Long-term safety of repeated intravitreal axitinib implant (Axpaxli™) administrations in non-human primates

Abstract

Purpose : The safety of repeated dosing is crucial for chronic retinal vascular conditions as they often necessitate prolonged treatment regimens. Intravitreal axitinib implant (AXPAXLI™), an investigational therapy for wet age-related macular degeneration and diabetic retinopathy, was designed to continuously control disease activity by releasing a potent tyrosine kinase inhibitor for 9-12 months. This study aimed to investigate the preclinical safety of the first-generation (Gen1) intravitreal axitinib implant when administered repeatedly every 6 months in non-human primates.

Methods : Cynomolgus monkeys were administered two Gen1 700 µg axitinib implants initially, followed by a single Gen1 700 µg implant at 6 and 12 months. The 18-month study included ophthalmic evaluations, intraocular pressure (IOP) measurements, ocular scoring, optical coherence tomography (OCT), confocal scanning laser ophthalmoscopy (cSLO), electroretinography (ERG), bioanalysis, and clinical pathology.

Results : No systemic effects related to the axitinib implant or its repeated dosing were observed, as indicated by clinical observations, body weight, clinical pathology, and macroscopic pathology endpoints. Ophthalmic assessments showed no clinically significant changes in IOP, cSLO, OCT, or ERG following repeat dosing every 6 months. Plasma samples revealed minimal to no systemic exposure over the study duration.

Conclusions : Repeated intravitreal administration of axitinib implants in a nonclinical primate model was observed to be generally well-tolerated over an 18-month period. This study establishes the no observed adverse effect level for the axitinib implant at two 700µg implants (1400 µg). These findings reinforce the sustained release of axitinib from an intravitreal implant as a potential therapeutic option for the treatment of retinal vascular diseases.

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