Cancer treatment has made remarkable strides in recent years, driven by significant advancements in the field of biologics and advanced therapies. The latest trends in oncology emphasize the importance of immune cell therapies, which are revolutionizing how we approach cancer treatment. Unlike traditional methods such as chemotherapy and radiation, immune cell therapies offer a highly targeted approach, enhancing the clinical benefit over the risk and improving quality of life for patients. These therapies, which harness the body’s own natural defenses to combat cancer, also provide the potential for more enduring treatments that confer less toxicity to patients.
The power of immune cell therapies lies in their personalized nature. These drugs, often manufactured using a patient’s own cells, are produced in single batches and require skilled handling, highly technical manufacturing, and careful transport to ensure their safety and efficacy. CAR-T cell therapy demands similar efforts, along with additional technology for genetic modification. Consequently, significant cost challenges arise, particularly for patients. For the six CAR-T therapies currently approved by the FDA, the average listed price is approximately half a million dollars for a single dose.
This comparatively high cost is attributable to the highly bespoke nature of immune cell therapy production. The intricate process of manufacturing immune cell therapies involves a complex series of steps, including cell collection, isolation, expansion, and in the case of CAR-T therapies, modification. Each step demands rigorous quality control, specialized equipment, and highly skilled personnel; moreover, the limited scalability of these processes contributes to higher production costs compared to traditional therapies. Additionally, the highly manual processes requiring significant Full-Time Equivalents (FTEs) and stringent quality controls further escalate the costs.
Ultimately, the cost of producing these drugs comes down to a few core considerations:
Autologous Origin: Unlike allogeneic therapies, which can be administered to multiple patients from a single source, autologous therapies are administered only to the individual from whom the cells were derived. This results in relatively higher manufacturing costs.
Complex Manufacturing Process: The extraction of a patient's immune cells, their subsequent cultivation, and the intricate genetic modifications undertaken prior to reinfusion represent a sophisticated and resource-intensive methodology. Despite concerted efforts to streamline these processes, the average "vein-to-vein" time remains in excess of three weeks. This duration includes numerous critical steps and requires significant labor input, underscoring the complexity and cost associated with it.
Technology and Modality: Culturing, genetic modification, and targeting technologies are key to overcoming the limitations of conventional cancer treatments, making these technologies highly valuable. Consequently, the modalities incorporating these technologies are expensive.
Raw Material Costs: The high costs of biological raw materials required for cell therapy manufacturing, such as high-quality media components, growth factors, and viral vectors, contribute to their overall expense.
Logistics and Supply Chain Management: Cell therapies must be stored in refrigerated or frozen conditions, increasing logistics costs. Additionally, personalized therapies require rapid supply chain management, incurring additional expenses.
As interest in anti-cancer immune cell therapies grows worldwide, many bioprocessing companies are pursuing wide-ranging efforts to improve the high cost of approved CAR-T cell or tumor-infiltrating lymphocyte (TIL) therapies. As a result, new and innovative immune cell therapies are being developed that will significantly improve the cost of goods sold (COGS) during production, providing patients with access to highly effective treatments at a more affordable price.
Recent Advancements and Investments
To address these cost challenges, the industry is increasingly turning to automation to streamline production processes. In the manufacturing of allogeneic cell therapies, automation reduces dependency on manual labor, thereby lowering labor costs, and enhances precision and consistency in production. By incorporating concurrent quality control (QC) measures into automated systems, real-time monitoring and immediate correction of deviations are possible, further driving down costs and improving efficiency.
However, for autologous cell therapy manufacturing, significant efforts are being made to incorporate automation. Despite these efforts, the high maintenance costs associated with automation—such as for machines, programs, and disposable kits, along with the relatively small scale of production for each patient—pose substantial challenges. Consequently, sticking to traditional manufacturing processes remains the only viable method to provide affordable therapies to patients.
Moreover, significant investments are fueling the development of advanced next-generation CAR platforms, each with distinct benefits. Novartis' T-Charge platform is specifically designed to reduce the turnaround time for ex-vivo CAR-T therapies, aiming to expedite treatment delivery. Concurrently, new initiatives like Umoja's and Interius' pioneering in vivo CAR-T therapies seek to eliminate the ex-vivo expansion step altogether. Although these in vivo approaches are in their early stages, with clinical studies just beginning, they hold the potential to significantly streamline the CAR-T therapy process. These innovations aim not only to enhance the efficacy and safety of CAR-T therapies but also to reduce production costs, thereby broadening access to these life-saving treatments for a larger patient population.
The Current Landscape: Understanding COGS For Immune Cell Therapies
Cancer threatens the health and well-being of patients worldwide regardless of economic status. As such, finding avenues for increasing production efficiency, optimizing manufacturing processes, and identifying economical alternatives for raw materials without compromising quality have all become paramount for the clinical research space.
Of the six CAR-T therapies currently approved by the FDA to treat blood cancer — Kymriah, Yescarta, Breyanzi, Abecma, Tecartus, and Carvykti — all are produced autologously. Additionally, Amtagvi, which was recently approved by the FDA as the first treatment for solid tumors, is also produced autologously from isolated and cultured TILs and costs roughly $515,000, excluding rebates or discounts.
The highly manual and small-scale nature of autologous therapy production and the resultant cost burden has led many to pursue an alternative in the form of allogeneic manufacturing. In contrast to autologous production, these approaches enable the use of healthy donor cells to treat multiple patients. Although mass production of immune cell therapies is more feasible using an allogeneic approach, other challenges have served to limit its viability in the near-term. These include an increased incidence of immunological side effects such as graft-versus-host disease or immune rejection, along with the concerns that typify cell therapy production generally — namely, the difficulty in achieving consistent and scalable production while maintaining cell quality.
At present, the superior safety profile possible with autologous production techniques has cemented their position as the preferred development avenue for immune cell therapies. A significant amount of resource investment is required to produce these drugs, including costs for culture media, reagents, consumables, GMP facility management, labor, and shipping. As such, efforts to control these costs—whether through focusing on logistical considerations like sample collection and dosing schedules or optimizing the manufacturing process efficiently—have paved the way for more affordable therapies such as ImmunoACT’s NexCAR19, an autologous CAR-T therapy, and GC Cell’s Immuncell-LC, an autologous CIK (Cytokine Induced Killer) T cell therapy.
The Future of Affordable Autologous Therapies
A notable advancement in the field of autologous immune cell therapies comes from ImmunoACT, an Indian biotech company, with their NexCAR19 product. NexCAR19, a humanized CD19 scFv and second-generation CAR-T cell therapy to treat relapsed/refractory B cell malignancies, has demonstrated an effective overall response rate (ORR) of 67% (36/53 patients), a complete response rate (CR) of 52% (29/53 patients), and a favorable safety profile in ASH 2023. It is currently in an ongoing phase II trial and has received market authorization by regulatory authorities of India.
ImmunoACT aims to provide a more affordable and accessible treatment option for patients. By leveraging advanced manufacturing techniques and cost-efficient processes, ImmunoACT has been able to significantly reduce the production costs of NexCAR19 without compromising on efficacy. This approach has made NexCAR19 a promising and affordable option for patients requiring CAR-T therapy, particularly in regions with limited healthcare budgets.
GC Cell's Immuncell-LC, an autologous anti-cancer CIK T immune cell therapy, exemplifies cost-effective innovation within the oncology sector. Approved in the Republic of Korea, Immuncell-LC serves as the sole adoptive T-cell adjuvant therapy for the prevention of recurrence following surgical treatment of early-stage hepatocellular carcinoma (HCC). With a total of 16 doses, Immuncell-LC has demonstrated substantial clinical advantages and is more affordable than other CAR-T therapies in global markets. In a large-scale Phase 3 clinical trial, it showed a 37% reduction in the risk of recurrence and a 79% decrease in mortality risk, thereby earning international acclaim for its effectiveness and value.
Both NexCAR19 and Immuncell-LC represent significant strides in making autologous immune cell therapies more affordable and accessible. These therapies represent how innovative approaches in production and cost management can lead to effective cancer treatments that are within reach for a broader patient population.
Conclusion
The significant challenges associated with immune cell therapies have not deterred the ongoing research and development aimed at refining production processes and reducing costs. It is essential to overcome these barriers through enhanced technology, improved process engineering, and more efficient supply chain management. Currently, the emphasis is on autologous therapies, yet the exploration into allogeneic approaches, known for their scalability, is gaining momentum. As this field progresses, it is crucial to ensure a balance between making immune cell therapies accessible and affordable, and upholding rigorous quality and safety standards. Continued research and innovation are key to transcending the existing limitations of this field and broadening the availability of effective, economical treatments for patients.
