A Growing List of Advantages
Companion diagnostics confer multiple benefits to drug development because they are able to identify patients more likely to respond to a targeted drug, which in concept delivers the right drug to the right patient at the right time.
One advantage includes the increased likelihood of meeting primary endpoints, as efficacy is more likely to be demonstrated in the targeted, “biomarker positive” patient population. This approach leads to the greater probability of regulatory approval and payor reimbursement. In addition, smaller and more streamlined clinical trials in the targeted patient population may be conducted, an approach that can lead to decreased development timelines and conserved resources.
While the development of a companion diagnostic is frequently not initiated until a drug has reached later stages of development, pursuing early development of these tests, even preclinically, is also advantageous because it enables the validity of the biomarker target to be determined before significant resources have been invested, increasing the likelihood of development success.
Two examples showing the benefits of early adoption of companion diagnostics are the early FDA approvals of Roche’s Zelboraf® (vemurafenib), and Pfizer’s Xalkori® (crizotinib), both of which are targeted drugs with companion diagnostics. These therapeutics reached the market in less than five years from entering the clinic, an impressive feat that was attributed to the early adoption of the companion diagnostics. In both cases the biology of the biomarker target was well understood, which also enabled the companion diagnostic to initiate earlier in development. Also, in each case, the use of a companion test generated impressive data, with Roche’s Phase III study being halted early because of strong efficacy, and Zelboraf gaining subsequent approval based on these positive results. Pfizer’s Xalkori, along with its companion diagnostic, received conditional approval from the FDA based on data from two single-arm studies, including a Phase II trial and an expansion cohort of a Phase I study.
The early adoption of a companion diagnostic also allows certain important properties about a therapeutic target to be confirmed, including levels of its expression in specific cancers as well as its ability to functionally bind a clinical drug candidate. Each of these properties affects the safety and efficacy of the targeted drug; thus, obtaining this information early in development is useful for determining development priorities, including whether the clinical candidate will advance.
Historically, the dominant business model for developing companion diagnostics has been for a biopharma company to partner with a diagnostics firm; however, the development process may be streamlined through the use of in-house capabilities to co-develop these tests. This is especially true as early drug discovery efforts typically yield applicable information for the development of the companion diagnostic, which potentially improves success and shortens time to market.