Regulatory Focus™ > News Articles > 2021 > 5 > Actionable insights for successful development of cell and gene therapies

Actionable insights for successful development of cell and gene therapies

Posted 01 May 2021 | By Kevin Hennigan 

Actionable insights for successful development of cell and gene therapies

Cell and gene therapy (C&GT) products are beginning to deliver on their long-hoped-for promise. CAR-T technology has proven to be a powerful new weapon in cancer treatment, and FDA approval of Luxturna in 2017 demonstrated the potential of gene therapies to be used outside of oncology. As both cause and consequence of this success, development and clinical trial activity in these product classes is accelerating. There are over 1,200 active clinical trials in regenerative medicine and advanced cell/gene therapies in 2021, up from 700 in mid-2019. As the field expands, what lessons have we learned to improve the efficiency of development for these products? What pitfalls can be avoided? As you initiate cell and gene therapy studies, here are some of our key takeaways that may help.

Place patient safety first

The history of the C&GT field is marred by clinical studies that went disastrously wrong. The field has learned painful lessons from these missteps. Thorough pre-clinical safety evaluations, cautious clinical trial design, careful evaluation and classification of adverse events are fundamental considerations to ensure patient safety, satisfy regulatory expectations, and advance development. Risk is an inherent part of new drug development, so we encourage sponsors to work closely with their chosen contract research organization (CRO) to incorporate appropriate safety measures, including dose escalation protocols, study stopping rules, and safety monitoring, into their trial design to ensure the particular risks of C&GT products are properly managed and balanced with the potential benefits.

Establish good communications with regulatory authorities

Sponsors are sometimes reluctant to open a dialog with the US FDA, EU EMA and other regulatory authorities, perhaps fearing the imposition of new requirements, but in our experience, avoiding regulatory conversations is rarely a productive approach. These regulatory authorities are the gatekeepers, so ultimately their expectations will have to be met, and the only question is whether you will learn about those expectations early or late in the development process. More importantly, the regulators have an advantage in being exposed to non-public data from a diverse array of programs. Regulators will often use insights from that knowledge to guide programs away from pitfalls that could delay or even doom development. We encourage our clients to utilize the FDA INTERACT program, EMA Scientific Advice meetings, and other opportunities to engage in discussion directly with the regulators frequently during the development program.

The importance of an experienced, integrated team

Clear communication is a critical success factor in any endeavor but can be particularly emphasized in C&GT development. Modest changes in the manufacturing process can have a significant effect on everything from regulatory submissions to clinical trial design to operational logistics. Consequently, it is important to have a cross-disciplinary team of experts who work well together to navigate the ups and downs of development. That said, outsourcing remains an essential element of biotech development, as it is extremely difficult, if not impossible, for startup companies to hire subject matter experts who can cover all the disciplines. Engaging the right full-service CRO as a partner, if they have the experience in the C&GT space to cover your gaps, can be a great way to bridge from early development through pivotal trials.

Be prepared to re-think your plan

Early and long-term planning are central to pharmaceutical development. Sometimes overlooked, however, is the importance of remaining flexible and periodically re-evaluating the Gantt chart. The C&GT landscape changes quickly: competitor news, roadblocks in assay development, updates to regional regulations and guidance, or serendipitous clinical findings can and should spur a reassessment of the program’s strategy and objectives. Engaging a third party to conduct a gap assessment or review the road map can help limit the bias that sunk costs (intellectual and financial) can create.

Expect complexity

Development of C&GT products is complex. Everyone who pursues this product class understands that basic fact. Nevertheless, that complexity can manifest in ways that are both surprising and frustrating. As an example, in one program, required long-term follow-up data from three clinical trials were originally planned to be collected into a single database, but mid-study design updates resulted in a need to split the database; first into 2, and ultimately into 3, one dedicated to each trial. Autologous cell therapy products can have unpredictably variable manufacturing timelines and relatively short stability intervals, introducing complexity into the scheduling process for both the CRO and investigators. Regulatory complexity is a factor as well. Even within the EU, C&GT products are regulated differently from nation to nation, creating challenges for manufacturing, distribution, and study recruitment.

Explore central site models and other innovative trial designs

Recruitment for C&GT trials, often targeting rare diseases or restricted population subsets, can be a significant challenge. In addition, some C&GT products require specialized facilities for patient screening, cell harvest, or treatment administration, placing  significant stress on traditional distributed site network models. Centralized site clinical trial models, where critical processes such as treatment are done at a central site with remote/local follow up, can help address both issues, reduce costs, and reduce the burden of study participation for the patient. Exploring this and other innovative trial design options can significantly improve the efficiency of clinical development.
Cell and gene therapy products are poised to deliver major advancements in human health. Strategic incorporation of the lessons learned from the pioneers in the field will continue to accelerate their development.

Get the case study now

For an example of how engagement of an integrated CRO team helped to successfully usher a program through the entire clinical development life cycle, from Phase 1 through to BLA submission, read our case study now or contact Veristat for a thoughtful assessment of your C&GT program.

Kevin Hennegan is senior regulatory strategist at Veristat. 
 

 

© 2021 Regulatory Affairs Professionals Society.
This article is sponsored and does not reflect the views or opinions of RAPS. The sponsor is solely responsible for the content presented.

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