ST-605 is an ophthalmic gel formulation of ganciclovir (GCV), which was developed by Laboratoires Thea, a specialist ophthalmic drug company in France. ST-605 is currently marketed in Europe and USA for the treatment of acute superficial herpetic keratitis. In Japan, we will develop ST-605 first for the treatment of cytomegalovirus (CMV) infection of anterior ocular tissues.
GCV is an anti-viral compound discovered in 1980s. While GCV has a strong anti-viral effect against herpes simplex viruses, it is often not used due to adverse events such as bone marrow toxicity. Despite this, GCV is used to treat CMV infection as other anti-viral drugs do not show strong suppressive effects on this virus. Indeed, GCV is the most prescribed anti-CMV drug in the world.
CMV sometimes causes inflammation in various organs in patients with impaired immune systems. In ocular tissues, it is well known to cause retinitis in AIDS patients. On the other hand, CMV infection of the anterior chamber was not recognized until recently. In 2006, Drs. Kinoshita and Koizumi from the Kyoto Prefectural University of Medicine reported for the first time that CMV caused corneal endothelialitis. Since then, CMV infection of anterior ocular tissues, such as the iris and ciliary muscles, has been reported. This CMV-induced endothelialitis is not cured spontaneously, and once inflammation occurs in corneal endothelial cells, the symptoms will become increasingly worse, eventually causing blindness. It should also be noted that even if CMV is suppressed by GCV, stopping the medication sometimes allows viral re-proliferation and subsequent inflammation. Thus, CMV ocular infection is a serious disease. At present, systemic administration of GCV is the only effective remedy for CMV-induced ocular inflammation and a topically applicable eye-drop formulation of GCV is required.
Currently, an investigator-sponsored pilot clinical study of ST-605 is ongoing in Japan. Although the total number of cases is less than 10, we have observed quite good efficacy in all cases examined.
We have already finished discussion with PMDA (Pharmaceuticals and Medical Devices Agency of Japan) about the development of ST-605 and almost fixed the design of the clinical trials for the approval of the drug. We plan to file NDA for the indication of CMV infection around the end of 2017 and expect to get the approval of ST-605 marketing in 2018. Since ST-605 is used for the treatment of herpetic keratitis in many countries, we intend to extend the indication of ST-605 for herpetic keratitis in Japan.