Companion diagnostics (CDx) are IVDs developed for the purpose of identifying a characteristic that increases the likelihood of patient responsiveness to a specific treatment. Companion diagnostics will take on increasing importance with the growth of precision medicine. Some aspects of the future of dedicated companion diagnostics are unclear as understanding of complex disease mechanisms increases, Next Generation Sequencing becomes more commonplace and the “one biomarker, one drug, one companion diagnostic” model confronts economic and scientific challenges. Nevertheless, for the foreseeable future, this model seems likely to dominate precision medicine, selection of targeted treatments for patients and inclusion of appropriate subjects in clinical trials. Therefore, coordinating drug and CDx development is a priority for both biopharma and IVD companies.
In developing companion diagnostics for investigational drugs, pharmaceutical companies must keep several key points in mind:
- The earlier in the process of drug development the companion diagnostic can be developed, the better. There are many steps involved in both drug and CDx development that are difficult to accelerate as described in item 2. Therefore, an early start is essential.
- Whenever possible, representatives from the drug development organization and CDx development organization should have at least a basic understanding of both the pharmaceutical and CDx/IVD development processes. This is easier said than done. There are numerous steps in the development process for a CDx, some of which may not be understood by drug developers and some by IVD developers. Examples of steps in IVD development that may not be familiar to drug developers include determination of appropriate specimen type, volume for testing, test methodology, interfering substances, and limits of blank, detection, and quantitation. It is also essential to investigate interfering substances and determine appropriate process modifications to ensure that the CDx functions as intended. Similarly, many IVD developers have had limited exposure to the full range of such issues in drug development as manufacturing a sufficient volume of investigational product, completing preclinical testing, selecting route of administration, determining safe and effective dose, and so on. Any time a team shares at least a basic understanding of all of the steps involved in completing a project successfully, there is a greater chance of anticipating, recognizing and addressing problems while they remain manageable. Additionally, shared understanding of the drug and CDx development processes allows more appropriate definition of timelines and regulatory strategies.
- It is essential in CDx development not to think in terms of drug program vs. CDx program. When drug and CDx development are viewed as a single process with parallel aspects, the team can better identify the steps required to ensure that the CDx is ready in time for clinical trials and at drug launch. When drug and CDx development are viewed as separate processes executed individually, the likelihood increases that the processes will get out of sync and one process will have to wait on the other. Most obviously, if the IVD is not ready when the drug is, the pharmaceutical team may have to wait before moving forward with clinical trials. Think of it this way: Separate parallel processes will never converge. For CDx development to succeed, two usually distinct processes must converge.
- Finally, speaking from experience, it is important that both organizations involved in the development of the drug and CDx commit to honest and open communications. As research is done in the real world, unexpected challenges and delays will arise. When they do, it is important to inform all parties so that all can plan accordingly.
In the midst of a CDx project, it is also important to remember what a leap such a project represents over development of drugs for catch-all indications defined around symptoms and disease effects rather than mechanisms. Simultaneous availability of drug and CDx makes it much easier to select appropriate subjects for clinical trials and demonstrate efficacy in smaller populations. This greatly improves the likelihood of timely regulatory approval. More importantly, it means the drug and CDx together, once approved and prescribed, will often deliver substantial treatment benefits. Coordinating drug and CDx development presents challenges, but the result justifies the effort.
Lynellen O’Donnell, BS, MBA/HCM, is a project manager at Health Decisions with extensive experience in IVD studies, including studies of companion diagnostics. In addition to 15 years of experience in clinical research, Lynellen has 8 years of experience as a medical technologist in hospital laboratories.