproducible, standardized and scalable. And this, in turn, will bring down manufacturing costs. The focus for autologous cell therapies is also on being standardized and reproducible, but allogeneic approaches can improve the yield challenge with autologous patient cells, given the poor fitness of donors.

The pharmacy of the future

Nothing worthwhile is ever easy, and these clever new approaches can raise their own challenges. But we’ve heard this story before. Transplanting a heart, a living product, was once seen as impossible. Yet now, in the U.S. there are approximately 3,700 heart transplants a year. The world has clearly come a long way since the first transplant done on 3 December 1967 at Groote Schuur Hospital in Cape Town, South Africa by pioneering surgeon Dr. Christiaan Barnard. What was unimaginable in the early 1960s, is quite unremarkable today. “It always seems impossible until it’s done,” as South Africa’s Nelson Mandela wisely said. With all the technological advances in using living products we have had since before humanity’s first step on the moon, is it too giant a leap of imagination to see the pharmacy of the future routinely dispensing prescriptions for C&GT products?

Organizations everywhere are investing to make that future happen. As American-Canadian science fiction author William Gibson said, “The future is already here, it’s just not evenly distributed yet.” The future is closer in Sweden. At Anocca, based just outside Stockholm with its team of more than 120 that includes scientists, technicians and developers, the company is working on the engineering and logistical solutions to improve yields in centralized manufacturing for clinical trials. Anocca has the largest cGMP facility in the Nordics. The company’s longer-term strategy for product development encompasses gene editing and allogeneic approaches with the goal of creating off-the-shelf products that provide a step change in scaling manufacturing and reducing the overall cost of goods. In cell therapy, collaboration is key to achieving these technological advances. Anocca has partnered with EmendoBio in non-viral gene editing to achieve simpler manufacturing. The company also collaborates with Shinobi Therapeutics with the long-term goal of moving to off-the-shelf allogeneic manufacturing.

So, what does the future hold? C&GT in 2029 might encompass a mix of approaches, with a proportion of cell therapies made in a big, centralized facility, taking advantage of supply chain and logistics practicalities to serve large population centers. Decentralized manufacturing, close to specialist care centers, will become essential for autologous delivery. It is linked to point-of-administration manufacturing and requires making the therapy close to the patients while reaching them earlier, a feature critically important for fast processing of life-threatening diseases such as cancer. Allogeneic delivery could further support these requirements and make cell therapies even more broadly accessible to patients.

Addressing future affordability

Gene therapies, which generally tend to be related to rare diseases or corrections of in-born genetic errors, have simpler viral manufacturing approaches. They do not require the volumes needed for treating common diseases. The challenge here is getting the manufacturing done consistently. Sometimes you need to take one step back to move a few forward. Think about Sarepta Therapeutics, who have been incredibly successful in moving the whole field forward but have recently had a failure with one of its exon-skipping variants for treating Duchenne muscular dystrophy (DMD).

“Affordability” is often the difficult word that crops up when discussing C&GT, as “one and done” gene therapies, such as for DMD, are understandably expensive. However, this is on a per-patient basis: They tend to have little or no impact on national healthcare systems, as only a few patients are treated. By contrast, about 45 million people in the U.S. are on statins, which cost over $10 billion a year. And, with everyone everywhere talking about GLP-1s and the number of people benefiting from this class of drugs growing as it is being developed for multiple indications, these budgets will dwarf what is needed for C&GT. In the production of biologics, a major cost is the plastics used for aseptic work. And as volumes increase, prices will fall, just as they do with any other products. Affordability will ultimately be a challenge for payers to solve, but, globally, we are heading toward a fair share of private insurance, out-of-pocket and even employer-funded solutions.

Putting C&GT modalities in context

Cell therapy can’t cure everything and won’t be the right modality for everyone. Access, regulatory and pricing authorities all exist to make considered decisions about access and who receives what, as well as about setting the price. Notably, cell therapies, including CAR-T, are currently often the “therapy of last resort” when patients have exhausted all other (cheaper) options. Therefore, they provide the only glimmer of hope on the horizon. This is a major reason why these therapies have been developed in the first place: What’s currently available simply isn’t good enough to keep patients alive for long, especially when they have advanced solid tumors. The commercial opportunity is then built around unmet medical need, and the data generated in well-designed trials shows that a modality has transformative potential compared to the standard of care. An example would be a patient who has diabetes never needing insulin again due to a successful islet cell transplant.

C&GT modalities need to be seen in context to have a clear picture of the value they bring, with value meaning different things to different stakeholders including better patient outcomes and better economics for healthcare systems. Overall, as Romain highlighted in his personal view, health systems tend to optimize at the top of the innovation life cycle. That is, they tend to increase pressure on price but remain relatively inflexible on potential endpoints, such as surrogates and proxies. This de-incentivizes innovation in these aspects. A better approach would be to increase the pressure at the end of the innovation cycle. For example, they could do this by working jointly on a reasonable patent lifetime and patent extension strategy, as well as by finding new ways to capture superior efficacy into pricing. This should drive an increased willingness to invest in innovation to catch the “pricing and access” wave.

As cell therapies move beyond oncology into therapeutic areas such as autoimmunity, the biology becomes even more complex. Fortunately, a bit like landing on the moon, deeper exploration of the unknown has helped make it more accessible. In the same way oncology cell therapies provide the tools to enable bold ventures into other areas, they fuel the evolution to move beyond oncology. Ultimately, reducing complexity in product development and manufacturing and improving scalability through decentralized manufacturing, gene editing and off-the-shelf allogeneic approaches will be transformational for this field, as it has the potential to enable life-changing treatments for more patients who currently have no other treatment options.