Cell and gene therapy answers: The importance of designing trials and strategies with the end goals in mind

The cell and gene therapy landscape is experiencing a season of exponential growth within drug development. With more assets entering preclinical development every day, Labcorp underscores the importance of designing trials and strategies with the end goals in mind from the very beginning.

1. What are the key elements necessary for designing a cell therapy development plan?

What we really emphasize is early and comprehensive planning for every aspect of your program. This means planning with the end in mind, understanding the five key elements for your program from the beginning: preclinical, CMC, regulatory, clinical and commercial.

The strategy and timing of execution of each of these individual elements affects the strategy and execution of each of the others. For example, you must understand your clinical program to effectively plan your nonclinical activities, such as model selection for pharmacology and toxicology studies. Another example is ensuring that your CMC program will have the appropriate scale to support your clinical and commercial plans. And of course, regulatory strategy and understanding the evolving regulatory environment is the unifying factor at every step of development.

2. So, where should clinical trial investigators begin?

At the start of every cell and gene therapy program, we recommend drafting a target product profile (TPP). The TPP provides the perfect planning tool to identify the desired attributes of your product and what studies, both nonclinical and clinical, are needed to support those attributes. It also helps to guide program requirements and focus interactions with the FDA.

Since we have seen hundreds of programs, we understand the requirements for the different regulatory bodies. Our cell and gene therapy consultants can help you develop your TPP and plan your programs accordingly, which allows for a more focused development pathway that will be more time and cost effective.

3. What surprises clients most when they first contact to conduct in vivo studies?

Clients tend to be most surprised that there can be significant lead times before an in vivo study and the supporting analytical work can begin. Today, there is high demand for cell and gene therapy programs and CRO resources, and even top CROs with excellent capabilities and expansive teams are bound by lead times.

Frequently, clients will establish budgets and timelines for key program milestones with investors and then approach CROs about executing studies, only to find that resources are unavailable to meet those budgets and timelines. Sometimes, they will resort to working with inexperienced partners who promise a quicker start but may result in regulatory rejections, further delaying the program or requiring repeat work, thereby increasing costs and affecting timelines. So, we recommend working closely with an experienced CRO like Labcorp* on program development and regulatory strategies and understanding those timelines and costs before promising milestones and budget requirements to investors.

4. What are key considerations when planning in vivo safety/toxicology studies?

The primary consideration for planning in vivo safety and toxicology studies is very early planning. There has been growing demand for resources in the cell and gene therapy landscape that has led to long queues for the conduct of pivotal safety and toxicology studies.

Understanding your product is also key; how it will be delivered, whether prescreening for preexisting antibodies is required and whether immune suppression will be required are examples of factors that can impact the timing and conduct of your study. Moreover, cell and gene therapy products are complex, and the anticipated biological effect can take much longer to completely evaluate compared to traditional drugs.

Another important consideration is the host of analytical testing that accompanies these studies: dose analysis, molecular bioanalysis (such as PCR-based methods), transgene bioanalysis and immunogenicity, immunology and immunotoxicity. These tests typically require method development, optimization and validation and, of course, time and resourcing.

When starting from scratch, these activities can take up to six months, and this doesn’t take into account the previously mentioned lead time or the time needed to get the appropriate materials and reagents in place ahead of the work. Clients need to plan these activities well ahead of starting their pivotal studies so that the assays will be ready to execute as soon as samples are available from the study. Finally, there is the time required to perform sample analysis for the study and the time needed for reporting.

So, considering analytical development and validation, longer times needed for in-life evaluations, and end-of-study analysis and reporting, pivotal safety and toxicology studies for some of these complex cell and gene therapy products can take at least a year to execute.

5. What are additional factors that can impact program development timelines?

There are several other factors that can impact development timelines.

The desire to rapidly hit milestones can sometimes prompt teams to design and perform study work that isn’t necessarily aligned with what regulations actually require. This can be okay for discovery work but is not ideal for the preclinical IND-enabling work. Therefore, crafting the regulatory strategy first and then taking informed actions on corresponding studies and analyses ends up being a more cost- and time-effective approach. We know that guidelines are evolving and can be challenging to navigate, and that’s why you must have that plan in place early and work with an industry leader like Labcorp to avoid unexpected delays, such as chasing “nice-to-haves” versus informed analyses.

Another factor is manufacturing. The manufacturing timeline can become a bottleneck in starting and executing cell and gene therapy programs. Contract development and manufacturing organizations can also have lengthy lead times. Timing of CMC activities—process development, analytical development, validation, manufacturing and product release—must align with preclinical and clinical timing. Any delays in the release of your product can cause delays in study execution. So, we recommend that while the product is being manufactured, talk with your CRO partners to help coordinate timelines and make necessary arrangements for suitable start dates for your study.

Essentially, start with the end in mind. When companies plan and start preclinical work with the end goal in mind, it’s easier to craft a robust clinical strategy, set clinical endpoints and manufacture scale-up strategy, easing the transition from preclinical to clinical studies. Working with a CRO like Labcorp* that offers end-to-end support with classically trained and experienced teams across the development continuum can eliminate the white spaces, as we can help you seamlessly advance your program to the clinical phase, providing CMC analytical and regulatory support, clinical protocols for IND filing, clinical trial execution* and, finally, commercial support*.

Jump-start your cell and gene therapy development by visiting biopharma.labcorp.com/cgt