Companion diagnostics—a tool to improve pharmacotherapy

Abstract

The variability of pharmacotherapy can be of a significant magnitude, and the main reason for this is often diseases heterogeneity. Patients who have similar diagnoses very often respond differently to the same pharmacological intervention, with great variability in both efficacy and safety outcome. Despite having discussed personalized medicine for more than a decade, we still see that most drug prescriptions for severe chronic diseases are largely based on 'trial and error' and not on solid biomarker data. However, with the advance of molecular diagnostics and a subsequent increased understanding of disease mechanisms, things are slowly changing. Within the last few years, we have seen an increasing number of predictive biomarker assays being developed to guide the use of targeted cancer drugs. This type of assay is called companion diagnostics and is developed in parallel to the drug using the drug-diagnostic co-development model. The development of companion diagnostics is a relatively new discipline and in this review, different aspects will be discussed including clinical and regulatory issues.Furthermore, examples of drugs, such as the ALK and PD-1/PD-L1 inhibitors, that have been approved recently together with a companion or complimentary diagnostic will be given.

Composite iron oxide–Prussian blue nanoparticles for magnetically guided T₁-weighted magnetic resonance imaging and photothermal therapy of tumors

“…1 A well-known example of a commercialized theranostic is the use of HercepTest ® (Agilent, Santa Clara, CA, USA) in combination with Herceptin ® (Genentech, South San Francisco, CA, USA) for treating breast cancer. 2 However, this approach requires the sequential administration of the paired Dx/Rx agents. A more desirable and potentially straightforward approach would be the simultaneous administration of the Dx/Rx agents to shorten procedure times while potentially improving patient comfort.…”

Clinical and Regulatory Aspects of Companion Diagnostic Development in Oncology

“…In a phase II study conducted with tamoxifen, a high correlation between a positive estrogen receptor status and response to the treatment was observed. Based on this finding the investigators suggested that the estrogen receptor assay should be used as a means to select patients for treatment with tamoxifen . Despite that this phase II study showed the significance of combining drug and diagnostics, it was not until the end of the 1990s that the first companion diagnostic obtained regulatory approval .…”

“…Based on this finding the investigators suggested that the estrogen receptor assay should be used as a means to select patients for treatment with tamoxifen . Despite that this phase II study showed the significance of combining drug and diagnostics, it was not until the end of the 1990s that the first companion diagnostic obtained regulatory approval . Here the US‐based biotech company, Genentech (South San Francisco, CA), developed trastuzumab (Herceptin, Roche/Genentech) for the treatment of human epidermal growth factor receptor 2 (HER2)‐positive metastatic breast cancer.…”

“…Especially within oncology, the more mechanistic driven drug‐diagnostic codevelopment model has replaced the traditional all‐comers approach, which has also greatly influenced the trial designs used during the clinical development . Drugs are now being developed for molecular defined subsets of patients, and here, molecular diagnostic plays a significant role and has become an integrated part of the development process . The individual steps in the traditional parallel drug‐diagnostic codevelopment model are shown in Figure .…”

Serum Heparin-binding Epidermal Growth Factor-like Growth Factor (HB-EGF) as a Biomarker for Primary Ovarian Cancer

“…However, identifying patients who would benefit from bevacizumab therapy has been challenging, particularly because there are no companion diagnostics for monitoring or predicingt response to treatment. To date, pharmacotherapy for ovarian cancer has had variable success (13). As a result, there is an urgent need to develop novel targeted agents as well as companion diagnostics for cancer therapy.…”