Cell and gene therapies, which fall under the general classification of advanced therapies, are more complex and specialized than traditional drugs. They can involve correcting or replacing genetic information and engineering the correct functionality of cells or genes for many conditions, including cancer and rare diseases with a genetic basis. As these therapies gain traction, sponsors seek drug development partners that can help them navigate the challenges associated with these therapies across the drug development continuum.

LabCorp, through its drug development business, Covance, has introduced a suite of cell and gene therapy development services that aim to reduce time and risk for sponsors at each phase. Covance provides specialized capabilities to support preclinical, clinical and post-approval phases of development. By offering a coordinated approach to scientific and program consultation, biomarker and companion diagnostic development, study management, regulatory and commercialization support capabilities, Covance aims to help address complexity, reduce cost and risk, and accelerate timelines.

Dr. Steven Anderson, Chief Scientific Officer at Covance discusses outsourced services in the cell & gene therapy space and some of the biggest challenges developing these complex therapies and how they can be overcome. –KB

Contract Pharma: What services do sponsors seek in the development of cell & gene therapies? How do they differ from traditional drug development/CRO services?

Dr. Steven Anderson: At the most basic level, sponsors for cell and gene therapies need the same answers that are critical in bringing traditional drugs or devices to market. They want to understand how a therapeutic candidate works and whether it will be safe and effective to move into clinical trials. Sponsors want the ability to identify and screen patients and conduct well-designed trials. And they want to get the treatment to market as quickly and cost-effectively as possible.

The methods for accomplishing these tasks for cell and gene therapies may, however, be very different from those used in more traditional drug development. For example, patient populations are often very small and targeted for either a specific cancer subtype, or a genetically defined and often rare disease. Trial designs for gene therapies for rare diseases also often use surrogate endpoints of response as a measure of efficacy.

Also, there are often a broad spectrum of biomarkers assays that may be applied to assist with PK/PD and dosing assessments of the cell or gene based therapy, and toxicity studies that look at the response to the therapy or integration sites for the gene based therapies. Efficacy measures for adoptive T-cell therapies include biomarker assays that measure the persistence of the engineered cell therapy over time, as well as levels of the targeted cell population, and the detection of residual disease.  These assessments involve a wide range of technologies including genomics and cell-based methods

With this level of complexity, it’s important to look at the entirety of the development pathway. A CRO with deep experience in the rapidly changing landscape of advanced therapies can provide a more holistic framework beyond traditional services, offering specialized support for study design in both the preclinical and clinical phases, regulatory review, manufacturing and logistics, companion diagnostic development and market access.
 
CP: What are some of the biggest challenges developing these complex therapies and how can they be overcome?

SA: Because these therapies are most often targeting life-threatening conditions, they often are considered for breakthrough therapy consideration with accelerated timelines and expedited regulatory approval pathways. That means sponsors need to be able to transition quickly from nonclinical into clinical development, removing as much whitespace as possible from a highly complex process. That requires having a strong study design and development pathway.

At the clinical trial stage, there are a number of challenges pointed out above that are often linked to the fact that they address smaller, more widely distributed populations that can be difficult to identify and reach. It becomes necessary to try new approaches, such as the partnership between LabCorp Diagnostics and Covance Drug Development to use more conveniently located Patient Service Centers for some patient identification and testing, or utilizing virtual trials through mobile devices.

In addition, because of the novel nature of the therapies and the smaller target population there are commitments for long term as compared to traditional drug therapies.

CP: In what areas do CROs need to invest in to provide these highly advanced services?

SA: The technology and expertise in cell and gene therapy is constantly evolving, and because these specific types of therapies are individualized there may be a need for custom biomarker assays and applications.  This includes incorporating new technologies in areas such as cell-based and genomic methods. CROs need to stay at the forefront of science to provide sponsors with the resources necessary to help these therapies continue to advance.

CP: What do you anticipate for outsourced services in the cell & gene therapy space going forward?

SA: With the projections for an increasing number of trials and applications in the cell and gene therapy space we anticipate a concomitant increase in outsourcing of services.  Covance with its long history in this space, along with deep scientific expertise and enterprise solutions will be a strong partner for biotech and pharma clients actively pursuing strategies in cell and gene therapy.