Diquafosol: DE 089, diquafosol tetrasodium, INS 365, INS 365 Ophthalmic, INS 365 Respiratory, KPY 998.

Abstract

Diquafosol [INS 365, KPY 998, diquafosol tetrasodium, DE 089, INS 365 Respiratory, INS 365 Ophthalmic] is a mucolytic compound that stimulates mucociliary clearance and also hydrates the mucosal surface of the lung. It is an activator of the P2Y2 receptor, which appears to be a key regulator of mucociliary clearance. Unlike the earlier P2Y2 receptor agonists such as uridine 5'-triphosphate, diquafosol is very stable chemically and does not require refrigeration or special handling. This makes diquafosol suitable for the treatment of chronic conditions. Diquafosol was originally developed at the University of North Carolina in the US. In September 2003, the US FDA announced that it accepted Inspire Pharmaceuticals' NDA filing for diquafosol tetrasodium ophthalmic solution for the treatment of dry eye. Additionally, FDA has completed a preliminary review of the NDA and issued the Filing Review Letter stating that no potential filing review issues were found during the review period. Inspire Pharmaceuticals' NDA for diquafosol has been granted priority review status, with initial FDA action expected at a target of 6 months after NDA submission. The first launch of diquafosol could potentially occur in the first quarter of 2004. Previously in January 2002, preliminary results from one of the US trials (study 104) revealed that the primary efficacy objectives of the study were not met. Data were re-evaluated and resubmitted in March 2002. Inspire Pharmaceuticals received a milestone payment from Allergan, which was not dependent on the study outcome, following the completion of study 104 and the submission of these study data. Phase II trials of diquafosol for dry eye are being conducted in Japan by Santen Pharmaceuticals. Santen projects that the compound will be launched in Japan during 2008-9. Phase I trials are also being conducted in the UK. Diquafosol eye drops activate P2Y2 receptors on the surface of the eye and inner eyelids, enhancing the natural process of tear secretion. Stimulation of tear secretion with diquafosol causes the release of salt, water, mucin and other components of the tear film, resulting in hydration of the surface of the eye. As there are no approved pharmacological therapies for dry eye, diquafosol is a potential breakthrough treatment for this disorder.