The efficacy evaluation study of the clinical eye drop formulation of the NOX inhibitor, SJP1804 and the design of a phase 1 clinical trial for the treatment of wet AMD.

Abstract

Purpose : The repeated invasive intravitreal (IVT) injections and the presence of poor responders of the VEGF blocking agent, the currently only available treatment for wAMD, have raised the need for less invasive dosage and drugs of new mechanism. We previously showed the superior/equivalent efficacy of the non-invasive eye drop of the NOX inhibitor compared to aflibercept (IVT) in CNV animal models. In this study, the eye drop SJP1804 containing 0.25% API was optimized for clinical application and the efficacy of the clinical formulation of SJP1804 for wAMD was evaluated using the mouse and rabbit CNV models.

Methods : SJP1804 (0.25% API) was administered (3 or 6 times/day, which corresponds to 1~3 times/day in human based on human equivalent dose and intraocular PK of the experimental animals) via eye drop for 15 days and 56 days, respectively, in mouse and rabbit CNV models. Additionally, combination therapy of SJP1804 (3 or 6 time/day) and aflibercept (2 mg/eye IVT) was also treated in rabbits. The CNV lesions in both animal models were measured by angiography. And the concentration of API in the rabbit retina/choroid after administration of the SJP1804 was determined by LC-MS/MS.

Results : In both mouse and rabbit CNV models, 3 or 6 times daily eye drops of SJP1804 (0.25% API) significantly reduced the CNV lesions. In details, 3 times daily eye drop of SJP1804 showed equivalent efficacy and 6 times daily eye drop of SJP1804 showed superior CNV lesion reduction compared to 2 mg/eye aflibercept in the rabbit CNV models. Moreover, 3 or 6 times daily eye drops of SJP1804 complemented the weak therapeutic effects of 2 mg of aflibercept in this model. And the data from LC-MS/MS suggested that the drug in eye drop reached to the target region through the trans-sclera pathway.

Conclusions : Taken together, the results showed that excellent efficacy of the clinical eye drop formulation of SJP1804 (0.25% API) in CNV. Considering the fact that the intraocular half-life of various drugs in human is about 2.5 times longer than that in rabbit, it is supposed that 1~3 times/day administration of SJP1804 eye drop is sufficient to exert clinical efficacy. Based on the results, we further designed phase 1 clinical trial of SJP1804 (0.25% API) eye drop in health Korean and Caucasian male subjects for investigating PK, safety and local tolerability.

This is a 2021 ARVO Annual Meeting abstract.