Purchase this article with an account.
Kyeongjin Ahn, Hyo-Won Song, Eunhye Jo, Jin Cheul Kim, Soo Jin Lee, Sung Hwan Moon, Min Hyo Ki; SJP1803 implant, the long-term delivery formulation of a novel small molecule NADPH oxidase inhibitor, for the treatment of wet AMD. Invest. Ophthalmol. Vis. Sci. 2020;61(7):1794.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Wet age-related macular degeneration (wAMD) is a chronic, degenerative eye disease leading to progressive loss of vision. Current standard therapy of wAMD requires frequent intravitreal (IVT) injections thus results in poor patient compliance. NADPH oxidase (NOX) has been known to promote both development and progression of wAMD. This study evaluates in vitro effects and in vivo efficacy of a novel NOX inhibitor, SJP1803 (APX-1004F). SJP1803 implant, a formulation for long-term delivery, was designed to minimize the frequency of IVT injection, and pharmacokinetics (PK) of SJP1803 implant was studied.
The inhibition activities of each NOX isoform by SJP1803 and its off-target profiles were assessed. The in vitro effects of SJP1803 on VEGF expression in human retinal pigment epithelial cells (ARPE-19) and tube-formation in human retinal microvascular endothelial cells (HRMEC) were analyzed. The efficacies of SJP1803 administered via IVT injection were tested in comparison with aflibercept as a positive control in the mouse model of laser-induced choroidal neovascularization. Fundus fluorescein angiography (FFA), optical coherence tomography (OCT) and electroretinography (ERG) were performed to evaluate the efficacy of SJP1803. SJP1803 implant was formulated for long-term delivery and the PK parameters of the SJP1803 IVT injection and SJP1803 implant were measured.
SJP1803 selectively inhibited NOX activities without inhibition of other oxidases and without affecting any other enzymes or receptors in off-target profiling panels. SJP1803 reduced the VEGF expression stimulated by high glucose in ARPE-19 cells and VEGF-induced tube formation in HRMECs, suggesting the anti-angiogenic effects of SJP1803. 0.3μg of SJP1803 IVT injection showed equivalent efficacy to 20μg of aflibercept on FFA, OCT and ERG. SJP1803 implant showed prolonged release up to 3 months in rabbits, equivalent to 6 months in human, while IVT injection of SJP1803 only lasted 72 hours in mice.
This study demonstrated the in vitro anti-angiogenic effects of SJP1803 and proved that IVT injection of SJP1803 showed equivalent efficacy to the commercial drug, aflibercept. Finally, PK results in rabbits suggest SJP1803 can be a potentially less invasive therapeutic drug via an implant formulation leading to improved patient compliance in the treatment of wAMD.
This is a 2020 ARVO Annual Meeting abstract.
This PDF is available to Subscribers Only