Cell and Gene Therapy Answers: What to know about companion diagnostics development
A companion diagnostic (CDx) is an in vitro diagnostic providing essential information for the safe and effective use of a corresponding therapeutic product. By identifying patients most likely to benefit from or who are at risk of adverse events from a therapy, CDx can help guide decisions for targeted treatment strategies—which is why many regulatory bodies now recommend incorporating CDx within cell and gene therapy (CGT) programs. However, for many developers, questions remain about when CDx are truly needed, how to choose the right CDx partner and the kind of testing required for CDx assays. To gain clarity on CDx strategy and best practices, we spoke with Devin Craven, associate director of regulatory affairs for Labcorp, and Laura Huning, a scientist for Labcorp’s diagnostic development services.
How do you know if you need a CDx for your gene therapy program?
A CDx could be required for your gene therapy if the assay is used to identify patients who will most likely benefit from the treatment or who may be at an increased risk of adverse events. Alternatively, a CDx could be used to monitor a patient’s response to a treatment for the purpose of adjusting the adjusting dose, in order to improve safety or efficacy. The prevalence and predictive value of a biomarker within a population may also influence whether testing with a CDx is necessary.
To determine whether a CDx may be needed specifically for your gene therapy, early engagement with regulators is key. This communication can help determine the potential need for a CDx and can help inform the regulatory strategy and assay design. Here at Labcorp, we routinely help our gene therapy clients perform study risk determinations to evaluate the need for an IDE and we lead pre-submission meetings with the FDA early in the development process. Based on our pre-sub experience, we can provide our partners with firsthand knowledge on choosing and developing the most appropriate assays and determining what analytical validation studies may be required to ultimately support the use of the assay in a clinical trial. In the end, this early engagement, combined with Labcorp’s knowledge and experience, results in both time- and cost-savings for our partners.
In fact, it is this experience that enabled us to bring the first cell-based neutralizing antibody assay CDx to market to help determine patient eligibility for treatment with BEQVEZ™ (fidanacogene elaparvovec-dzkt), Pfizer's recently FDA-approved hemophilia B gene therapy.
What are some considerations for choosing a CDx partner?
Because of the novelty and the complexity of gene therapies, in addition to this ever-changing regulatory landscape, it is important to find the right CDx partner who has both the technical and regulatory expertise needed within the gene therapy space. You also want a reliable and responsive lab with an understanding of your development timelines and who can integrate their CDx timelines to achieve contemporaneous approvals.
- CDx team with a proven track record in IVD development and design control experience for both total antibody and neutralizing antibody assays, in addition to a range of other biomarkers across a variety of technologies and platforms
- Development scientists who are experienced in engaging with regulatory authorities and understand the design and performance of CLSI analytical validations with careful consideration to the level of testing required and study design and assay parameters, such as analytical and clinical cutoffs
- Regulatory team combining both industry and ex-regulator experience that can provide regulatory support across the CDx life cycle from early feasibility through commercialization
We work closely with both the biopharma customer and its internal research and development, quality, and manufacturing teams to develop and execute the appropriate regulatory strategy. We also handle every facet of CDx regulatory approvals, including authoring FDA, EU and rest-of-world submissions. These include but are not limited to:
- Q-subs
- Study risk determinations
- IDEs
- PMAs
- Technical files
- Performance study applications under IVDR
Lastly, our CDx facilities are 21 CFR Part-820 compliant and ISO 13485 certified; we also have manufacturing capabilities to produce kitted solutions for deployment across our global lab network with Labcorp.
When do you need to start planning for a CDx assay and what testing will be required?
In general, for U.S. studies, we recommend that a study risk determination be conducted early on in the process to determine whether an IDE will be needed and to help guide the level of analytical validation required. For cell and gene therapies specifically, the FDA has communicated that the use of these assays within a clinical trial is often considered “high risk” and they therefore expect rigorous validations regardless of trial phase at almost a “PMA” level. Engaging with regulators early in the process may help to mitigate some of the regulatory risk. For example, pre-submission meetings with the FDA can help sponsors to better align on the required analytical validation strategy.
The timelines for CDx development are highly dependent on the assay and its intended use, but on average, it takes about 15-18 months to develop and validate a test before it can be used to support an IDE and clinical trials, and more than 5 years to commercialize a new CDx assay. In the tAb space, our development team has done work upfront and is able to reduce these timelines in certain instances. The timeline to commercialization depends on the stage of the clinical trial and the length of the drug study. Likewise, the CDx timeline follows the drug review for contemporaneous approval. At this time, a CDx for a gene therapy is considered a Class III device in the U.S. and requires a PMA or HDE. These review processes can be lengthy and may take up to a year, further suggesting the need for early planning and a coordinated co-development effort between the drug and assay manufacturers.
Advance your CDx journey
Gene and cell therapies provide new possibilities for diseases previously thought to be untreatable, making the role of diagnostics more important than ever. With our mission to improve health and improve lives, we are committed to advancing CDx development that delivers individualized therapies to patients. Our access to diverse biomarker expertise—from development to validation—and track record supporting several FDA-cleared or -approved CDx devices means we can help drive your CDx development forward at any stage.
Ready to start a conversation? Contact our team today or read more from our CGTAnswers blog series.