The combination of increased R&D efforts in targeted therapies and the high failure rates in late stage trials will soon change the endpoints of early phase trials. The major change will be to focus more on proof-of-mechanism and proof-of-concept studies, in addition to safety and dose finding analysis. The ability to confirm that a drug has a viable chance of reducing symptoms or modifying disease ensures that only the most promising drugs will proceed through the development cycle. Furthermore, the removal of poorly performing compounds early on will potentially reduce R&D costs.
Imaging, particularly molecular imaging, has proven to be very effective in small phase 0/1 studies when revealing the effects of therapies at the target site. In CNS indications, for example, receptor occupancy and displacement studies have been used successfully to reveal pharmacodynamics and target effectiveness. With the increased use of personalised medicine approaches in oncological trials, researchers can obtain insight into the effects at the tumour receptor level and incorporate the efficacy measurements of tumour volume and metabolic activity to aid in making go/no-go decisions.
One of imaging’s greatest assets is the ability to use a wide variety of tools and imaging techniques to identify potential biomarkers. Imaging not only allows for the measurement and analysis of efficacy, biodistribution, and proof-of-targeting, but can also assist in patient stratification. The ability to identify those patients who will benefit most from a late phase trial helps conduct future trials more effectively. An enhanced early phase study also allows for validation of a new biomarker in parallel for use in your phase III trial and ensures optimal biomarker selection for your pivotal trial.