Objective

There is a desperate need for highly efficacious novel analgesics which do not suffer the unwanted side effects of existing treatments. Peripherally expressed sodium channels such as the Nav1.3, Nav1.7, Nav1.8 and Nav1.9 subtypes have long been considered compelling analgesic targets. In particular, the elucidation of a link between genotypic changes in Nav1.7 and the clinical phenotypes of congenital insensitivity to pain as well as inherited erythromylalgia has led to a significant interest into the potential utility of Nav1.7 blockers for the treatment of pain. Despite intense efforts and innovative precision medicine approaches, the potential of the first generation of Nav1.7 selective blockers such as PF-05089771 remains largely unfulfilled. The presentation will focus on the current status of Nav1.7 blockers in development, clinical data generated to date, challenges presented by the limitations in the understanding of the underlying biology and future opportunities to develop the next generation of Nav1.7 selective blockers.