U.S. Phase 1 Study of Intravitreal Axitinib Implant (OTX-TKI) for Neovascular Age-related Macular Degeneration

Abstract

Purpose : OTX-TKI is a novel, bioresorbable, hydrogel implant designed to deliver a potent tyrosine kinase inhibitor, axitinib, for 6 or more months and can potentially address challenges with current anti-VEGF therapy for neovascular age-related macular degeneration (nAMD). The study was designed to assess the safety, tolerability, and biological activity of a single OTX-TKI implant in nAMD patients.

Methods : Randomized, controlled, double-masked, multicenter, Phase 1 clinical trial in the United States. Neovascular AMD adult subjects who were previously treated with anti-VEGF intravitreal injections and were free of excess intraretinal and subretinal fluid were included in the study. Subjects were randomized 3:1 to receive either a single OTX-TKI 600µg implant on Day 0 and aflibercept 2mg at Month 1, or aflibercept 2mg Q8W. Incidence and severity of adverse events (AEs), changes in visual acuity (BCVA using ETDRS letters), central subfield thickness, and number of rescue injections (supplemental anti-VEGF injections) were assessed.

Results : The study enrolled 21 subjects (n=16 for OTX-TKI and n=5 for aflibercept). OTX-TKI was well tolerated with no reports of drug-related ocular or systemic serious AEs were reported in either group. Following dosing with OTX-TKI, BCVA and CSFT remained stable for at least 7 months with minimal changes from baseline. At Month 7, mean change in BCVA for OTX-TKI and aflibercept (-1.3 and -1.0 letters, respectively) and mean change in CSFT for OTX-TKI and aflibercept (+9.2 and +0.4 µm, respectively) were comparable. Eighty percent (80%) of OTX-TKI subjects did not receive rescue therapy for up to 7 months.

Conclusions : In this 7-month interim analysis, OTX-TKI produced a stable and sustained effect on BCVA and CSFT that was comparable to nAMD standard of care aflibercept Q8W. OTX-TKI was generally well tolerated with a favorable profile. The study is ongoing and follow-up continues to Month 12.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.