On Wednesday, March 8, Friends of Cancer Research (Friends) hosted a virtual meeting titled “The Next Generation of Cellular Therapies: Opportunities to Accelerate Development.” This meeting sets the stage for a meeting on May 22 in Washington DC by providing context around the current state of the science and progress in cell therapy development. These advances have made it possible to explore innovative development strategies that leverage current learnings to optimize development of the next generation of cell therapy products. The meeting on May 22 will focus on these solutions. Click here to register to attend virtually or in person.
Jeff Allen, President and CEO of Friends, started the virtual meeting by introducing the keynote speaker, Peter Marks, Director of the Center for Biologics Evaluation and Research (CBER) at the U.S. Food and Drug Administration (FDA). Dr. Marks emphasized how focus on cell therapy product development is continuing to increase, noting that last year the FDA received close to 100 applications for chimeric antigen receptor (CAR) T-cell therapies. He also discussed the future of autologous and allogeneic cell therapies and their potential to treat solid tumors as well as in earlier lines of treatment for hematologic malignancies. Dr. Marks also discussed other opportunities to move the field forward, including addressing challenges associated with commercial manufacturing of cell therapies and the potential of basket trials to enable efficient development.
“I think there is a lot of excitement here in part because once you can make multiple genome edits into these cells you can potentially have more complex constructs.” – Peter Marks, U.S. FDA
Following the keynote, Dr. Julie Jadlowsky, Director of the Center for Cellular Immunotherapies at the University of Pennsylvania, and Dr. Jonathan Jazayeri, Executive Director of Global Regulatory Affairs at Kite, A Gilead Company, presented on the academic and industry experiences, respectively, of leveraging existing data to support the development and regulatory reviews for novel cell therapies. Dr. Jadlowsky’s presentation described how pre-existing data was used to justify reducing/removing the need for continual testing on the same product or a similar version may not provide additional value, such as additional replication-competent retrovirus/lentivirus (RCR/L) testing. She also discussed how emerging safety and persistence data could be leveraged to reduce the duration of long-term follow-up while maintaining rigorous evaluation of the long-term safety of lentivirus-modified cell therapies. Ultimately, this can help reduce burden on patients and enhance the relevancy of data collected. Dr. Jazayeri presented a case study on using data extrapolation to streamline regulatory submissions and approval for two CAR-T cell products. He detailed how dosing, stability, and safety data from YESCARTA (axicabtagene ciloleucel), a cluster of differentiation 19 (CD19) directed CAR T-cell therapy, were leveraged to accelerate the development of a next-generation CD19-directed CAR T-cell therapy, TECARTUS (brexucabtagene autoleucel).
“YESCARTA is an example of where a next generation cell therapy product made it to the clinic and was able to accelerate or skip some of these traditional first time in human steps and ultimately resulted in a successful program which was able to deliver a treatment to patients sooner.” – Jonathan Jazayeri, Kite, A Gilead Company
The event then transitioned to a panel moderated by Michael Kalos from Next Pillar Consulting with panelists Drs. Marc Better from Pharmefex, Ingrid Markovic from the FDA, Julie Jadlowsky, and Jonathan Jazayeri.
To begin the discussion, Dr. Markovic summarized the FDA’s perspective on how Friends’ work, regulatory guidance documents, and programs help to support advancements in the development of cell therapies. Drs. Jazayeri and Jadlowsky reiterated the importance of using past data and experience to streamline preclinical and phase one trials. Dr. Markovic then spoke about the importance of identifying the similarities and differences between products to effectively extrapolate data from one product to another while ensuring changes did not lead to reduced safety or efficacy. She also described the importance of understanding the different types of changes that would make a product a new product versus a new product version. Piggybacking off that idea, Dr. Jazayeri suggested the FDA develop a pathway to provide regulatory flexibility in instances where there has only been a change to a manufacturing process, as opposed to a change that would constitute an entirely new product, to avoid redundant work that could delay patient access to improved product versions. When asked about approaches to understanding differences between primary and secondary products, Dr. Better noted the importance of having analytical tools for characterizing the biological properties of products to inform the development of new iterations over time. Drs. Markovic and Better both discussed how product sponsors can leverage data that comes from a wide range of sources. Drs. Jazayeri and Jadlowsky then discussed regulatory considerations for preparing an investigational new drug (IND) application submission and how pre-existing data can be used to provide context. The panel concluded with the speakers giving their thoughts on how appropriate regulatory flexibilities and tools can be incorporated into a regulatory framework to enable continued improvements to cell therapy products.
“There is a whole myriad of things that could potentially cause unplanned interruptions in operations. Anticipating this ahead of time could help with coming up with a mitigation plan and could go a long way to help inform and streamline development.” – Ingrid Markovic, FDA