Drug-Diagnostic Co-Development in Cancer

Abstract

Within oncology, companion diagnostics are considered to be of important value as the efficacy rates of anticancer pharmacotherapy in many cases remain low. Both the costs and the consequences of treatment failure are significant. Drug-diagnostic combinations have been known for several decades within oncology and the preselection of patients based on the differences in their biology was practiced as early as the 1970s. In relation to the development of the first companion diagnostic (for the selective estrogen receptor modulator, tamoxifen), an increased efficacy rate was shown in patients identified as expressing high levels of the targeted estrogen receptor. Another drug-diagnostic combination within oncology — the humanized monoclonal antibody trastuzumab targeting the human epidermal growth factor receptor 2 (HER2) and the immunohistochemical HER2 assay — has become a model for the co-development of a drug and companion diagnostic. In this co-development process, the companion diagnostic development stages closely align to the drug development phases, passing through a Prototype Assay stage, an Analytically Validated Assay stage and ending up as a Clinically Validated Assay. The obvious outcomes of drug-diagnostic co-developments are more effective drugs and hopefully also reduced numbers of patients in the controlled clinical trials. Typically, at least two independent, randomized, phase III trials, both displaying positive results over the current standard treatment, have been applied as a standard for regulatory approval. However, by incorporating companion diagnostics in the clinical trial designs, the numbers of patients in these studies will decrease. The variability in the pathophysiology of the patients will be reflected, and this information is used to identify those patients that are likely to respond to the targeted drug and thereby validate the clinical utility of the companion diagnostic. Studies designed to assess both a diagnostic and a drug can be based on both prospective and retrospective designs. The targeted clinical trial design allows for an increased success rate in the individual drug-diagnostic co-developments by reducing the failure rate, which in turn will reduce development costs and time, and hence increase the probability of therapeutic and registration success. Drug approval authorities such as the US FDA, European Medicines Agency and the State Food and Drug Administration in Japan, are also encouraging greater use of companion diagnostics for drug development. The drug-diagnostic co-development model will be the preferred future way to develop new targeted anti-cancer drugs, which will be to great benefit for the cancer patients.