With the recent approval of two new gene therapies for sickle cell disease,¹ one of which involves an ex vivo genome editing technology, cell and gene therapies (CAGTs) remain in the spotlight. Further successful clinical trials will be needed for the potential of these transformative therapies to be realized in other conditions that were previously untreatable. Progress is encouraging, with launches of up to 21 cell therapies and 31 gene therapy expected in 2024, according to a September 2022 McKinsey article.²

Salient defining operational characteristics of CAGT trials include: complex protocols, frequently dealing with rare populations of patients; the need for logistics management for expensive and often irreplaceable assets; the requirement for specialized centers; and accelerated timelines.³ Multiple approaches and solutions have been designed and deployed to address all these challenges. Working with specialized entities such as patient advocacy groups and specialty logistics companies can help CROs find patients and address complex logistics. These particular topics were discussed in a panel entitled, “Streamlining Clinical Trial Success: The Power of Partnerships,” at the 2023 Cell & Gene Meeting on the Mesa (Carlsbad, CA; October 10-12, 2023).⁴ Recent IQVIA White Papers also examine CAGT logistics management challenges and solutions.⁵

Four key elements are essential to the success of CAGT development programs, and ultimately, to patient access to these important therapies:

Patient recruitment and retention: The complexity of making and administering cell and gene therapies, together with the risk they pose and public caution, can cause delays in recruitment. High screen failure rates may also result from genetic screening or use of non-routine biomarkers for rare and genetic diseases. To address delays, investment may be needed in areas such as setting up registries, developing pre-screening protocols and additional data on biomarkers, and collaboration with patient advocacy groups. Having sustainable ways to identify patients is a vital step towards commercialization. Patient-centric protocols can increase patients’ willingness to participate in the long-term follow-up that is essential to support regulatory decisions, as well as pricing and market access discussions. 

Logistics: Challenges during the CAGT asset journey include tight pick-up windows, length of time from manufacturing to administration of the therapy in the case of autologous models, cell viability in transit with temperature excursions compromising the quality of the IP, and importation/exportation requirements that may delay timelines. Added to this, supply chains involve multiple specialty vendors. Logistics must accommodate therapy-specific conditions, including requirements for scheduling and specific temperatures. Account must also be taken of the type of platform used (allogeneic or autologous) and the fact that highly targeted delivery and administration can result in more handoffs of the therapy, requiring multidisciplinary teams at sites. Sponsors have to examine potential tradeoffs between multiple manufacturing locations or international shipping for global studies; these choices also have implications for commercialization. 

Country and site selection: To be suitable for CAGT clinical trials, countries must have in place a regulatory framework for genetically-modified therapies. Beyond this, sites must have specific facilities and experience in order to run high-quality studies. The choice of excellent sites and Principal Investigators supports strong regulatory submissions and relative ease of approval. While ideally, sites should be close to target patients, the limited number of qualified study sites is likely to increase overall burden and willingness to participate for participants. Data-driven site identification and site networks can be helpful in identifying additional sites. The countries and sites used for clinical trials will inevitably be the starting point for commercialization of the therapy; early investment in sites near target patients can support market success.

Democratization of clinical trials and access to therapies: Access to CAGT is challenging in the developed world, yet there is also great need for these innovative therapies in regions such as Latin America, Asia-Pacific and Africa. For several of the diseases targeted by CAGT, most of the patients who could benefit live in low- and middle-income countries,⁸ with little or no access to these therapies or even to standard of care. Democratization of clinical trials – which involves increasing access and inclusion, and can improve healthcare – is a high priority for IQVIA. Virtual clinical trials and the technologies that make them possible can support democratization by boosting engagement with a wider range of clinical research centers. 

Another organization that works to democratize access to trials is the Myeloma Foundation. Speaking on the Cell & Gene Meeting on the Mesa panel, Mimi Choone-Quinones, Ph.D., MBA, described efforts to take CAGTs to African patients. By increasing patient access to new therapies that can improve outcomes and reduce productivity loss, the foundation aims to reduce the ‘financial toxicity’ of multiple myeloma. This can potentially be achieved by improving patients’ prognosis while reducing direct health care payments.11 In an initiative termed ‘cross-border’ trials, industry grants are given to bring spinal muscular atrophy patients from low- or middle-income countries that lack study sites. These funds support the patient and their family for the six months they must spend close to the study site, which is typically in a metropolitan area of a developed country. They also facilitate participation in the five or more years required for the study and follow-up. The Myeloma Foundation has also worked with African Union lawmakers to advance legislation that provides a tax exemption for any CAGTs launched in that continent.

Strategies for these four aspects of development – patient recruitment and retention, logistics, country and site selection, and democratization of clinical research – can support successful CAGT development. Partnerships with specialist vendors can bring tailored expertise to each of these areas, helping achieve clinical and ultimately commercial success, along with much-needed patient access to these promising therapies.

References

¹ U.S. Food and Drug Administration [Internet]. FDA; 2023Dec8 [cited 2024Feb15]. News release, FDA Approves First Gene Therapies to Treat Patients with Sickle Cell Disease. December 8, 2023. Available from: https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease

²  Alfano S, Gorham A, Loche A, Salazar P. Eight imperatives for launching cell and gene therapies. McKinsey website [Internet]. 2022Sep22 [cited 2024Feb15]. Available from: https://www.mckinsey.com/industries/life-sciences/our-insights/eight-imperatives-for-launching-cell-and-gene-therapies (September 20, 2022)

³ Upadhyay N, Correa D. Cell and Gene Therapy Logistics: How partnerships can challenges in the cell and gene therapy asset journey [Internet]. IQVIA; 2023Oct6 [cited 2024Feb15]. Available from: https://www.iqvia.com/library/white-papers/cell-and-gene-therapy-logistics

⁴ Alliance for Regenerative Medicine. Streamlining Clinical Trial Success: The power of partnerships [Internet]. 2023 [cited 2024Feb15]. Available from: https://www.youtube.com/watch?v=ABE2pr_4m3s

⁵ Sacarakis N. Cell and Gene Therapy Logistics Management: A holistic approach [Internet]. IQVIA; 2023Jun7 [cited 2024Feb15]. Available from: https://www.iqvia.com/library/white-papers/cell-and-gene-therapy--logistics-management-a-holistic-approach

⁶ Alliance for Regenerative Medicine. Democratization of Transformative Cell & Gene Therapies Workshop [Internet]. 2022 [cited 2024Feb15]. Available from: https://www.youtube.com/watch?v=4y_jmZ0YZjM