By Megan Liles, Executive Director, Operational Strategy and Feasibility, Precision for Medicine
With several gene and cell therapies currently in development and even more rapidly moving toward the development stage, a big bottleneck in this evolving field is identifying sites with the capability and capacity to conduct these resource-intensive studies. Research in this sector is concentrated, with over 1,000 gene and cell therapy developers active globally, according to the Alliance for Regenerative Medicine. As of the end of Q3 2020, there were nearly 1,100 clinical trials ongoing worldwide, 97 of which are in Phase 3.1
Established sites, such as City of Hope in the US, Peter MacCallum in Australia, and The Christie in the U.K. are often the go-to centers for gene and cell therapy studies but may have long wait lists. Gene and cell therapy developers need to create clinical interest to find champions at investigative sites and, differentiate their products and clinical trials to keep development moving forward.
In this article, we explore strategies for building clinical enthusiasm and selecting the right sites for gene and cell therapy trials.
Building Clinical Enthusiasm: From Bedside to Bench and Back
Having a well-designed, patient-centric study protocol is essential for site and participant recruitment. When looking to develop a therapeutic in this space, developers should first engage with not only clinicians who are treating patients with the indication of interest, but also patients, medical and scientific experts. Understanding the perspectives and pain points of each of these stakeholders can help inform therapeutic and protocol development as well as create clinical enthusiasm. This level of engagement is also an opportunity for patient and provider education, as knowledge and understanding of these advanced therapies is highly variable. Taking this feedback all the way back to the bench helps ensure that investigative therapies target appropriate mechanisms of disease and the right study endpoints are evaluated throughout every stage of the clinical development plan.
Manufacturers should initiate the process of building clinical enthusiasm at the earliest stages of development as it takes time to identify champions and cultivate investigator and site relationships. Investing time in understanding site level clinical workflows and potential gaps contributes to the development of study protocols that require less friction to implement. Incorporating patient and caregiver feedback is also vital for generating awareness and enthusiasm among those whom the gene or cell therapy is designed to benefit. Developing a deep understanding of patient and caregiver concerns related to treatment is valuable, particularly with gene therapies that are one-off treatments where efficacy outcomes are often binary.
Those who are cognizant of minimizing clinical trial-related participant and site burden are likely to be more successful in recruiting and retaining patients and maintaining strong relationships with investigators and site staff. Putting in place processes for ongoing site training and certification will reduce barriers to participation. Building and maintaining this rapport is essential for gene and cell therapy studies, which often require a long-term follow up period that may be as long as 15 years.
Due to the complex requirements of gene and cell therapy trials, site identification, qualification, and selection are critical components of study success. A prerequisite for any site is the experience necessary to coordinate the specialized activities involved in administering these advanced therapies.
Criteria for assessing the quality and readiness of sites include:
- Relationships with referring providers for access to patients with the indication of interest and delivery of post-treatment care
- Presence of a champion to ensure appropriate prioritization of the clinical trial
- Resources necessary for the delivery of gene and cell therapies, including in-house or nearby apheresis and cryopreservation capabilities and appropriate logistics and chain of custody processes
- Institutional accreditation from the Foundation for the Accreditation of Cellular Therapy (FACT) or the Joint Accreditation Committee ISCT-Europe & EBMT (JACIE), which have established international standards for the collection, processing, and clinical use of cellular therapy products
- Reputation and past performance in gene and cell therapy studies, including the ability to communicate and coordinate among interdisciplinary departments
- Existence and impact of competing trials
- Availability of adequate hospital facilities for post-infusion monitoring and follow up, as well as institutional protocols for managing toxicities
To facilitate the site certification process, it may be useful to examine how protocol requirements align with existing institutional policies at each site. It may also be beneficial to take a long-term view to site selection by considering how clinical trial sites can ultimately be converted into commercial treatment centers post approval.
Partnering with a contract research organization (CRO) that has gene and cell therapy experience and an extensive network of investigative sites can facilitate the site selection process. Not surprisingly, prestigious academic medical centers and tier-one hospitals are highly sought after as partners for gene and cell therapy clinical trials. Garnering interest from these sites, however, can be challenging especially as the field grows increasingly crowded. Biotech drug developers seeking partners will be competing against not only other pharmaceutical and biotech companies, but also internal projects that investigators within these institutions are seeking to advance.
Widening the search to include other leading academic medical centers and qualified community-based hospital systems is an effective strategy for increasing study awareness and building clinical enthusiasm. A growing number of institutions have achieved the necessary accreditation for administering gene and cell therapies, opening up the field of eligible sites. Manufacturers may be surprised at the number of off-the-radar sites that have the expertise and capabilities to conduct gene and cell therapy trials. In a recent survey conducted by Precision for Medicine of more than 45 oncology research sites, over 60 percent reported experience with cell therapy studies, 53 percent have access to an apheresis center and cell lab that is a part of their main institution and approximately 50 percent indicated they had FACT or JACIE accreditation. The added benefit of focusing on lesser-known sites is broadening access to local patients who might otherwise not consider clinical trial participation due to the need for long distance travel.
A recent study estimated that, by 2030, 350,000 patients will have been treated with gene and cell therapy products. Delivering these advanced therapies is a highly choreographed and expensive endeavor. Selecting sites, investigators, and patients who are excited about participating in a trial is a cornerstone of study success. By building clinical enthusiasm and looking beyond the go-to sites, developers can streamline the clinical trial process and accelerate access to these advanced therapies.
 Aiyegbusi OL, et al. Patient and public perspectives on cell and gene therapies: a systemic review. Nat Commun. 2020;11(1):6265.
 Precision for Medicine. Oncology Site Network Ideal Site Assessment Survey, 2020.
 Quinn C, et al. Estimating the clinical pipeline of cell and gene therapies and their potential economic impact on the US healthcare system. Value Health. 2019;22(6):621-626.