A 6-Month GLP Toxicology Study of a Novel Hydrogel-based, Axitinib Intravitreal Implant (OTX-TKI) in Non-Human Primates

Abstract

Purpose : Neovascular retinal diseases may be responsive to tyrosine kinase inhibitors (TKIs) which have a broader anti-angiogenic profile than anti-vascular endothelial growth factor agents alone. OTX-TKI is a novel, hydrogel-based, biodegradable, intravitreal implant designed to deliver the TKI axitinib for up to 6-9 months for the treatment of neovascular retinal diseases. The purpose was to evaluate the toxicology profile of OTX-TKI for 6 months in non-human primates (NHP).

Methods : Six cynomolgus monkeys were injected intravitreally with an OTX-TKI 700 µg implant in the right eye and saline in the left eye (control). Experimental dose represents a human equivalent dose of 1400 µg axitinib and 2.3x ocular dose safety margin when normalized to the vitreous volume between human and monkey. Ophthalmic exams with slit lamp biomicroscopy, intraocular pressure (IOP), optical coherence tomography (OCT) and confocal scanning laser ophthalmoscopy (cSLO) images were collected throughout the 6-month study period.

Results : Aqueous cell and flare, and vitreous cell and haze were graded a score of 0 at all timepoints through 6-months in all OTX-TKI and control eyes. No abnormalities were observed by ophthalmic exams. No clinically significant differences in IOP were observed between OTX-TKI and control eyes through 6-months. OCT imaging showed no clinically significant changes. Implants appeared idle and fully visible in the inferior vitreous up to 5-months. At Month 6, cSLO images showed implants in a majority of animals (4/6) had completely degraded and the implants in the remaining two animals were beginning to degrade.

Conclusions : OTX-TKI was generally well-tolerated with a favorable safety profile following administration in NHPs. No signs of intraocular inflammation or clinically significant changes in IOP and OCT images were observed. The safety and efficacy of OTX-TKI 600 µg intravitreal implant is currently being evaluated in humans for the treatment of wet age-related macular degeneration in a U.S.-based Phase 1b study.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

 

Confocal scanning laser ophthalmoscopy (cSLO) show implant biodegradation around Month 6