What Global Survey Says About Scant Patient Access To CAR-T Therapy

By Eddie H.P. Tan, Centre of Regulatory Excellence, Duke-NUS Medical School, National University of Singapore

Despite the revolutionary effectiveness of CAR T cell therapy in treating B-cell malignancies and seven approved products on the U.S. market — more in other markets — access to treatments remains a critical issue globally.

The price of approved CAR-T products currently ranges between $300,000 and $500,000 per treatment. The manufacturing process involves genetic engineering of a patient's T cells to express chimeric antigen receptors targeting specific cancer antigens. The traditional centralized manufacturing model poses challenges for global access, creating increasing interest in decentralized approaches, including point-of-care production. Academic institutions are playing a key role in expanding manufacturing capabilities. There is growing evidence for efficacy beyond initial indications, with expanding applications to multiple myeloma and solid tumors.

To understand the global CAR T cell therapy landscape, the Worldwide Network for Blood and Marrow Transplantation (WBMT) initiated a comprehensive cross-sectional survey to assess global CAR-T availability.¹ The survey findings highlighted global disparities in CAR-T access, identifying critical factors affecting access such as cost, infrastructure requirements, and regulatory frameworks. It is essential to fully understand and discuss these challenges to better devise strategies that will improve global therapy availability.

Survey And Key Insights

Survey methodology and scope

The survey was an online cross-sectional study conducted with UT Health San Antonio. Participating centers were invited via email through supporting academic societies to report data in 2023. The survey was available for a period of three months and included 55 queries on various topics. The topics included demographics, CAR-T availability, manufacturing capabilities, apheresis, accreditation, reimbursement, regulatory frameworks, and legal oversight.

A total of 181 qualified responses were collected from the survey. The survey gathered responses across North America, Asia, Europe, South/Central America, Australia/New Zealand, and Africa. It was noted that most respondents were from academic teaching hospitals, a possible bias introduced by the mode of survey invitation.

Availability and awareness of CAR-T therapy

Out of 180 centers surveyed, 140 reported the availability of CAR-T therapy. Availability is notably high in North America, with 85 out of 91 centers offering CAR-T, while regions in the Global South exhibit lower accessibility. Approximately 57% of centers currently without CAR-T therapy plan to introduce it within the next five years. Respondents identified several barriers to implementation, including cost, support, governmental challenges, and infrastructure limitations. Additional obstacles noted include the distance to therapy and political instability.

A total of 162 out of 179 centers reported having hematopoietic stem cell transplantation (HSCT) programs. Most of the respondents also indicated that the availability of CAR-T therapy is closely linked to the existence of HSCT programs. This highlights a potential role for existing HSCT infrastructure in facilitating CAR-T therapy availability.

Most noncommercial CAR-T products are employed in clinical trials, with many of these products mainly manufactured by other centers or produced in-house in compliance with GMP.

Reimbursement

Unsurprisingly, the survey highlights the significant costs associated with commercial CAR-T therapies. This is in line with the reported cost and reimbursement trends for approved CAR T cell therapies so far. However, this high expense inevitably acts as a major barrier to access for many patients and healthcare systems.

Noncommercial CAR-T therapies, on the other hand, often have their costs covered by trial sponsors, with out-of-pocket estimates ranging from $40,000 to $180,000. However, detailed information on these figures is scarce. The reimbursement landscape is more complex in regions like Asia and South America, where funding sources include government support, self-funding, and private insurance, either separately or combined. This diversity underscores the challenges and intricacies of reimbursement models across different regions.

The survey findings underscore the critical impact of reimbursement challenges on the availability and equitable access to CAR-T therapies, especially in lower-income regions. It emphasizes the necessity of addressing these issues to improve access to these potentially lifesaving treatments. While commercial CAR-T therapies are costly and face reimbursement hurdles, noncommercial options offer some relief through trial sponsorship. Nevertheless, the variability in reimbursement practices across regions complicates the overall access to CAR-T therapies, highlighting the need for more cohesive strategies to ensure wider availability.

Regulatory oversight and accreditation

The survey responses provided an overview of the perceptions of the regulatory frameworks for CAR-T therapies across various regions, noting significant differences in their effectiveness and focus. While some regions, particularly in Asia, Africa, and South America, concentrate on traditional medical products like blood, tissues, and organs, others are adapting to include modern therapies like CAR-T.

The shift of CAR-T products to being classified as medicinal products in most jurisdictions signifies a regulatory evolution from traditional cell-based therapies, driven by the increasing involvement of pharmaceutical companies in developing and distributing these therapies. This transition emphasizes the need for updated regulatory approaches to address the complexities and ensure the safe integration of CAR-T therapies into global healthcare systems.

Monitoring and accreditation also play crucial roles in maintaining the safety and efficacy of CAR-T therapies. The FDA in the United States mandates a 15-year monitoring period post-therapy, reflecting similar long-term monitoring practices in transfusion medicine. The cellulo-vigilance measures are vital for patient safety and evaluating long-term outcomes of CAR-T therapies. International bodies like the European Society for Blood and Marrow Transplantation can play important roles in starting registries and accreditation systems to standardize practices and improve therapy quality.

Additionally, the survey revealed that geographical disparities exist in the facilities handling CAR-T product release, with variations seen between regions like Australia and North America. These differences highlight the necessity for robust frameworks to ensure equitable access and quality across different regions.

Discussion And Future Directions

The WBMT survey offered interesting insights into the global CAR-T manufacturing landscape and access barriers. Despite promising awareness and interest globally, significant challenges persist in making therapies universally available. Addressing cost barriers requires innovative pricing models, value-based arrangements, and manufacturing efficiencies. Regulatory harmonization could streamline approval processes across jurisdictions. Decentralized manufacturing models show promise for expanding global access, while automation technologies may help standardize production and reduce costs. Global partnerships and knowledge sharing are essential for building capabilities in developing regions, and investment in infrastructure and workforce development is needed to support therapy delivery worldwide. The following summarizes potential barriers, observations of global trends, and recommendations for future directions.

1. Potential barriers for CAR-T therapies
   • Cost is one of the most significant barriers to the implementation of CAR-T therapies. Commercial CAR-T therapies can range from $ 300,000 to $500,000, making them unaffordable for many patients and healthcare systems, especially in lower-income regions.
   • Healthcare infrastructure is a key enabler for the availability of CAR-T therapies in a region. Many centers in lower-income countries may lack the necessary facilities and resources to provide CAR-T therapy, which in turn limits patient access.
   • A lack of uniformity of regulatory frameworks across different countries presents regulatory challenges, which can hinder the approval and availability of CAR-T therapies. In some regions, there may also be insufficient oversight, which may lead to variability in the quality and safety of care.
   • Training and expertise of the healthcare workforce is also critical. The implementation of CAR-T therapies requires specialized training for healthcare professionals. In regions where such training is lacking, the ability to administer these therapies effectively is thus compromised.
2. Observations of global trends
   • Global disparity: The survey results indicate a global disparity in the availability of CAR-T therapies between developed and developing regions. While North America and Europe show relatively high CAR-T availability, other regions, such as Africa and parts of Asia, have significantly lower access, with some centers lacking CAR-T therapies altogether.
   • Future plans for CAR-T: Interestingly, despite the current lack of availability, many centers that do not currently offer CAR-T therapies indicated plans to do so within the next five years. This indicates a potential shift in access, but it remains to be seen if these plans will materialize effectively.
   • Innovative solutions to access: Some centers are exploring alternative methods to centralized manufacturing, such as in-house manufacturing of CAR-T products, to overcome the barriers posed by commercial product availability. This resourcefulness may help bridge the gap in access, but it also raises potential questions about the consistency and quality of the products manufactured.
3. Recommendations for future directions
   • Standardize manufacturing protocols to improve consistency. The development of point-of-care manufacturing solutions would help to address challenges of GMP requirements across centers.
   • Develop harmonized quality standards and regulatory requirements through greater collaboration between regulatory authorities and industry.
   • Create centers of excellence in underserved regions to promote regional expertise and workforce development for cell and gene therapies.
   • Expand applications of CAR-T and cell therapies beyond current indications of oncology. 

In summary, while there are significant barriers to the implementation of CAR-T therapies, including cost, infrastructure, regulatory challenges, and training, there are also signs of potential progress and innovation that could improve access in the future. Success will require coordinated efforts by academic institutions, industry, regulatory bodies, and healthcare systems. With a collaborative global approach, the revolutionary potential of CAR-T and cell therapies can be made available to patients worldwide regardless of geographical region.

Reference:

1. Tan, EH; Aljurf, M; Hussain, F; Chabannon, C; Worel, N; Weisdorf, D; Yakoub-Agha, I; Galeano, S; Sanchez-Guijo, F; Garderet, L; Atsuta, Y; Ruggeri, A; Hamad, N; Hashmi, S; Frutos, C; Kodera, Y; Seber, A; Bonfim, C; Niederwieser, D; Rondelli, D; Greinix, H; Koh, MB Perspectives on the use and availability of chimeric antigen receptor T cells (CAR-T) and cell therapies: A worldwide cross-sectional survey by the worldwide network for blood and marrow transplantation (WBMT). Curr Res Transl Med. 2025; 73(2):103515 Doi: 10.1016/j.retram.2025.103515

About The Author:

Eddie H.P. Tan is an assistant professor at the Centre of Regulatory Excellence at Duke-NUS Medical School  National University of Singapore (NUS). He currently co-leads a collaborative project with the Ministry of Health in Singapore to study regulatory innovation of emerging healthcare technologies. He has more than 10 years’ experience in the development of cell and gene therapies, most recently as scientific officer of the National Cell and Gene Therapy Facility in Singapore. He is experienced in process and analytical development, validation and qualification, and quality management systems for cell and gene therapy clinical manufacturing.