Pharmacodynamic efficacy of second-generation intravitreal axitinib implant (Axpaxli™) in a VEGF challenge rabbit model

Abstract

Purpose : Axitinib intravitreal implant (AXPAXLI™), utilizing a bioresorbable hydrogel platform (ELUTYX™), is designed to deliver axitinib for 9-12 months and the first generation (Gen1) 600 µg dose was evaluated in wet age-related macular degeneration clinical trials and diabetic retinopathy. A second-generation (Gen2) implant was developed to synchronize the hydrogel durability with delivery of the total axitinib dose while maintaining the daily release rate. This study evaluates the pharmacodynamic efficacy of the optimized Gen2 450 µg axitinib intravitreal implant.

Methods : Dutch-belted rabbits received bilateral intravitreal injections (IVT) of Gen2 450 µg axitinib implants and were compared against untreated controls and bevacizumab-treated eyes. To evaluate efficacy, 1 µg vascular endothelial growth factor (VEGF) was administered IVT repeatedly to induce retinal blood vessel leakage which was quantified by fluorescein angiography and scored on a scale from 0-4 throughout the study. In progress study results up to 73 days are reported and the study duration is planned for 90 days.

Results : The axitinib implant substantially reduced retinal vessel leakage following dosing compared to untreated controls. The implants group maintained low leakage scores (mean: 1.0 to 1.8) throughout this period, while controls exhibited increased tortuosity and leakage (mean: 3.2 to 4.0). Bevacizumab-treated eyes showed no vascular leakage for up to 31 days (mean: 0.0), after which effectiveness waned. At 73 days, the axitinib implant continued to suppress vascular leakage effectively (mean: 1.0), whereas the bevacizumab group showed similar leakage scores (mean 3.7) to untreated eyes (mean 3.5). There were no implant-related effects on clinical observations through 73 days.

Conclusions : Gen2 450 µg axitinib intravitreal implant showed a sustained pharmacodynamic effect for at least 73 days, surpassing the duration of bevacizumab’s effectiveness. These findings up to 73 days demonstrate axitinib intravitreal implant’s steady inhibition of VEGF activity through repeat challenges and potential to continuously control retinal vascular diseases. We anticipate reporting additional results from this ongoing study.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.